EP1280597B1 - Verfahren zum herstellen einer monodisperse doppelemulsion - Google Patents

Verfahren zum herstellen einer monodisperse doppelemulsion Download PDF

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Publication number
EP1280597B1
EP1280597B1 EP01931824A EP01931824A EP1280597B1 EP 1280597 B1 EP1280597 B1 EP 1280597B1 EP 01931824 A EP01931824 A EP 01931824A EP 01931824 A EP01931824 A EP 01931824A EP 1280597 B1 EP1280597 B1 EP 1280597B1
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Prior art keywords
emulsion
phase
aqueous phase
surfactant
concentration
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French (fr)
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EP1280597A1 (de
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Fernando Leal Calderon
Philippe Gorria
Jérôme Bibette
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Centre National de la Recherche Scientifique CNRS
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Centre National de la Recherche Scientifique CNRS
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F29/00—Mixers with rotating receptacles
    • B01F29/80—Mixers with rotating receptacles rotating about a substantially vertical axis
    • B01F29/81—Mixers with rotating receptacles rotating about a substantially vertical axis with stationary mixing elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40—Mixing liquids with liquids; Emulsifying
    • B01F23/41—Emulsifying
    • B01F23/4105—Methods of emulsifying
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40—Mixing liquids with liquids; Emulsifying
    • B01F23/41—Emulsifying
    • B01F23/411—Emulsifying using electrical or magnetic fields, heat or vibrations
    • B01F23/4111—Emulsifying using electrical or magnetic fields, heat or vibrations using vibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40—Mixing liquids with liquids; Emulsifying
    • B01F23/43—Mixing liquids with liquids; Emulsifying using driven stirrers

Definitions

  • the invention relates to a process for the preparation of double emulsions monodisperses, of the water-in-oil-in-water type, by the implementation of a high pressure homogenizer.
  • Double emulsions of water-in-oil-in-water type in particular the encapsulation of various active substances at the level of the internal water. In well-defined conditions, it is indeed possible to cause the release of the active substances, encapsulated while controlling their release kinetics.
  • double monodisperse emulsions are particularly sought after because of their homogeneity: they allow in particular a regular and controllable release of the active ingredients.
  • a first method is that described in EP 442 831 and EP 517 987. This process involves the fractionation of a primary emulsion of departure, polydisperse, by successive creamings. It is long and tedious and not easily applicable on an industrial scale.
  • a second method is described in FR 97 It consists in subjecting a primary viscoelastic emulsion to controlled shear so that the same maximum shear is applied to the entire emulsion. This process has different advantages and in particular allows control of the size of the droplets of the emulsion monodisperse obtained.
  • the invention aims to solve this problem by providing an original process for preparing a monodisperse double emulsion by using a high pressure homogenizer.
  • the double water-type emulsion in oil in water consists of droplets (or globules) of an emulsion reverse, monodisperse, dispersed in a continuous aqueous phase (or phase outer water), the inverse emulsion being itself composed of droplets an internal aqueous phase dispersed in an oily phase.
  • the term monodisperse characterizes emulsions for which particle size distribution of dispersed phase droplets is very narrow.
  • Distribution is considered very narrow when polydispersity is less than or equal to 30%, and preferably of the order of 5 to 25%, example between 10 and 20%.
  • the polydispersity is defined as the ratio the standard deviation of the curve representing the variation of the volume occupied by the: dispersed material as a function of the diameter of the medium-diameter droplets droplets.
  • inverse emulsion is meant, in general terms, the dispersion of a aqueous phase in an oily phase.
  • direct emulsion refers to the dispersion of a oily phase in an aqueous phase.
  • the term “monodisperse inverse emulsion” refers to an emulsion water-in-oil type consisting of droplets of an aqueous phase dispersed in an oily phase, for which the distribution granulometric droplets of aqueous phase is very narrow (polydispersity less than 30%).
  • the process of the invention leads to a double monodisperse emulsion, that is to say a double emulsion in which the particle size distribution globules is also very narrow (polydispersity less than 30%).
  • This process leads to a double monodisperse emulsion consisting of globules of an oil-in-water emulsion dispersed in an aqueous phase external, globules representing not more than 50% of the total weight of the emulsion double.
  • the globules consist of droplets of an aqueous phase dispersed in an oily phase, the phase aqueous total contained in the blood cells representing not more than 50% of the weight total of all globules.
  • the process of the invention is carried out starting from an emulsion Ei, inverse, polydisperse, prepared conventionally according to any one of methods known from the state of the art.
  • the starting emulsion Ei comprises from 50 to 99% by weight of a phase aqueous, more preferably from 70 to 95%, for example 80 to 90% by weight, by relative to the total weight of the emulsion Ei.
  • the oily phase is not miscible with water. It includes one or several distinct oils, the nature of which is not critical in itself.
  • oil is meant according to the invention, any hydrophobic liquid substance or very slightly soluble in water, capable of being put into an aqueous emulsion in presence or absence of one or more suitable surfactants.
  • Such a hydrophobic and insoluble substance may be, for example, a organic polymer such as a polyorganosiloxane, a mineral oil such as hexadecane, a vegetable oil such as soybean oil or peanut oil or liquid crystals (lyotropic or thermotropic).
  • a organic polymer such as a polyorganosiloxane, a mineral oil such as hexadecane, a vegetable oil such as soybean oil or peanut oil or liquid crystals (lyotropic or thermotropic).
  • the oily phase contains an aliphatic, cyclic and / or aromatic C 3 -C 30 hydrocarbon.
  • the oily phase comprises dodecane.
  • Emulsion Ei comprises a lipophilic surfactant having a ratio lipophilic / hydrophilic (HLB value) less than 10.
  • HLB Hydrophilic-Lipophilic Balance
  • the nature of the surfactant that can be used for stabilization of the emulsion is more particularly chosen so as to be able to ensure a good stability of the emulsion.
  • Suitable surfactants mention may be made of fatty acid esters, preferably of C 8 -C 22 , of sorbitol such as span 80.
  • Another type of suitable surfactant is polyglycerol polyricinoleate.
  • Span 80 is a molecular mixture derived from sorbitol whose main constituent is sorbitan monooleate.
  • Examples of commercial polyglycerol polyricinoleate are Admul Wol 1403 (Quest), Radiamuls Poly 2253 (Fina) and Grindsted PGPR 90 (Danisco).
  • Polyglycerol polyricinoleates preferably used according to the invention are those by which n varies between 2 and 5 (and is for example 3) and m varies between 5 and 10 (and is for example 7).
  • the surfactant concentration of the oily phase of Ei varies between 60 and 99% by weight.
  • the oily phase may consist of only lipophilic surfactant.
  • step a) the polydisperse inverse emulsion, Ei, is converted into monodisperse inverse emulsion.
  • the technique used to do this is the one described in WO 97/38787.
  • a means for subjecting the entire emulsion to the same maximum shear consists of subjecting the entire emulsion to a constant shear.
  • the shear rate can be distinct, at a given time, for two points of the emulsion.
  • each part of the emulsion can thus be subjected to a rate of shear that varies over time.
  • Shear is said to be controlled when whatever the variation in time of the shear rate, this one passes by a maximum value that is the same for all parts of the emulsion, to a given moment that may differ from one place to another of the emulsion.
  • Suitable devices are described in application FR 97 00690 or in the international application WO 97/38787.
  • a suitable device is a duvet cell in which the shear is constant, the Couette cell consisting of two cylinders concentric in rotation with respect to each other.
  • a second device is a cell consisting of two parallel plates in motion oscillating relative to each other and between which one forces the polydisperse inverse emulsion.
  • Another device is a cell made up of two disks concentric in rotation relative to each other and between which circulates the polydisperse inverse emulsion.
  • the maximum value of the shear rate to which the emulsion is subjected primary depends on the frequency of rotation, oscillation frequency and / or the amplitude of oscillation of the movement of the plates, cylinders and disks of devices described above.
  • the man the trade can play on several parameters, namely the rotation frequency, the oscillation frequency and / or the oscillation amplitude of the movement of the plates, cylinders and discs of the devices described above, as well as on the size of the respective speakers of these different devices in the direction perpendicular to the direction of flow imposed by the movement of the surface.
  • the maximum shear rate varies linearly with oscillation amplitude and / or the frequency of movement and so inversely proportional to the size of the enclosure in one direction perpendicular to the flow.
  • the maximum shear rate be between 1 and 1.10 5 s -1 , preferably between 100 and 5000 s -1 , for example between 500 and 5000 s -1 .
  • a homogeneous flow is characterized by a constant velocity gradient in a direction perpendicular to the moving solid surface.
  • One way to control the flow is to play on the dimension of speakers in the direction perpendicular to the flow direction imposed by the movement of the surface.
  • this dimension d is defined by the difference (R 3 -R 2 ) in which R 2 and R 3 are respectively the radii of the inner and outer cylinders of the Couette device.
  • this dimension d is defined by the distance separating the two plates in a direction that is perpendicular.
  • this dimension is defined by the distance separating the two disks in the direction of the axis of rotation of the disk in movement.
  • a heterogeneous flow can be made uniform by reducing the size of the enclosure and more particularly by reducing its dimension in the direction perpendicular to the direction of flow.
  • the d is preferably maintained below 200 ⁇ m, for example between 50 and 200 microns, in particular about 100 microns.
  • an inverse emulsion of which the size of the dispersed aqueous phase droplets is between 0.05 ⁇ m and 50 ⁇ m, preferably between 0.1 ⁇ m and 10 ⁇ m.
  • step b) the monodisperse inverse emulsion obtained in step a) is diluted by addition of an oily dilution phase.
  • the exact nature of the oily dilution phase is however not crucial according to the invention.
  • oily dilution phase is as defined above for the oily phase of the emulsion Ei.
  • the addition of the oily dilution phase is carried out conventionally without phase inversion.
  • a simple method consists in adding dropwise said oily addition phase to the monodisperse inverse emulsion maintained with moderate stirring. For this purpose shearing less than 100 s -1 is generally appropriate.
  • shearing less than 100 s -1 is generally appropriate.
  • other methods of addition such as, for example, the one-time addition of the oily dilution phase, to the emulsion kept stirring.
  • the mass fraction of aqueous phase (ratio of the weight of the aqueous phase to the total weight of the emulsion) is less than 0.5, preferably less than 0.35, more preferably less than 0.20.
  • the viscosity of the inverse emulsion is less than 0.1 Pa.s, preferably less than 0.01 Pa.s.
  • step c) the emulsion resulting from step b), which is a Monodisperse inverse emulsion, in a high pressure homogenizer.
  • the high pressure homogenizer that can be used according to the invention is of the type commonly used for the preparation of stable emulsions from a aqueous phase and an oily phase.
  • Such homogenizers include as described by W. Clayton in The Theory of emulsions and Their technical treatment, 5 th edition, Churchill Livingstone, London, 1954; or by LW Phipps in The High Pressure Dairy Homogenizer, The National Institute for Research in Dairying, 1985; or by H. Mulder and P. Walstra in The Milky Fat Globule, Center for Agricultural Publishing and Documentation, Wegeningen, The Netherlands, 1974; or by P. Walstra in Formation of emulsions, Encydopedia of emulsion technology, Paul Becher, vol. 1, p. 57-127, Marcel Dekker Ed., New York, 1983.
  • the liquids are forced to very high pressure (a few hundred bars, for example 100 to 400 bars) to go to through a very narrow aperture of millimeter or micrometer size.
  • This opening is usually placed in a valve system but it may be a slot or a simple circular hole. The opening usually presents a diameter of between 10 ⁇ m and 1 mm. Passing through this opening narrow, the emulsion undergoes a violent acceleration as well as a sudden fall pressure (the pressure downstream of the opening is of the order of 1 bar). Forces cavitation, shear and resulting turbulence emulsification.
  • Said continuous aqueous phase will constitute the aqueous phase outer of the double emulsion exiting the high pressure homogenizer. He must It is to be understood that the continuous aqueous phase is an aqueous solution.
  • a suitable homogenizer is a homogenizer of Gaulin type such as the model marketed by LabPlant Limited. In a way preferred, this model does not require premixing of the phases.
  • the emulsion obtained at the end of step b) and the aqueous phase are initially contained in two separate cylindrical tanks surmounted by two pistons, located downstream of a homogenization chamber. Pushing on pistons, a press forces both liquids to penetrate simultaneously into the homogenisation chamber before passing them through the circular orifice Release.
  • the continuous aqueous phase used in step c) does not include thickener. It may contain one or more surfactants hydrophilic.
  • the final emulsion is produced after a single pass through the high pressure homogenizer.
  • a second pass may cause a decrease considerable number of internal droplets contained in the globules (by coalescence). This would result in premature leakage of the active ingredient into the external aqueous phase.
  • the hydrophilic surfactant concentration of the continuous aqueous phase of step c) is less than 0.02 times the critical micelle concentration; of preferably, it is less than 0.01 times the critical micelle concentration.
  • CMC Critical Micellar Concentration
  • the concentration of hydrophilic surfactant the continuous aqueous phase may be zero.
  • a surfactant added to the double monodisperse emulsion coming out of the high-pressure homogenizer, as a stabilizer, a surfactant additional and, advantageously, as soon as possible at the exit of the high pressure homogenizer.
  • the additional surfactant that can be used as an emulsion stabilizer double monodisperse is of the same type as that possibly present in the aqueous dilution phase; it is a hydrophilic surfactant.
  • This additional surfactant may be nonionic, ionic, zwitterionic or amphoteric.
  • the hydrophilic surfactant of the aqueous dilution phase of step c) advantageously has a lipophilic-hydrophilic ratio (HLB value) greater than 20, preferably greater than 30.
  • the HLB value is about 40.
  • the additional surfactant meanwhile has preferably a value HLB greater than 12.
  • Such polymers are marketed by ICI under the brand name Synperonic PE®.
  • the kinematic viscosity of the polymers of Synperonic PE® type is preferably between 150 and 1200 mm 2 .s -1 at 100 ° C., more preferably between 500 and 1100 mm 2 .s -1 .
  • the surfactant present in the continuous aqueous phase of step c) is selected from a fatty acid ester of sorbitol; the condensation product of a fatty acid ester of sorbitol with a alkylene oxide; an alkyl sulphate or an ethoxylated and / or propoxylated derivative of this one ; a quaternary ammonium salt; and their mixtures.
  • the additional hydrophilic surfactant added to the final double emulsion leaving the homogenizer is chosen from an ester fatty acid sorbitol; the condensation product of a fatty acid ester of sorbitol with an alkylene oxide; a water-soluble block copolymer ethylene oxide and propylene oxide; and their mixtures.
  • the concentration of additional surfactant is to be adjusted by the man of art to ensure the encapsulation of the active ingredient and prevent breakage of the emulsion.
  • the concentration of said surfactant will preferably be less than 1 time his CMC. If the HLB of the hydrophilic surfactant is less than 20, then the concentration of said surfactant will preferably be less than 100 times its CMC.
  • the aqueous phase of the starting emulsion Ei comprises at least one substance active water-soluble.
  • Such active substances are preferably in the form of salts or of water-soluble polymers.
  • vitamins (E, C) can thus be chosen from vitamins (E, C), enzymes, insulin, analgesic, antimitotic, anti-inflammatory or antiglaucomatous agents, vaccines, anti-cancer agents, narcotic antagonists, detoxification agents (salicylates, barbiturates), depilatory agents, corrective agents or masks taste, water soluble salts, acids, bases, vinegar, glucose, dyes, preservatives or their mixtures.
  • a salt such as an alkali metal chloride (NaCl or KCl) or a water-soluble polymer such as alginate, hydroxyethylcellulose, carboxymethylcellulose or a poly (acrylic acid) or a carbohydrate monosaccharide such as fructose, lyxose, arabinose, ribose, xylose, glucose, altrose, mannose, idose, galactose, erythrosis, threose, sorbose, fucose or rhamnose, glucose being clearly preferred.
  • a salt such as an alkali metal chloride (NaCl or KCl) or a water-soluble polymer such as alginate, hydroxyethylcellulose, carboxymethylcellulose or a poly (acrylic acid) or a carbohydrate monosaccharide such as fructose, lyxose, arabinose, ribose, xylose, glucose, altrose, man
  • the concentration of active substance depends on the nature of the substance active and the intended application.
  • the continuous aqueous phase of step c) comprises one or several osmotic pressure balancing agents.
  • balancing agents that can be used according to the invention, the man of the profession may implement any of the balancing agents commonly used in the art.
  • Particularly preferred examples are sorbitol, glycerol and mineral salts such as ammonium salts and alkali metal salts or alkaline earth metal.
  • a carbohydrate is used monosaccharide, such as fructose, lyxose, arabinose, ribose, xylose, glucose, altrose, mannose, idose, galactose, erythrosis, threose, sorbose, fucose or rhamnose, glucose being clearly preferred.
  • the balancing agent concentration will be determined in order to ensure the osmotic balance between the internal aqueous phase of the final double emulsion and the external continuous aqueous phase of the emulsion double. It depends on the osmolality of the hydrophilic active substance (s) (present in the internal aqueous phase) as well as the osmolality of said agent balancing in the continuous aqueous phase.
  • the process of the invention makes it possible to prepare double emulsions the size of the globules varies between 1 and 50 ⁇ m, especially in the range 2 and 20 ⁇ m, more preferably between 2 and 10 ⁇ m.
  • the droplet diameter value of the emulsion Ei can be measured by implementing any of the known methods of the prior art two of these methods are commonly used in the art.
  • the first is phase contrast microscopy
  • the second is laser particle size.
  • a third suitable method for the case of emulsions consisting of at least 65% by weight of dispersed phase is to fill the double emulsion cell allowing the transmission of at least 80% of the incident light.
  • the concentration of surfactant present in the continuous aqueous phase of step c) determines the size of the globules in the final double emulsion.
  • Another way to control the size of the globules of the double emulsion final step is the control of the total amount of lipophilic surfactant present in the oily phase of the monodisperse inverse emulsion prepared in step b). This amount does not exactly correspond to the sum of the surfactant lipophilic initially present in the inverse emulsion Ei and lipophilic surfactant optionally present in the oily dilution phase added in step b), but he is inferior.
  • a part of the surfactant is adsorbed at the oil-water interface, that is to say on the surface of the droplets of aqueous phase.
  • the amount of surfactant remaining in the oily phase of the inverse emulsion amount that does not take into account the surfactant adsorbed at the water-oil interface.
  • this sequence is repeated at least twice.
  • concentration real in surfactant of the oily phase allows a perfect control of the size globules of the final double emulsion.
  • the method of the invention finds applications in many areas such as pharmaceuticals, cosmetics, the field of detergents, the field of liquid crystal display, the field of phytosanitary and water-based paints.
  • the emulsions of the invention are also useful in the treatment of surfaces.
  • the device used for the preparation of emulsions monodisperse inverses from corresponding polydisperse emulsions is the Couette cell shown in Figure 1: this consists of two concentric cylinders 2 and 3 in constant rotation relative to each other.
  • the inner cylinder 2 is stationary whereas the outer cylinder 3 is with a uniform rotational movement with respect to a drive axis 15.
  • the concentric cylinders 2 and 3 define an annular enclosure 4.
  • To the upper and lower ends of the enclosure 4 are arranged two bearings sealed ball bearings 5 and 6 annular.
  • a cover 7 whose dimensions correspond to those of the outer cylinder 3 closes the upper part of the device 1.
  • the cylinders 2 and 3 concentric are offset relative to each other in the direction of the length so that the lower part 8 of the cylinder internal rests on a plane support 9.
  • the quilt cell 1 shown in FIG. a supply duct 10 in polydisperse emulsion which passes through the support 9 and opens into the upper part 11 of the enclosure 4.
  • the other end of the feed duct is connected to a reservoir 12 containing the emulsion polydisperse.
  • the polydisperse emulsion feed rate is controlled by a piston 13.
  • the lower part of the chamber 4 diametrically opposite the point 11 is provided with a discharge line 14 of the monodisperse emulsion which passes through the flat support 9.
  • the device of FIG. 1 allows the continuous preparation of the emulsion monodisperse target.
  • enclosure 4 is powered by continuous emulsion polydisperse by the pipe 10.
  • the polydisperse emulsion circulates in the chamber 4 while being subjected to shear forces generated by the uniform rotation of the outer cylinder 3 on itself.
  • the polydisperse emulsion is subjected to a constant shear rate, the shear rate being defined here as the ratio of the linear velocity to the point of contact with the surface of the outer cylinder 3 to the difference (R 3 -R 2 ) where R 2 and R 3 are respectively the radii of the inner and outer cylinders 2 and 3.
  • the size of emulsion droplets E i was determined in all cases by phase contrast microscopy and by laser granulometry.
  • a polydisperse inverse emulsion is prepared, in sorbitan monooleate (SPAN 80), this constituent plays both the role of oil and surfactant.
  • This inverse emulsion is prepared in introducing a 0.4M aqueous solution of sodium chloride in one continuous, kept under constant agitation and consisting of monooleate sorbitan. The amount of aqueous solution added is such that the phase dispersed aqueous represents 85% of the total mass of the emulsion.
  • This inverse emulsion is then sheared at a shear rate of 1890 s -1 in a Couette device characterized by a gap of 100 .mu.m.
  • the inverse emulsion obtained Ei ° is monodisperse, the average diameter of the droplets of internal aqueous phase being 0.35 .mu.m.
  • the inverse emulsion Ei ° is then diluted in the dodecane, so as to that the dispersed aqueous phase represents about 20% of the total mass emulsion.
  • This dilution operation consists in gradually adding the dodecane with the inverse emulsion Ei °, while maintaining a weak agitation and constant.
  • the inverse emulsion obtained is "washed" so as to know the concentration of lipophilic surfactant in the oily continuous phase.
  • the high pressure homogenizer comprises 2 tanks for the introduction of a continuous aqueous phase on the one hand, and of the inverse emulsion diluted on the other go.
  • the previous inverse emulsion is introduced into one of the tanks and the aqueous continuous phase of the final double emulsion (continuous aqueous phase) in the other.
  • the continuous aqueous phase consists of water, 10.5% weight of glucose (this amount of glucose has been chosen to balance the osmotic pressures with the aqueous dispersed phase of the inverse emulsion, consisting of 0.4M salt) and 0.005 times sodium dodecyl sulfate critical micellar concentration. Both fluids are then emulsified in the mixing chamber of the homogenizer at a pressure of about 300 bar.
  • the diameter of the outlet orifice chosen is 0.62 mm.
  • FIG. 3 represents the particle size distribution of the emulsion double final.
  • the inverse emulsion is washed by operating as in Example 1 with a continuous phase consisting of dodecane and sorbitan monooleate with 1% and 2% by weight. We thus obtain two inverse emulsions with two sorbitan monooleate concentrations in the oily continuous phase.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Colloid Chemistry (AREA)
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Claims (20)

  1. Verfahren zur Herstellung einer monodispersen Doppelemulsion vom Typ Wasser-in-Öl-in-Wasser, dadurch gekennzeichnet, daß es die folgenden Stufen umfaßt:
    a) Unterwerfen einer polydispersen Emulsion Ei des Typs Wasser-in-Öl, die 50 bis 99 Gew.-% einer wäßrigen Phase umfaßt, einer gesteuerten Scherbehandlung in der Weise, daß die gleiche maximale Scherwirkung auf die Gesamtheit der Emulsion einwirkt, zur Bildung einer entsprechenden monodispersen inversen Emulsion;
    b) Zugeben der notwendigen Menge einer öligen Verdünnungs-Phase zu der genannten Emulsion ohne Phasenumkehr, in der Weise, daß die wäßrige Phase der gebildeten Emulsion mindestens 50 Gew.-% des Gesamtgewichts der Emulsion repräsentiert; und
    c) Einführen der gebildeten Emulsion zusammen mit einer kontinuierlichen wäßrigen Phase in eine Hochdruck-Homogenisiereinrichtung, wobei die Mengen der Emulsion und der kontinuierlichen wäßrigen Phase derart sind. daß die gebildete Doppelemulsion bis zu 50 Gew.-% Tröpfchen der inversen Emulsion enthält, bezogen auf das Gesamtgewicht der Emulsion, und die wäßrige kontinuierliche Phase eine Konzentration an hydrophilem oberflächenaktivem Mittel aufweist, die kleiner oder gleich ist dem 0,02-fachen der kritischen Mizellenkonzentration.
  2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die gesteuerte Scherbehandlung in der Weise durchgeführt wird, daß man die genannte polydisperse Emulsion Ei mit einer festen bewegten Oberfläche in Kontakt bringt, wobei der das Fließen der Emulsion kennzeichnende Geschwindigkeitsgradient in einer Richtung senkrecht zu der bewegten festen Oberfläche konstant ist.
  3. Verfahren nach einem der Ansprüche 1 und 2, dadurch gekennzeichnet. daß die Scherbehandlung mit Hilfe einer Zelle durchgeführt wird, die aus zwei konzentrischen Zylindern gebildet ist, die in bezug zueinander rotieren.
  4. Verfahren nach einem der Ansprüche 1 und 2, dadurch gekennzeichnet. daß die Scherbehandlung mit Hilfe einer Zelle bewirkt wird, die aus zwei parallelen Platten gebildet ist, die sich in bezug zueinander oszillierend bewegen.
  5. Verfahren nach einem der Ansprüche 1 und 2, dadurch gekennzeichnet, daß die Scherbehandlung mit Hilfe einer Zelle bewirkt wird, die aus zwei konzentrischen Scheiben gebildet ist, die in bezug zueinander rotieren.
  6. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß der Maximalwert des Schergrads 1 bis 1·105 s-1, vorzugsweise 100 bis 5000 s-1 beträgt.
  7. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die Emulsion Ei 70 bis 95 Gew.-% der wäßrigen Phase, vorzugsweise 80 bis 90 Gew.-%, umfaßt.
  8. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß in der Stufe b) die zugesetzte Menge der öligen Phase derart ist, daß die wäßrige Phase der gebildeten Emulsion 35 Gew.-% oder weniger des Gesamtgewichts der Emulsion ausmacht, vorzugsweise 20 Gew.-% oder weniger.
  9. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß in der Stufe c) die Viskosität der in die Hochdruck-Homogenisiereinrichtung eingeführten Emulsion einerseits und die Viskosität der kontinuierlichen wäßrigen Phase andererseits weniger als 0,1 Pa.s, vorzugsweise weniger als 0.01 Pa.s betragen.
  10. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß das in der kontinuierlichen wäßrigen Phase der Stufe c) vorhandene oberflächenaktive Mittel ein Lipophil-Hydrophil-Verhältnis (HLB-Wert) von mehr als 20, vorzugsweise mehr als 30 aufweist.
  11. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die kontinuierliche wäßrige Phase der Stufe c) als oberflächenaktives Mittel einen Sorbitol-Fettsäureester; das Kondensationsprodukt aus einem Sorbitol-Fettsäureester mit einem Alkylenoxid; ein Alkylsulfat oder ein ethoxyliertes und/oder prapoxyliertes Derivat davon; ein quaternäres Ammoniumsalz; oder Mischungen davon umfaßt.
  12. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die Konzentration des oberflächenaktiven Mittels der kontinuierlichen wäßrigen Phase der Stufe c) weniger als das 0,01-fache der kritischen Mizellenkonzentration beträgt.
  13. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die wäßrige Phase der Emulsion Ei eine aktive Substanz umfaßt und die kontinuierliche wäßrige Phase der Stufe c) ein Mittel zum Ausgleich des osmotischen Drucks umfaßt.
  14. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß man der in der Stufe c) gebildeten monodispersen Doppelemulsion ein zusätzliches oberflächenaktives Mittel als Stabilisator zusetzt.
  15. Verfahren nach Anspruch 14, dadurch gekennzeichnet, daß das oberflächenaktive Mittel ein Lipophil-Hydrophil-Verhältnis (HLB-Weirt) von mehr als 12 aufweist.
  16. Verfahren nach einem der Ansprüche 14 und 15, dadurch gekennzeichnet, daß das oberflächenaktive Mittel ausgewählt ist aus einem Sorbitol-Fettsäureester; dem Kondensationsprodukt aus einem Sorbitol-Fettsäureester mit einem Alkylenoxid; einem wasserlöslichen Sequenzcopolymeren aus Ethylenoxid und Propylenoxid; und Mischungen davon.
  17. Verfahren nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß man zur Variation der Größe der Tröpfchen der inversen Emulsion in der endgültigen Doppelemulsion die Konzentration des hydrophilen oberflächenaktiven Mittels in der kontinuierlichen wäßrigen Phase der Stufe c) einstellt.
  18. Verfahren nach einem der Ansprüche 1 bis 16, dadurch gekennzeichnet. daß man zur Variation der Größe der Tröpfchen der inversen Emulsion in der endgültig erhaltenen Doppelemulsion die reelle Konzentration des lipophilen oberflächenaktiven Mittels einstellt, welches in der öligen Phase der monodispersen inversen Emulsion enthalten ist, die am Ausgang der Stufe b) erhalten wird.
  19. Verfahren nach Anspruch 18. dadurch gekennzeichnet, daß man die reelle Konzentration des lipophilen oberflächenaktiven Mittels dadurch einstellt, daß man nach der Stufe b) und vor der Stufe c) eine Behandlungssequenz durchführt. die durch die folgenden Stufen gebildet ist:
    i) Zentrifugieren der am Ausgang der Stufe b) erhaltenen inversen Emulsion ohne ein Zusammenfließen der Tröpfchen der wäßrigen Phase zu bewirken, bis zur Dekantierung der Phasen:
    ii) Abtrennen der öligen Phase in an sich bekannter Weise;
    iii) Zugeben einer öligen Ersatzphase mit einer vorbestimmten Konzentration an lipophilem oberflächenaktivem Mittel zu der verbleibenden Phase, welche aus den sedimentierten und durch das lipophile oberflächenaktive Mittel stabilisierten Tröpfchen der wäßrigen Phasen gebildet ist;
    iv) Redispergieren der Emulsion unter geeigneter Scherwirkung und unter Vermeidung einer weiteren Fragmentierung der Tröpfchen der wäßrigen Phase.
  20. Verfahren nach Anspruch 19, dadurch gekennzeichnet, daß die am Ausgang der Stufe b) erhaltene inverse Emulsion mindestens zweimal und in dieser Reihenfolge der genannten Behandlungssequenz aus den Stufen i) bis iv) unterworfen wird, und zwar vor der Durchführung der Stufe c).
EP01931824A 2000-05-09 2001-05-09 Verfahren zum herstellen einer monodisperse doppelemulsion Expired - Lifetime EP1280597B1 (de)

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FR0005880 2000-05-09
FR0005880A FR2808703B1 (fr) 2000-05-09 2000-05-09 Procede de preparation d'une emulsion double monodisperse
PCT/FR2001/001397 WO2001085319A1 (fr) 2000-05-09 2001-05-09 Procede de preparation d'une emulsion double monodisperse

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US20090211492A1 (en) * 2005-12-10 2009-08-27 Hawes Charles L Composition for thinning of oil-based paint
FR2897362B1 (fr) * 2006-02-13 2008-04-18 Inst Francais Du Petrole Methode de traitement des puits par emulsions de petite taille contenant des additifs
JP5200425B2 (ja) * 2006-06-23 2013-06-05 住友化学株式会社 農薬活性微生物製剤
EP2489427A1 (de) * 2011-02-16 2012-08-22 Helmholtz-Zentrum für Infektionsforschung GmbH Vorrichtung und Verfahren zur Herstellung und Analyse von Prionen
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US20040116541A1 (en) 2004-06-17
AU5851701A (en) 2001-11-20
WO2001085319A1 (fr) 2001-11-15
ATE281881T1 (de) 2004-11-15
EP1280597A1 (de) 2003-02-05
WO2001085319A9 (fr) 2008-10-02
CA2408419C (fr) 2009-07-21
DE60107073D1 (de) 2004-12-16
CA2408419A1 (fr) 2001-11-15
FR2808703B1 (fr) 2002-08-02
ES2227188T3 (es) 2005-04-01
AU2001258517B2 (en) 2005-09-08

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