EP2432580A2

EP2432580A2 - Method for producing nanoparticles using miniemulsions

Info

Publication number: EP2432580A2
Application number: EP10721743A
Authority: EP
Inventors: Bernd Sachweh; Sonja Judat; Thomas Danner; Robert Engel; Caroline Mages-Sauter; Heike Schuchmann; Marion Gedrat
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 2009-05-18
Filing date: 2010-05-10
Publication date: 2012-03-28
Also published as: US8512665B2; WO2010133465A2; WO2010133465A3; CN102438738A; CN102438738B; US20120063992A1

Abstract

The invention relates to a method for producing nanoparticles or nanostructured particles using a two-emulsion method, wherein particles are generated by the targeted coalescence of miniemulsions in a high-pressure homogenizer.

Description

Process for the preparation of nanoparticles using mini-emulsions

description

The present invention relates to a method for producing nanoparticles and / or nanostructured particles by means of an emulsion method, wherein particles are produced by targeted coalescence of at least two mini-emulsions.

The prior art discloses a multiplicity of production processes and uses of nanoparticles, it being possible to refer to nanoparticles as solid or colloidal particles having a particle diameter of less than 1 μm. Nanoparticles may be constructed, for example, of inorganic or polymeric material. They have in many cases an average particle size of 1 to 1000 nm. For the production of inorganic particles, e.g. the sol-gel process and the micro-emulsion technique known. Polymeric nanoparticles may e.g. be prepared by emulsion polymerization. The targeted formation and structuring of nanoparticles is of particular interest in order to achieve special properties of nanoparticles for highly specialized applications.

Emulsions are finely divided mixtures of at least two liquids which are not homogeneously miscible with one another. An example is the mixture of oil and water. A liquid forms the so-called inner or disperse phase (also disperse phase), which is distributed in the form of small droplets in the second liquid, the so-called outer or continuous phase. Important constituents of emulsions are surface-active substances, so-called surfactants or emulsifiers, which facilitate the formation of the droplets and counteract demixing (phase separation). A distinction is made between oil-in-water emulsions (O / W emulsion) in which droplets of the non-polar phase (for example oil droplets) are present in the continuous polar phase (for example water phase) and correspondingly water-in-oil emulsions (W / O). O emulsion), which are also called inverse emulsions. Emulsions are most likely to remain stable for a period of time and under certain conditions (e.g., temperature, pH range).

In conventional emulsions (macroemulsions) the drop sizes of the disperse phase are uneven. The droplet sizes in macroemulsions are usually between 100 nm and 1 mm. Macro emulsions are thermodynamically unstable and often segregate within a relatively short time. The term mini-emulsion refers to a thermodynamically unstable emulsion, wherein the disperse phase is present in very finely divided droplets with an average droplet diameter of <10 .mu.m, in particular <5 .mu.m. Mini-emulsions are obtained, for example, by shearing with a high energy input, starting from two (or more) immiscible liquids and one or more surfactants (surfactant, emulsifier). The droplets of a mini-emulsion can under certain conditions be kept stable for a certain period of time, so that the production of particles in mini-emulsions can take place by the fusion of different droplets. The required energy input (for example in a shearing process) for the production of mini-emulsions can be carried out, for example, by ultrasound treatment or by using a high-pressure homogenizer. Accordingly, mini-emulsions are described in which a solid, for example in the form of nanoparticles, is contained in the disperse phase as mini-suspoemulsions.

Thermodynamically stable emulsions, which are a special case and exist only in special composition ranges in the phase system water-oil emulsifier, are referred to as micro-emulsions. They form spontaneously and often appear transparent. They usually contain a high proportion of surfactant and also usually another surfactant, a co-surfactant. If two micro-emulsions mixed with different reactants in the disperse phase, it comes to a mass transfer between the disperse phases and thus to the reaction without the emulsion drops must be coalesced with energy input.

Mini-emulsion processes for the construction of structured nanoparticles, for example with a core-shell structure, are described in the prior art. The publication by K. Landfester (Adv. Mater. 2001, 13, No.10, 17.05.2001) describes the preparation of mini-emulsions and the use of mini-emulsions in the synthesis of nanoparticles and encapsulated nanoparticles. The synthesis of nanoparticles can be carried out, for example, with the aid of miniemulgierten molten salts or via the polymerization of a miniemulgierten monomer. However, a possibility for the targeted coalescence of mini-emulsion drops is not described. Disadvantage of the method described here is that each drop is transformed into a particle, whereby the drop size has a significantly limiting effect on the size of the resulting particles. WO 2008/058958 describes the preparation of core-shell particles, wherein an outer layer is applied to solid nanoparticles dispersed in a mini-suspoemulsion, by applying an emulsion in the dispersed (preferably aqueous) emulsion in an emulsion process with an emulsion. Phase dissolved precursor substance is converted in the disperse phase and thus applied to the dispersed nanoparticles. The preparation of spherical inorganic nanoparticles by precipitation in a 2-emulsion method using microemulsions is known. Lee et al. (J. European Ceramic Society, 19, 1999) describes the preparation of spherical ZrC> ₂ microparticles wherein two inverse microemulsions containing precursors or reactants in the aqueous dispersed phase are mixed and reacted.

The coalescence of mini-emulsions induced by ultrasound treatment or rotor-stator systems (Ultra-Turrax) described in the prior art has the disadvantage that the coalescence of the emulsion droplets can not be controlled. In addition, ultrasonic treatment is rather unsuitable for large-scale application because the ultrasonic method is difficult to handle for large-scale industrial processes. The effect of ultrasound is usually local and often results in bimodal particle size distributions. The use of micro-emulsions is limited to narrow special cases and also has the disadvantage that high amounts of surfactant and cosurfactant contaminate the resulting product.

It is an object of the invention to provide an easy-to-handle method for the targeted assembly of nanoparticles, and in particular of structured nanoparticles, wherein drops of a mini-emulsion are coalesced in a targeted manner and the coalesced droplets are used as reaction space (quasi as nanoreactor) ,

It has now surprisingly been found that mini-emulsions and mini-suspoemulsions can be prepared not only using a high-pressure homogenizer, but that mini-emulsions / mini-suspoemulsions or mixtures of different mini-emulsions / mini-suspoemulsions using a high-pressure homogenizer targeted to Coalescence can be performed. The droplets of the disperse phase of a mini-emulsion can be coalesced in a controlled manner if they are passed under high shear through (at least) one nozzle, for example a special homogenizing nozzle.

High-pressure homogenizers were originally developed for the homogenization of milk, in which the fat droplets of the milk are reduced to a mean drop diameter of 1 to 2 microns, so as to prevent the creaming of the milk. High-pressure homogenizers work according to the pressure relief system and consist essentially of a high-pressure pump and a homogenizing valve. High pressure homogenizers usually work in a pressure range of 100 to 1000 bar. The liquid flow generated by the high pressure pump (for example, a high pressure piston pump) flows through the homogenizer nozzle. Various embodiments of homogenizers and homogenizing nozzles are described in the prior art, such as flat nozzles, pinhole diaphragms, slit diaphragms, diverting nozzles, counter-jet dispersing agents. It is also possible to work with combinations of several identical or different homogenizing nozzles, whereby a back pressure is built up.

One possible embodiment of a homogenizing nozzle is the so-called flat nozzle. In the flat nozzle, the liquid flow flows through the valve seat and then radially through the homogenizing gap, which is only a few micrometers wide. The homogenizing gap is set by pressing a valve body onto the valve seat. The liquid exits the homogenizing nip at very high speed (e.g., about 300 m / s), impacts the baffle ring, and exits the valve via the outlet.

Other common embodiments of homogenizers include e.g. Two-jet nozzles or the combination of, for example, two pinhole diaphragms and the combination of pinhole with deflecting nozzles. Through a downstream pinhole or Umlenkdüse creates a back pressure, with the help of which the cavitation results can be influenced behind the first panel.

In the high-pressure homogenizer shear and expansion forces, impact flow and, to a significant extent, cavitation forces are effective. Cavitation refers to the formation and dissolution of cavities in liquids due to pressure fluctuations. The cavitation arises, for example, as a result of very fast moving objects in the liquid (for example propeller, stirrer) or by rapid movement of the liquid, for example through a nozzle, and by the action of ultrasound. Emulsifying pressure is the pressure drop across the homogenizing nozzle.

The present invention describes a process for the preparation of nanoparticles or nano-suspoemulsions which comprises at least two steps. In the following, the term "nanoparticles" also refers to nanoparticles which are present or are obtained in the form of a nanohuspoemulsion or nanosuspension.

A method for the production of nanoparticles in the context of the present invention comprises methods for the construction of nanoparticles and methods for nanostructuring of particles, in particular of nanoparticles. Nanostructuring comprises the production of a structure whose dimensions are in the size range of nanometers, such as, for example, the production of core-shell particles or the application of nanoscale regions to a particle surface, in particular a nanoparticle surface. In particular, a method for producing nanoparticles in the context of the present invention comprises a method for constructing nanoparticles, in particular from molecularly disperse-dissolved precursor substances.

The present invention relates to a process for the preparation of nanoparticles, wherein in a first step a) at least two mini-emulsions and / or mini-suspoemulsions are produced, each containing at least one reactant in the disperse phase and at least one emulsifier, and in one second step b) the mini-emulsions and / or mini-suspoemulsions thus produced are preferably mixed in a high-pressure homogenizer.

The production of the mini-emulsions and / or mini-suspoemulsions in step a) preferably takes place in a high-pressure homogenizer under an emulsifying pressure in the range from 200 to 1000 bar, particularly preferably in the range from 200 to 800 bar, more preferably in the range from 400 to 800 bar. But it is also possible to use mini-emulsions, which were prepared by another known method (for example by ultrasonic treatment).

In a preferred embodiment of the invention, the mixing of the mini-emulsions and / or mini-suspoemulsions in step b) takes place in a high-pressure homogenizer. In particular, the mixing in step b) takes place in a high-pressure homogenizer under an emulsifying pressure in the range from 100 to 1000 bar, preferably in the range from 400 to 1000 bar, particularly preferably in the range from 800 to 1000 bar.

The production of nanoparticles is carried out according to the method of the invention in particular by selectively coalescing the droplets of two mini-emulsions / mini-suspoemulsions with different disperse phases in which the reactants are present separately, the reactants being mixed and reacted. The droplet coalescence can be controlled in a targeted manner (for example by the design and combination of the nozzles or the nozzle geometry) according to the present invention, taking advantage of the phenomenon of the short instability of the emulsion droplets and the resulting drop coalescence after the homogenizing nozzle.

The process steps of the 2-emulsion method for particle generation initially involve the separate preparation of two mini-emulsions and / or mini-suspoemulsions (step a)), these starting mini-emulsions / mini-suspoemulsions preferably being in their disperse phases in terms of material differ. The targeted coalescence of the mini-emulsion droplets (or mini-suspoemulsion droplets) is effected in the second step (emulsification step (step b)). The reaction of the reactants in the coalesced droplets forms a solid, in particular in the form of nanoparticles or in the form of structures on already existing nanoparticles (eg to form a shell structure).

In order to convert the resulting mini-suspoemulsion into a nanosuspension, an amount of at least one of the emulsion phases can be removed in an optional step c); preferably, the disperse phase is removed; if appropriate, part of the continuous phase is also removed. This optional process step c) is preferably carried out by evaporation, e.g. by distillation.

The coalescence of the droplets by high-pressure homogenization (step b) can be determined, in particular, by varying the emulsification pressure, the geometry of the nozzle (s), the disperse phase fraction, the reactant concentrations, the temperature and the drop size distribution of the starting mini-emulsions or starting materials. Control mini-suspoemulsions.

The described mini-emulsions or mini-suspoemulsions may be O / W or W / O emulsions. Preference is given to using W / O emulsions (inverse emulsions). The continuous phases and the disperse phase of the two starting mini-emulsions / mini-suspoemulsions used as the main constituent preferably contain the same liquid, but they may also contain different liquids which are homogeneously miscible with one another.

The mini-emulsions and / or minisuspoemulsions are preferably W / O emulsions comprising an aqueous disperse phase. In particular, the mini-emulsions and / or minisuspoemulsions are W / O emulsions containing an aqueous disperse phase, in which in each case at least one reactant is dissolved. Preference is given to using non-polar, organic solvents or mixtures thereof as the continuous phase; in particular, the continuous phase is formed by alkanes.

In particular, W / O or O / W emulsions are used in the present invention containing an aqueous phase and a phase containing one or more organic solvents or monomers, these liquids are selected from the group C ₅ -C ₅₀ alkanes , vegetable and animal oils, silicone oils, paraffin, triglycerides, monomers (for example styrene, acrylates). In a preferred embodiment of the process described, the proportion of the disperse phase of the mini-emulsions and / or mini-suspoemulsions produced in step a), based on the total amount, is in the range from 1 to 70% by weight, in particular from 5 to 50% by weight. -%, preferably in the range of 20 to 40 wt .-%.

In one embodiment of the invention, the disperse and / or the continuous phase contain at least one emulsifier, wherein the emulsifier is preferably initially introduced in the continuous phase.

Depending on the system used, it is possible to use known anionic, cationic or nonionic emulsifiers for O / W and W / O emulsions. Emulsifiers for W / O emulsions usually have an HLB value of 3-8, emulsifiers for O / W emulsions usually have an HLB value of 8 to 18. The HLB value (of hydrophilic-lipophilic balance) represents a dimensionless number between 0 and 20, which makes statements about the water and oil solubility of a compound and plays an important role in the selection of emulsifiers or emulsifier mixtures.

It is preferred to add at least one emulsifier for W / O emulsions, which may be selected from:

Sorbitan fatty acid ester, such as SPAN ^® emulsifiers,

Lecithins and cholesterols,

Polysorbate, as TWEEN ^® emulsifiers,

Fatty acid ester of glycerol or polyglycerol esters, for example ^® Mazol emulsifiers fatty acid ester of polyethylene glycol or Etylenglykol

Amine alkoxylates, for example Quadrol ^® (BASF, DE),

Copolymers and block copolymers such as poloxamers (block copolymers of propylene oxide and E- thylenoxid, Pluronic ^®); Polyoxamines (block copolymers from

Ethylene oxide and propylene oxide with ethylenediamine block); Polyisobutene polyamine polymer (Glisopal ^®, BASF DE),

In a preferred embodiment, in steps a) and / or b) at least one W / O emulsifier added in the kontinulierlichen phases, which is selected from the group Glisopal ^® (BASF, DE), Quadrol ^® (BASF, DE), Pluronic ^® (BASF, DE), SPAN ^® emulsifiers, TWEEN ^® emulsifiers, Mazol ^® emulsifiers and lecithin.

If O / W mini-emulsions and / or mini-suspoemulsions are used, one or more known O / W emulsifiers can be used. Here are common non-ionic, anionic, cationic and ampholytic emulsifiers in question. The concentration of the emulsifier in the mini-emulsions or mini-suspoemulsions used is in the range from 0.1 to 10% by weight (based on the total emulsion), preferably in the range from 1 to 5% by weight, particularly preferably in the range of 1 to 3 wt .-%.

In particular, the mixing of the mini-emulsions and / or mini-suspoemulsions in step b) in a high-pressure homogenizer is effected by a homogenizing nozzle having a diameter in the range from 50 to 700 .mu.m, preferably 70 to 400 .mu.m. The preparation of the mini-emulsions and / or mini-suspoemulsions in step a) can likewise be carried out in the high-pressure homogenizer described above or in one of the embodiments described below.

Preferably, at least one homogenizing / homogenizing device selected from the group flat nozzle, perforated diaphragm, slit diaphragm, deflecting nozzle and counter jet disperser is used in the homogenizing steps a) and / or b). Particular preference is given to using at least one homogenizing nozzle / homogenizing device selected from the group consisting of the perforated diaphragm, slit diaphragm and deflecting nozzle in the homogenizing steps a) and b). In FIG. 2b, a perforated diaphragm with the diameter (hole diameter) d is shown schematically.

In a preferred embodiment of the invention, at least one two-jet nozzle is used in the homogenization steps a) and / or b). A two-jet nozzle comprises in particular a diaphragm with two bores which are mounted at a certain angle α to the diaphragm surface (see FIG. 2a). The liquid passes through the nozzle and is split into two jets of liquid which meet behind the bore exits. In particular, a two-jet nozzle having a diameter (hole diameter) d in the range of 50 to 700 .mu.m, preferably 50 to 100 .mu.m, and an angle α in the range of 10 ° to 60 °, preferably from 20 ° to 30 °, used. Figure 2a shows an embodiment of a suitable two-jet nozzle.

In one embodiment of the method according to the invention, the mixing of the mini-emulsions and / or mini-suspoemulsions under step b) takes place in a high-pressure homogenizer, wherein at least one two-jet nozzle with a diameter (hole diameter) d in the range of 50 to 700 microns and an angle α in the range of 10 ° to 60 ° is used as Homogenisierdüse.

In one embodiment of the method according to the invention, the mixing of the

Mini-emulsions and / or mini-suspoemulsions under step b) in a high pressure homogenizer, wherein at least one pinhole as a homogenizing with a Diameter (hole diameter) in the range of 50 to 700 microns, preferably 70 to 400 microns, is used. The mixing of the mini-emulsions and / or mini-suspoemulsions under step b) preferably takes place in a high-pressure homogenizer, wherein two pinhole diaphragms arranged one behind the other are used as the homogenizing nozzle, each having a diameter in the range from 50 to 700 μm.

In a preferred embodiment of the invention, one or more (preferably two) pinhole diaphragms having a diameter (hole diameter) in the range from 50 to 700 .mu.m, preferably 70 to 400 .mu.m, are used in the homogenization steps a) and / or b). Particularly preferred is a method in which the mixing of the mini-emulsions and / or mini-suspoemulsions under step b) takes place in a high-pressure homogenizer, wherein two successively arranged pinhole as homogenizer, each having a diameter in the range of 50 to 700 .mu.m, preferably 70 up to 400 μm.

In a further embodiment of the invention, two pinhole diaphragms with diameters of 100 μm and 200 μm are used. In a further embodiment, two pinhole diaphragms with diameters of 200 μm and 400 μm are used.

The size distribution of the droplets of an emulsion or suspoemulsion can be determined by conventional methods, for example by means of laser diffraction or dynamic light scattering.

A parameter of the droplet size distribution is the Sauter diameter. If the total volume of the emulsion droplets were to be transformed into spheres of equal size, the total surface area of the droplets remaining the same, these droplets would have the Sauter diameter (X _{1 2} ) as the diameter. It is defined by the following formula:

with the specific surface S _v = S _g esA / ge _S , where S _{tot is} the total surface area of the particles and V _{ges is} the total volume of the particles.

A reactant in the context of the present invention is a starting material for a chemical reaction or physical conversion which, for the purposes of the invention, leads to the formation or precipitation of a solid under the given conditions. For the purposes of the present invention, a precursor substance (precursor), which already has a similar structure as the product, can also be referred to as a reactant. It is also possible to react a reactant mixture which is present in one of the disperse phases by mixing it (with coalescence of the emulsion droplets) with a second disperse phase containing a suitable catalyst. Therefore, a reactant within the meaning of the present invention may also be understood to be a catalyst or another substance involved in a chemical reaction or physical conversion (such as an antisolvent).

A reaction within the meaning of the present invention is also understood to mean the precipitation of a dissolved precursor substance by mixing with an antisolvent or by a change in the pH.

The reactants are preferably dissolved in the disperse phase of a mini-emulsion, in particular molecularly disperse or colloidally dissolved. In a further embodiment of the invention, it is also possible to use solid reactants, for example in the form of nanoparticles, in the form of a mini-suspoemulsion in the present process according to the invention. The reaction of the reactants necessarily produces at least one solid product. The reactants can in particular be reacted with one another in a precipitation reaction, in a redox reaction, in an acid-base reaction or in a polymerization.

In one embodiment of the invention, the described method for producing nanoparticles is characterized in that the mini-emulsions or mini-suspoemulsions are W / O emulsions which contain an aqueous disperse phase in which in each case at least one Reactant is dissolved, in particular molecular disperse dissolved.

In one embodiment, the invention relates to a process for the preparation of nanoparticles, characterized in that the reactants contained in the disperse phases of the mini-emulsions and / or minisuspoemulsions are molecularly dispersed salts which are present in a molar concentration in the Range from 0.01 to 0.5 mol / l, and which react when mixing the mini-emulsions and / or mini-suspoemulsions in step b) to precipitate a solid.

Furthermore, at least one of the reactants contained in the disperse phases of the mini-emulsions and / or minisuspoemulsions can be an acid or a base. It is preferable that one of the reactants is an acid or a base, preferably in a concentration in the range of 0.01 to 1 mol / l. In particular, the reactants are a water-soluble salt containing cations selected from the group of alkali metal, alkaline earth metal, noble metal (gold (Au), silver (Ag), ruthenium (Ru), rhodium (Rh), palladium (Pd), osmium (Os), iridium (Ir), platinum (Pt)), silicon (Si), tin (Sn), iron (Fe), nickel (Ni), cobalt (Co), zinc (Zn), titanium (Ti), Zirconium (Zr), yttrium (Y) and cerium (Ce), particularly preferred are salts of alkali metal, alkaline earth metal and noble metal, further preferably salts of alkali metals.

With the aid of the process according to the invention, nanoparticles can preferably be prepared selected from the group consisting of barium sulfate nanoparticles, zinc oxide nanoparticles, titanium dioxide nanoparticles, tin oxide nanoparticles and silicon dioxide nanoparticles.

In one embodiment of the invention in the first step of the above-described process a) a miniemulsion containing as disperse phase an aqueous solution of a water-soluble barium salt (eg barium chloride) and a miniemulsion containing as disperse phase an aqueous solution of a water-soluble sulfate salt (eg Potassium sulfate), and in the second step, the miniemulsions are mixed in a high pressure homogenizer to produce barium sulfate nanoparticles.

In a further embodiment of the invention, in the first step of the process a) described above, a miniemulsion containing as disperse phase an aqueous solution of a water-soluble zinc salt (eg zinc sulfate) and a mini emulsion containing as disperse phase an aqueous solution of a base (eg caustic soda) and in the second step, the miniemulsions are mixed in a high pressure homogenizer to produce zinc oxide nanoparticles.

Here, water-soluble is to be understood as meaning a salt which has a solubility in water of> 10 g / l.

The process according to the invention can be operated batchwise, for example by carrying out steps a) and b) with a time offset in the same high-pressure homogenizer. However, it is also possible to operate the process for producing nanoparticles continuously without the combination of several high-pressure homogenizers. The mini-emulsions and / or mini-suspoemulsions obtained in step a) can optionally be mixed in an intermediate step initially with low shear, for example with a propeller stirrer, and then brought to coalescence in a high pressure homogenizer. However, it is also possible to combine the mini-emulsions and / or mini-suspoemulsions directly in the high-pressure homogenizer.

The temperature in carrying out the process steps is in the range of 0 ⁰ C to 200 ⁰ C, preferably in the range of 10 ⁰ C to 100 ⁰ C. In a preferred embodiment of the invention, the temperature is in the range of 20 ° C to 30 ° C ,

In addition, the present invention also relates to nanoparticles which can be prepared or prepared according to the method described above. The present invention also relates to nanostructured particles prepared according to the method described above, i. H. on particles that have a structure in the nanometer range (example, core-shell particles or nanoscale areas on the particle surface).

The present invention relates to nanoparticles which are preparable (or obtainable) by a process in which, in a first step a), two mini-emulsions and / or mini-suspoemulsions are produced, each of which contains at least one reactant the disperse phase and at least one emulsifier, and in a second step b) the mini-emulsions and / or mini-suspoemulsions thus produced are mixed in a high-pressure homogenizer.

The present invention preferably relates to nanoparticles having a mean particle diameter in the range from 1 to 1000 nm, preferably in the range from 10 to 500 nm, very particularly preferably in the range from 10 to 200 nm. The nanoparticles obtainable by the process according to the invention can have a high uniformity, in particular with regard to the particle size.

The nanoparticles can be used in the form of the directly formed mini-suspoemulsion or in the form of a nanosuspension, which can be obtained partially or almost completely by removing at least one phase of the emulsion phases. Preferably, the disperse phase becomes part, the disperse phase is almost completely removed, or the disperse phase is removed together with a continuous phase portion. Furthermore, the nanoparticles can also be used in solid form, as can be obtained by suitable processes, eg drying, spray-drying. The particles produced with the aid of the process described can be used, for example, as catalysts, it being possible for the catalyst to be present in defined regions of the nanoparticle surface. The particles can also serve as particulate starting material for organic photovoltaics (OPV) or as controlled release systems for pharmaceutical applications and crop protection. Below is a brief description of the drawings:

1 shows the cumulative distribution Q ₃ (x) of the droplet sizes x (in μm) before and after the homogenization (step b) for the mini-emulsions produced in Example 3 (with ► = after the first emulsification step; Emulsification step at Δp = 200 bar, o = after the second emulsification step at Δp = 400 bar, ▲ = after the second emulsification step at Δp = 600 bar, V = after the second eumulization step at Δp = 800 bar, M = after the second emulsifying step at Δp = 1000 bar).

In Figure 2a, the structure of a two-jet nozzle with the angle α and the hole diameter d is schematically illustrated. In FIG. 2b, a perforated diaphragm with the diameter (hole diameter) d is shown schematically.

FIG. 3 shows the cumulative distribution Q ₃ (x) of the droplet sizes x in μm after the first and second emulsifying step for the mini-emulsions produced in Example 7 (with ■ = after the first emulsifying step, o = after the second emulsifying step at Δp = 400 bar, ▲ = after the second emulsification step at Δp = 1000 bar).

FIG. 4 shows the cumulative distribution Q ₃ (x) of the droplet sizes x in μm after the first and second emulsification steps for the mini-emulsions produced in Example 8 (with ■ = after the first emulsification step; 0 = after the second emulsification step Δp = 1000 bar, standard pinhole d = 0.1 mm, ▲ = after the second emulsification step at Δp = 1000 bar, standard pinhole d = 0.2 mm, V = after the second emulsification step at Δp = 1000 bar, two-jet nozzle as described in Example 8).

The present invention will be further illustrated by the following examples.

Examples

Example 1 (preparation of the starting mini-emulsions in the emulsifying step a))

Barium chloride (BaCl ₂ , Merck, Darmstadt) and potassium sulfate (K ₂ SO ₄ , Merck, Darmstadt) were used as received and were subjected to no further purification. Barium chloride and potassium sulfate were dissolved in deionized water at the indicated molar concentration. In all experiments, the molar ratio b of the reactants according to equation (1) was about 5, so the reactant barium sulfate was always presented in 5-fold excess compared to potassium sulfate.

b = - ^C ^ - (1) so. As the emulsifier, the nonionic emulsifier Glissopal ^® EM-23 (BASF SE, Ludwigshafen, Germany) was added to the continuous phase. The emulsifier concentration was 3% by weight.

The aqueous solutions of BaCl ₂ and K ₂ SO ₄ were each mixed with n-decane. Before the actual high-pressure homogenization step, the mixtures thus obtained were stirred for 2 minutes with a propeller stirrer (diameter about 6 cm) at 400 min ^{-1 and} then the mixtures were separated in a high-pressure homogenizer (M-110 Y Microfluidizer® from Microfluidics). The "microfluidizer nozzle" from Microfluidics was used.

The two mini-emulsions obtained as described above were then mixed and stirred for two minutes (propeller stirrer, 400 rpm). The mini-emulsion thus obtained was used to prepare nano-suspoemulsions in Examples 3 to 6.

Example 2 (preparation of the starting mini-emulsions in step a) - influence of the emulsifying pressure)

The mini-emulsions were prepared as described in Example 1. The barium chloride concentration was C (BaCl ₂ ) = 0.10 mol / l and the potassium sulfate concentration C (K ₂ SO ₄ ) = 0.02 mol / l. The emulsifier concentration was 3 wt .-% in both emulsions, the disperse phase fraction 40 wt .-%. The reproducibility of the results was confirmed by repeated repetitions of the experiments.

The mixtures obtained were homogenized in each case at 400 and 800 bar emulsifying pressure as described in Example 1. Mean droplet sizes in the range of 0.5 to 1 μm were obtained. It was found that an emulsification pressure of Δp = 800 bar was particularly suitable for obtaining a stable miniemulsion containing barium chloride in the aqueous dispersed phase. For the potassium sulfate solution as the disperse phase (C (K ₂ SO ₄ ) = 0.02 mol / l), a homogenization pressure Δp = 400 bar resulted in a stable mini-emulsion. The Sauter diameter X _{1 2} here amount to about 365 nm for the emulsion with barium chloride solution and about 475 nm with potassium sulfate as the disperse phase.

Unless otherwise stated, the premix with barium chloride solution at Δp = 800 bar was homogenized on the M -1 10 Y microfluidizer® with potassium sulfate solution as dispersion phase at Δp = 400 bar for the following examples, unless stated otherwise. Example 3 (Preparation of barium sulfate nanoparticles (step b))

Two emulsions with aqueous dispersion phases with barium chloride and potassium sulfate were prepared as described in Examples 1 and 2 and homogenized separately. The two emulsions were mixed and stirred for two minutes by means of a propeller mixer (400 min ^-1 ), and then the crude emulsion was emulsified on the M -1 10 Y Microfluidizer.RTM .. In this high-pressure emulsification step, the pressure levels 200, 400, 600, 800 and 1000 bar.

The results of the droplet size distribution before and after the emulsification step show that the emulsifying pressure, depending on the emulsion system, has a decisive influence on the coalescence rate. Thus, the droplet size distribution of the emulsion does not change after the second emulsification step at a pressure of less than 400 bar in comparison to the emulsion after the first emulsification step within the scope of the measurement accuracy. From an emulsification pressure of 400 bar, however, coalescence and thus an increase in the size of the drops occur noticeably. For the present embodiment, a minimum pressure of Δp = 400 bar is necessary to coalesce the starting mini-emulsion droplets in the high-pressure homogenization step. While the Sauter diameter X _{1 2} after the emulsification step a) was still at about 400 nm, the average droplet size at an emulsification pressure of 400 bar or higher is about 7 μm. To achieve such a drop in magnification, it requires the coalescence of about 1500 emulsion drops.

The composition of the obtained mini-emulsions or mini-suspoemulsions were investigated by elemental analysis. For example, it was possible to exclude the possibility that at pressures below 400 bar the droplets coalesce and then be comminuted again, since the elemental analysis could only confirm the presence of barium chloride, but not that of the precipitate barium sulfate.

FIG. 1 shows the cumulative distribution Qs (x) of the droplet sizes x (in μm) before and after the homogenization (step b) and as a function of the emulsifying pressure. The value Q ₃ (x) indicates the sum distribution of the droplet sizes, ie the proportion of droplets of the corresponding size.

The triangles with the tip to the right (►) represent the sum distribution (Qs (x)) of the droplet sizes x after the first emulsification step; the dark squares (■) represent the sum distribution of the droplet sizes (Qs (x)) after the second emulsification step (step b)) at Δp = 200 bar; the bright circles (o) give the sum distribution of the droplet sizes after the second emulsification step at 400 bar again; the dark triangles with top tip (A) represent the cumulative distribution of the droplet sizes after the second emulsification step at Δp = 600 bar; the bright triangles with the tip at the bottom (V) represent the cumulative distribution of the droplet sizes after the second eumulation stage at Δp = 800 bar; the triangles with the tip left (M) represent the sum distribution of the droplet size after the second emulsification step at Δp = 1000 bar.

Example 4 (Influence of the Disperse Phase Part on Forced Coalescence in Step b))

Emulsions were prepared as described in Example 1 at pressures of .DELTA.p = 800 bar (barium chloride solution) or .DELTA.p = 400 bar (potassium sulfate solution) and then the mixture of both emulsions in the second emulsification step at .DELTA.p = 600 bar with the M - 1 10 Y Microfluidizer® as described in Example 3 again homogenized. The proportion of the disperse phase of the emulsions was varied between 20, 30 and 40 wt .-%, wherein the mass fractions of the remaining components were always kept constant.

The results for the droplet size distributions obtained show that the disperse phase fraction has a significant influence on the coalescence rate. It became clear that as the disperse phase fraction decreases, the coalescence rate is also reduced or completely suppressed. For a disperse phase content of 20 wt .-%, the Sauter diameter X _{1 2} changed after the second emulsification step only slightly (from about 290 nm to about 320 nm). With increasing proportion of disperse phase, the Sauter diameter X _{1 2 of} the emulsion increases drastically after the second emulsification step (step b), resulting in a droplet size of about 1100 nm at 30% by weight and 4550 nm for 40% by weight. % Disperse phase fraction.

The assumption of the constant droplet size distribution by coalescence with subsequent drop comminution could be refuted by EDX analyzes.

Example 5 (Influence of salt concentration on forced coalescence in step b)

The procedure was as described in Examples 1 and 2, wherein, in contrast to Examples 1 and 2, the barium chloride concentrations were each set to the following values: c (V1) = 0.05 mol / l; c (V2) = 0.25 mol / l or c (V3) = 0.50 mol / l. The molar ratio b was 5, as in Examples 3 to 4, which corresponded to potassium sulfate concentrations of c (V1) = 0.01; c (V2) = 0.05 and c (V3) = 0.10 mol / l. The emulsion with barium chloride solution was prepared according to Example 1 at Δp = 800 bar, the emulsion with potassium sulfate solution at Δp = 400 bar with the M -1 10 Y Microfluidizer®. Subsequently, according to Example 3, the mixture of the corresponding emulsions (V1, V2, V3) was formed, this stirred for 2 minutes with a propeller stirrer (400 min-1) and again on the M-110 Y Microfluidizer® at Δp = 600 bar homogenized. The droplet size distributions of the emulsions after the second emulsification step were investigated. The results showed that increasing the salt concentration has a stabilizing effect on the emulsion. The Sauter diameter of emulsions whose disperse phase had a barium chloride concentration> 0.25 mol / l is in the range of the value of an emulsion after the first emulsification step (X _{1 2} ~ 400 nm). For lower salt concentrations (eg 0.05 mol / l BaCl ₂ ), however, Sauter diameter to about 5 microns resulted. Further experiments have shown that even at a salt concentration of 0.12 mol / l barium chloride and correspondingly lower potassium sulfate (b = 5) coalescence of the drops can be produced after the second emulsification.

Also in this case, the assumption of the constant droplet size distribution could be refuted by coalescence with subsequent drop comminution by elemental analyzes (EDX analyzes).

Example 6 (Influence of the salt concentration on the particle size in step b))

The influence of the submitted salt concentration on the particle size of the precipitated barium sulfate was investigated. Emulsions with different dispersion phases (barium chloride solution and potassium sulfate solution) were prepared and homogenized as described in the example, the barium chloride concentrations of c (V1) = 0.04 mol / l; c (V2) = 0.08 mol / l and c (V3) = 0.12 mol / l and the potassium sulfate concentration corresponding to a molar ratio b of 5 were set. Subsequently, the mixture of the two corresponding emulsions in the second emulsification step at Δp = 600 bar as described in Example 2 with the M -1 10 Y Microfluidizer® emulsified. The particle size distributions of suspensions were after azeotropic distillation Des (40 ⁰ C, 25 mbar) was investigated. It was found that the introduced reactant concentration has a small influence on the particle size. Mean particle diameters (x _{1 2} values) between 10 nm and 13 nm always resulted for the investigated concentrations.

Example 7 (Preparation of Zinc Oxide Nanoparticles)

Starting mini-emulsions were prepared as described in Examples 1 and 2, using as the aqueous phase a 0.1 M solution of zinc sulfate in deionized water or 0.1 M sodium hydroxide solution. The high-pressure homogenization was carried out with a two-jet nozzle with a diameter (hole diameter) of d = 0.08 mm and an angle α of α = 30 °. The emulsification pressure in the first emulsification step (production of the starting mini-emulsions) was Δp = 600 bar.

The starting mini-emulsions thus obtained were mixed as described in Examples 1 and 2.

Starting from the mixture of the mini-emulsions described above, mini-suspoemulsions of zinc oxide nanoparticles were prepared as described in Example 3. Here, the two-jet nozzle described above was used. The high-pressure emulsion was pressed at Emulgi of Δp = 400 bar and Δp = 1000 bar carried out.

FIG. 3 shows the cumulative distribution of the drop sizes x in μm after the first and second emulsification steps. The value Qs (x) represents the sum distribution of the droplets (fraction of droplets of the corresponding size).

The dark squares (■) represent the cumulative distribution of the droplets after the first emulsification step; the bright circles (o) represent the cumulative distribution of the droplets after the second emulsification step at Δp = 400 bar, the dark triangles (A) represent the cumulative distribution of the droplets after the second emulsification step at Δp = 1000 bar.

At an emulsification pressure of 1000 bar, droplets with a mean diameter of about 6 μm are obtained.

Example 8 (comparison of different homogenizing nozzles)

Starting mini-emulsions were prepared from barium chloride solution (c = 0.1 mol / l) and potassium sulfate solution (c = 0.02 mol / l) as described in Example 2. The emulsification pressure in the first emulsification steps (step a)) was Δp = 600 bar.

Starting from the starting mini-emulsions, barium sulfate nanoparticles were prepared as described in Example 3. The emulsifying pressure in the second emulsifying step (step b)) was Δp = 1000 bar. The following homogenizing nozzles were used: standard orifice with diameter (hole diameter) d = 0.1 mm, standard orifice with diameter (hole diameter) d = 0.2 mm, twin jet with diameter (hole diameter) d = 0.08 mm and angle α = 30 °. FIG. 4 shows the sum distribution Qs (x) of the droplet sizes x in μm. The dark squares (■) show the cumulative distribution of droplet size after the first emulsification step; Circles (o) show the cumulative droplet size distribution after the second emulsification step at Δp = 1000 bar using the standard pinhole d = 0.1 mm; the dark triangles with the top tip (A) show the cumulative droplet size distribution using a standard 0.2 mm dia. the bright triangles at the bottom (V) show the cumulative distribution of the droplets using the dual-beam aperture described above. It was found that the coalescence of the droplets of the starting miniemulsion can be significantly increased when using a two-jet nozzle.

Claims

1Patentansprüche

1. A process for the preparation of nanoparticles, wherein in a first step a) at least two mini-emulsions and / or mini-suspoemulsions are generated, each containing at least one reactant in the disperse phase and at least one emulsifier, and in a second Step b) the mini-emulsions and / or mini-suspoemulsions thus produced are mixed in a high-pressure homogenizer.

2. A process for the preparation of nanoparticles according to claim 1, characterized in that the production of the mini-emulsions and / or mini-suspoemulsions in step a) takes place in a high-pressure homogenizer under an emulsification pressure in the range of 200 to 1000 bar.

3. A process for the preparation of nanoparticles according to any one of claims 1 or 2, characterized in that the mixing of the mini-emulsions and / or mini-suspoemulsions in step b) takes place in a high-pressure homogenizer.

4. A process for the preparation of nanoparticles according to any one of claims 1 to 3, characterized in that the mixing of the mini-emulsions and / or

Mini-suspoemulsions in step b) is carried out in a high-pressure homogenizer under an emulsification pressure in the range of 100 to 1000 bar.

5. A process for the preparation of nanoparticles according to any one of claims 1 to 4, characterized in that the mixing of the mini-emulsions and / or

Mini-suspoemulsions under step b) takes place in a high pressure homogenizer, wherein at least one pinhole is used as a homogenizing nozzle with a diameter in the range of 50 to 700 microns.

6. A process for the preparation of nanoparticles according to any one of claims 1 to

5, characterized in that the mixing of the mini-emulsions and / or mini-suspoemulsions under step b) takes place in a high pressure homogenizer, wherein two successively arranged pinhole are used as a homogenizing nozzle with a diameter in the range of 50 to 700 microns.

7. A process for the preparation of nanoparticles according to any one of claims 1 to

6, characterized in that the mixing of the mini-emulsions and / or mini-suspoemulsions under step b) takes place in a high-pressure homogenizer, wherein at least one two-jet nozzle with a diameter d in the range of 2

50 to 700 microns and an angle α in the range of 10 ° to 60 ° is used as Homogenisierdüse.

8. A process for the preparation of nanoparticles according to any one of claims 1 to 7, characterized in that the proportion of the disperse phase of the mini-emulsions and / or mini-suspoemulsions produced in step a) based on the total amount in the range of 5 to 50 wt .-% lies.

9. A process for the preparation of nanoparticles according to any one of claims 1 to 8, characterized in that the mini-emulsions and / or mini-suspoemulsions are W / O emulsions containing an aqueous disperse phase.

10. A process for the preparation of nanoparticles according to any one of claims 1 to 9, characterized in that the mini-emulsions and / or minisuspoemulsionen W / O emulsions containing an aqueous disperse phase, in which in each case at least a reactant is dissolved.

1 1. A process for the preparation of nanoparticles according to one of claims 1 to 10, characterized in that it is in the disperse phases of the

Reactants contained in mini-emulsions and / or minisuspoemulsions to molecular disperse dissolved salts, which are present in a molar concentration in the range of 0.01 to 0.5 mol / l, and which when mixing the mini-emulsions and / or mini -uspoemulsions in step b) react under precipitation of a solid.

12. A process for preparing nanoparticles according to any one of claims 1 to 1 1, characterized in that it is the reactants to a water-soluble salt containing cations selected from the group of alkali metal, alkaline earth metal, precious metal, silicon, tin, iron, nickel, Cobalt, zinc, titanium, zirconium, yttrium and cerium.

13. Nanoparticles, which are obtainable by a process in which in a first step a) two mini-emulsions and / or mini-suspoemulsions are produced, each containing at least one reactant in the disperse phase and at least one emulsifier, and in a second step b) the mini-emulsions and / or mini-suspoemulsions thus produced are mixed in a high-pressure homogenizer. 3

14. Nanoparticles according to claim 13, wherein the nanoparticles are particles having an average particle diameter in the range from 10 to 500 nm.

15. Nanoparticles obtained by a process according to one of claims 1 to 12.