CN102879317A - Accelerated stability assessment of dispersions and emulsions - Google Patents

Abstract

The invention provides accelerated stability assessment of dispersions and emulsions. A method and apparatus for determining the stability of dispersions and emulsions (100, 10N) accelerates the onset of significant particle agglomeration in a sample by stressing the sample by reducing the height of the interparticle potential energy barrier between the particles. This is achieved by adding one or more of three stress factors (111, 11N); changing the pH of the sample to reduce the surface charge on the particles; adding an adsorbing electrolyte so that ions of the appropriate charge are adsorbed onto the surfaces of the particles to reduce the net charge on the particles; and applying a monovalent, divalent, or trivalent salt to partially screen electrostatic repulsions between the charged particles. In a preferred embodiment, the increase in agglomeration is detected with single particle detection, such as SPOS, to generate a PSD (12) from which a figure of merit (16) is derived. Another embodiment detects turbidity or light scattering to generate a value X indicative of the extent of agglomeration.

Description

The accelerated stability assessment of disperse phase and emulsion

The application is applicant Stable Solutions Inc., the applying date to be the dividing an application of Chinese patent application No.200480023803.3 of the same name on June 14th, 2004.

Technical field

The present invention relates to a kind of method and apparatus of system, be used for by disperse phase and emulsion stress application are come the beginning of accelerated particle agglomeration or droplet coalescence, and assess thus their stability, and estimate their quality and performance.

Background technology

It is to depend on dispersion or be suspended in the fine particle that in the liquid (being generally water), therefore is classified as binary system that many products and middle rapidoprint are arranged in broad commercial applications.These particles can be solids, for example in the situation that liquid polymer suspending liquid.Alternatively, " particle " can be included in the drop that can not normally dissolve each other in the suspending liquid-for example oil droplet in the oil-in-water emulsion situation, the perhaps water droplet in the water-in-oil type emulsion situation (usually containing water-soluble substances).Simultaneously, more complicated disperse phase exists with multiphase system, forms for example W/O/W type and Water-In-Oil oil-in emulsion.

The particle or the drop that comprise " disperse phase " have sizes usually, and its scope is usually from 0.1 micron (micron, or μ m) or be smaller to 1 μ m or larger.The particle of specific products or the distribution of drop size depend on the chemical composition (comprising the spreading agent that is combined with particle or drop) of disperse phase or the emulsion of discussion and are used for obtaining the physical mechanism of final products.The latter's example is included in the homogeneization in the oil-in-water emulsion situation, and the emulsion polymerization in the polymer suspension situation.No matter disperse phase forms by solids or by drop, and what claim easily particle or drop size is distributed as " particle " Size Distribution, perhaps PSD, the usage of inferring or meaning to be without loss of generality by PSD.Word used herein " particle " is intended to both comprise and also comprises drop by solids.Similarly, also easily product is referred to as by " disperse phase ", infers or mean to be without loss of generality by it.Therefore, word used herein " disperse phase " refers to both comprise that emulsion also comprises suspending liquid.

The example that many widely used products based on disperse phase, suspending liquid or emulsion are arranged.The representative as its far-ranging existing application is wanted in following tabulation, but it is whole anything but:

A) inorganic (for example silica, aluminium oxide and cerium oxide) soliquid, the chemical-mechanical planarization (CMP) that is used for silicon wafer in fabrication of semiconductor device is processed;

B) liquid polymer suspending liquid is used for paint, coating, bonding agent and sealant;

C) edible oil-in-water emulsion (comprising fragrance and color) is used for drink and food, for example soy sauce, flavouring and food additive;

D) based on the emulsion of silicones, be used for wash my hair (shampoo) and humidification, profit hand emulsion and operation washing, and sealant, flexible perfusion compound and medical implant;

E) aqueous emulsion of the content of wax and/or clay is used for the cosmetics preparation;

F) based on the oil-in-water emulsion of soybean, safflower, olive, median chain triglyceride oil and/or fish oil, be used for intravenously administrable (for example anesthesia) and parenteral alimentation and supply with;

G) based on the suspending liquid of pigment, be used for conventional printing with ink jet type;

H) based on the oil-in-water emulsion of silane, be used for applying of water-proofing agent;

I) inorganic (for example titanium dioxide) soliquid is used for dyeing and opacifier;

J) homogeneous whole milk (or degreasing) disperse phase;

K) water-in-oil type emulsion and microemulsion are used for lubricant and fuel;

L) oil-in-water emulsion is used for ultrasound contrast imaging (ultrasound constrast imaging);

M) based on the oil-in-water emulsion of pitch, be used for highway maintenance.

These and other all extremely depends on their stability between idle and operating period based on the effect of the product of disperse phase or emulsion.In the context of the present invention, term " stability " refers to the particle that comprises disperse phase and keeps separating through time cycle of an elongated segment (ideally, being indefinite duration), and can not produce obvious agglomeration or coalescent tendency.The stability of given disperse phase or emulsion typically is not only the function of its chemical composition, but also is the function of " details " of its related production run.These " quality " or performances based on the final products of disperse phase or emulsion and middle rapidoprint are usually relevant with their stability, that is, to trend towards unsettled potential relevant with ordering about them.The performance of these products is usually closely related with the PSD of the disperse phase of discussing or emulsion.Be subjected to the example of the important physical that PSD affects to comprise viscosity, hardness, intensity, conduction (heat and electricity), outward appearance, color, tone, gloss, mouthfeel and quality.

Physical and chemical stability is the important results of using any commercial available suspending liquid or disperse phase.Unstable disperse phase is characterised in that, inversion can occur the space distribution of disperse phase, otherwise is that agglomeration or coalescent irreversibly occurs respectively for equally distributed fine particle or drop.In the situation that liquid dispersed phase (such as oil-in-water type or water-in-oil type emulsion), droplet coalescence produces larger, excessive " globule " of size, finally causes the phase separation on the macro-size.The process of this particle aggregation effect or droplet coalescence not only causes the increase of averaged particles/drop size, but also causes the increase of " polydispersity " or particle/drop size range, comprises total PSD.Agglomeration or the coalescent destructive effect of tool usually occur in its logarithm approximately than large 1/2 to 1 the range of size of logarithm of averaged particles or drop size in the disperse phase of commodity production or the emulsion.This range of size that obviously changes is called as the major diameter " afterbody " (large-diameter " tail ") of PSD, and usually is most interested in.Consist of the quantity of the colony relatively far away of stable dispersion phase PSD afterbody, no matter be based on quantity or volume weighting, usually all account for less than 1% of (usually far less than) total dispersion phase.Compare with " benchmark " value that derives from " good " (stable, high-quality) product, the growth of PSD afterbody can occur in any stage---namely, in production, storage or production marketing process, perhaps in subsequently industry or private consumption person's separator or suboptimum use procedure.

The failure may occur in every way: so that the product of final production is not attractive, can not with or even in consumer's hand, be dangerous.Such failure has a large amount of common examples, comprising: the taste bad will relevant with unsettled beverage concentration, dairy produce, food seasoning or flavoring; The appearance poor or the ink plug nozzle that are caused by large particle aggregation effect; During by the CMP slurry polishing, form flaw (for example, cut) on the surface of silicon wafer, cause the production declining of semiconductor devices; Respectively since the flocculation that latex particle or wax emulsion drip cause by multicomponent paint or protectiveness finish paint coating surface the time not good enough or or not basic; The injury that the human or animal is caused because the nutrient that vein is introduced or medicine contain the liposome of excessive coalescent oil droplet or agglomeration/fusion.

The financial cost that the disperse phase of industrial level or these and other of emulsion are failed can be sizable, the intermediate materials that especially produces with the suboptimum Product Process or those relevant costs of the internal losses of final products.Owing to lack understanding or be difficult to the variation monitoring and control, these losses can occur in New Product Development Process, perhaps occur in the production run with approved product (established product) that (batch-to-batch) changes between wider batch.When inferior product has been escaped the detection rules before the list marketing and must have been recalled in a large number subsequently, even can cause higher loss.In addition, the industrial consumer is with the extensive use as the starting material of final commercial product or essential composition of disperse phase or emulsion, and is inevitable with the potential risk than the large economy loss.Finally, as fruit product be intended in the human body using or contain extremely volatilization or combustible component, so subsequently unfavorable or or even fatal result's meeting so that unsuccessfully relevant health and economic risk is more serious with product.

In many cases, interested product or material are colloid in essence, wherein most particles (or drop) are less than 1 μ m, the population mean diameter is typically at 0.05-0.10 μ m(" microemulsion "), 0.10-1.0 μ m(" little emulsion ") or 1.0-10.0 μ m(" large emulsion ") in the scope.Suppose that measurement technology has enough sensitivity and resolution, the determining of PSD provides the valuable of the stability of these disperse phase and emulsion and quality and usually has been unique " window ".Such information has epochmaking potential value, because the perturbation that it can be the effect of judging given production run and the latter provides quantitatively, objective criterion.Finally, this knowledge can be informed the device for the production run of product that production optimization is discussed.

As from obviously finding out the above-mentioned listed application, the type that disperse phase and emulsion the most extensively run into is the aqueous solution system, and " continuously " phase (continuous phase) of wherein surrounding the disperse phase of particle or drop is comprised of water.(water is not water purely.It always comprises electrically charged and uncharged molecule that one or more electrically charged, movable particles (electrolyte) add that other may dissolve, together with the H of the required any concentration of the pH that sets up dispersion medium ⁺And OH ^-Ion.) therefore, being used for the physical mechanism that stabilize water disperse phase and emulsion institute the most extensively adopts is that charge stable is machine-processed.First of this mechanism is extensively described the classical monograph at them by Verwey and Overbeek: Theory of Stability of Lyophobic Colloids, ElsevierScience, Amsterdam(1984) in provide.Replenishing of this theory provided by Derayaguin and Landau, and " dlvo theory " of the colloidal stability that forms (because Derayaguin, Landau, Verwey and Overbeek) verify by many authors, comprise that Hiemenz exists: Principles of Colloid and Surface Chemistry (colloid and surface chemistry principle), Marcel Dekker, New York(1997) and middle checking.This theory provides the quantitative description of competing between two kinds of being present between the adjacent particles that is suspended in aqueous medium power basic, that effect is opposite-coulomb (static) repulsive force and the London-Van der Waals force.

Interparticle electrostatic repulsion forces from particle surface with net charge (positive charge or negative charge).This electric charge can be by producing---that is, they are intrinsic parts of the particle of discussing---with the part of surperficial covalent bonding and by ionic dissociation is lost the neutrality of described particle to aqueous phase on every side." counterion " of these oppositely chargeds is released in the external phase, therefore stays from the teeth outwards the degree of net charge, depends on the value of single dissociation constant, and perhaps the surface bond part is with respect to " titratable " pKa of the pH of water on every side.A kind of example is the Carboxylated Polystyrene latex particle---namely, contain the latex " pearl " of COOH base of surperficial covalent bonding with them.If the pH value of water is much larger than the pKa(of COOH base namely, 2 pH units on the 〉=pKa value), most H ⁺Ion will from the latter from solution, stay the electronegative COO that invests particle surface ^-Base.On the contrary, when reaching the pKa value, the pH of water (that is, in the time of pH=pKa), only has 50% H ⁺Ionic dissociation.The worst situation is, if pH is lower than the pKa value, surface charge greatly reduces, even reaches zero, and this is because more H ⁺Ionic adsorption is on particle, and disperse phase becomes unstable.

Alternative scheme is to remain in and guarantee on the particle that their stable net charges can provide by being adsorbed in their lip-deep charged molecules.Be that polystyrene latex particle (not with the COOH group) provides common example equally, but in this example, surrounded by the molecule of ionic surfactant, such as sodium dodecylsulphonate (SDS).The hydrophobic hydrocarbon of SDS monomer " afterbody " is adsorbed on the surface of same hydrophobic polymer particle and/or inner, and hydrophilic head group is successfully arranged and is present on the surface, to allow being exposed to the most possibly ambient water molecule.Most of Na ⁺Ion freely is diffused in aqueous phase, the SO of the SDS monomer by belonging to absorption ₃The strength of-group is stayed net negative charge on the surface of particle.

As the result who remaines in the net charge on the given particle surface, there is in its surface electromotive force Ψ ₀, null value is defined as apart from particle infinitely great.The distance of distance particle surface be the potential value Ψ (x) at x place with the increase of x monotone decreasing, show such as the diagram among Fig. 1.Distance parameter x be standardized interparticle distance from, be defined as x=(r-2a)/2a, wherein r is the distance between two particle (the being assumed to sphere) center, and a is the radius (supposition particle measure-alike) of each particle.Closely around the zone of each particle surface, be commonly referred to " stern layer (Stern Layer) ", contain the ion that has with the relatively high concentration of particle surface electric charge opposite in sign, and be adsorbed onto each particle surface.The concentration of the ion of these opposite charge is along with progressively descending with the increase of particle surface spacing.On the contrary, with the concentration of the charged ion identical than the entrained electric charge symbol of macroparticle along with increasing with the increase of each particle surface distance.Contain can be between macroparticle the positively charged and electronegative removable ion of the free diffusing diffusion region that exceeds stern layer be called as the Gouy-Chapman layer.Suppose the description according to the Coulomb law, have common 1/x performance for monopole, the Ψ that then shows among Fig. 1 (x) is not wondrous to the behavior of x.Yet because the existence of aqueous phase electrolyte (being salt ion), along with the increase of x, electromotive force typically reduces far faster than 1/x.The movable belt electron ion is used for the electrostatic field that part " shielding " or neutralization and charged " greatly " particle exist at a certain distance.The ion concentration of the oppositely charged that adds is larger, and is just higher in the potential shielding of any given distance of distance particle.

On the contrary, can by exclusion, cause approaching these Ion Phases on surface to lacking with the removable ion with particle symbol identical charges.Along with the increase of the distance of particle, the ion concentration of tape symbol opposite charges descends, and those ion concentrations with the same-sign electric charge increase so that they are reaching identical mean concentration away from the particle place, Ψ value drops to zero effectively herein.The electrolyte concentration that adds is higher, and Ψ (x) is sooner decay with the increase of distance x.Drop to the 1/e distance doubly of potential value on the surface at electromotive force, Ψ ₀Be typically expressed as 1/ Κ, wherein " the opposite shielding length " of Κ for drawing according to known Debye-H ü ckel formula.The Κ value increases based on the square root of electrolyte concentration (being assumed to univalent ion) with the increase of electrolyte concentration.The increase of electrolyte concentration causes the contraction (" thickness " that namely reduces, 1/ Κ) with electric double layer.

Charge interaction from the outward extending electromotive force of given electrically charged particle and adjacent particles carry produces repulsive force between two particles.Certainly, also have from the extended corresponding electromotive force of the second particle.Therefore, the electrostatic repulsion forces that exists between two particle is described to be caused by two " common factors " with electric double layer usually.The degree that two particles (perhaps, in fact, being with electric double layers for two) repel each other is by repelling potential energy V between particle _RCome analytical calculation, described at dlvo theory.As the V of two charged particle surface spacings from the function of x _RBehavior diagram in Fig. 2 (curve " V _R") show.

London-Van der Waals force that the interaction by electric dipole moment in two adjacent particles produces on the second basic impact that is suspended in charged particle stability in the aqueous medium.Because the random fluctuation of partial charge density, the dipole moment in particle is induced by the temporary transient dipole moment that forms in another particle.Interactional strength characteristic is to depend on the Hamaker coefficient that particle consists of.London-Van der Waals force is only interior effectively in relatively short distance, descends with the increase of interparticle distance x, and descends more fasterly than 1/x.That is to say, when not having significant electrolyte concentration, because the long range force characteristic of electrostatic repulsion forces between particle, London-Van der Waals force is faster with the respective attenuation that electrostatic repulsion forces between the attenuation ratio particle of distance increase shows.Generation is as potential barrier V between the charmed particle of interparticle distance function _AAlso diagram of behavior (curve " V _A") be shown among Fig. 2.

Therefore, be present in clean potential barrier V between two charged particles in the water slurry _TOTCan obtain by repulsion and the suction phase Calais of potential barrier between particle: V _TOT=V _R+ V _AThis result also diagram is shown among Fig. 2.Concerning very little x value---namely, when two particle effectively contacts---owing in spacing hour, comparing with the electrostatic energy of positively charged (repulsion), the London of electronegative (attraction)-Van der Waals potential barrier is substantially dominant, V _TOTValue is very large negative value.Along with the increase of spacing, because the effect of short distance attractive force reduces, clean potential barrier sharply raises.In these very little distance, in fact, agglomeration irreversibly occurs in particle---and namely, they have been absorbed in the dark energy " trap " of the minimum energy state that represents the 2-particIe system.Along with the further increase of distance, clean potential barrier finally reaches maximal value V _MAX, hypothetical particle has enough electric charges and shields electrolytical concentration enough, and this maximal value obviously is positive.At last, along with the further increase of interparticle distance x (that is, is supposed V _RImpact be large enough to and can avoid at V _TOTTo occurring the second minimum value among the figure of x), V _TOTFloat and decline, finally effectively be reduced to zero at very large spacing place.V _TOTDetailed behavior or shape to x depend on combination to form V _TOTTwo kinds of competitive potential barrier function V _RAnd V _AAmplitude and shape.

Potential barrier curve V between the clean particle that diagram shows among Fig. 2 _TOTTo the shape and size of x, determined disperse phase that specific charge is stable or emulsion through rapid lapse of time opposing agglomeration or coalescent after, can in fact keep stable.At V _TOTBe V to amplitude among the x figure _MAXPeak value consisted of energy between particle " shielding "; two kinds of charged particles of this energy " shielding " protection can be not each other too near (by Brownian movement; perhaps diffusion causes), strongly attract so that they irreversibly are absorbed in the dark energy wells that is produced by strong short distance London-Van der Waals force each other so as not to them.Because particle is in the aqueous phase diffusion of suspending liquid, they have the mean kinetic energy of kT magnitude, and wherein k is Boltzmann constant, and T is absolute temperature.Potential barrier V between particle _MAXHeight higher, they just more may be ostracised, and can not the degree to being enough to allow to occur irreversible agglomeration close to each other.Compare V with kT _MAXBe worth highlyer, the rejection area of " exclusive " around each particle is just larger, and to attempt at random to pass the possibility in this district just more infinitely small at every turn.

The check assessment that barrier height between particle was affected " half life period " of simplifying " emulsion " is useful, supposes that single drop is of a size of 1 μ m in oil/water ratio all for the moment.These assessments are by the people such as Fr iberg (" Theory of Emulsions(emulsion is theoretical) ", p.63) exist: Pharmaceutical Dosage Forms:Disperse Systems(pharmacy dosage Table: dispersant system), the people such as H.Lieberman (eds.), Vol.1, Marcel Dekker, New York(1998) in method calculate.The concentration of liquid drops of the simplification emulsion that draws is approximately 10 ¹¹Every ml.Half life period t _1/2Be defined as that the drop of initial number has half that agglomeration or coalescent needed time have occured in the emulsion.Population in agglomeration rate or flocculating rate and the per unit volume square, particle radii (being assumed to sphere) and their coefficient of diffusion be proportional.When lacking charge stability, thus when particle each other because STOCHASTIC DIFFUSION and freely colliding when producing irreversible agglomeration, the half life period was less than one second.The existence of potential barrier is used for slowing down the agglomeration rate between particle, thereby has increased the half life period.At V _MAX=5kT(T=25 ℃) situation under, t _1/2Only be increased to 38.2 seconds.Barrier height doubles between particle, reaches V _MAX=10kT causes t _1/2Significantly increase, even but only be 1.55 hours---typically to having shelf life for being not the several years, the final products that also must be a few weeks longer or several months are obviously inadequate.Barrier height doubles again between particle, reaches V _MAXDuring=20kT, causing the half life period is 3.91, approximately can satisfy many needs with product of commercial significance.(what is interesting is barrier height V between particle _MAX=50kT means that the half life period is 4.17 * 10 ¹³Year, really represented " stablizing " emulsion, and this moment, for example (every ml 10 ¹¹In) first pair of droplet coalescence need two days.）

Substantially, by dlvo theory, measure based on the independent of the amount of charge of being detained on the particle, with their size and electrolyte concentration, people can estimate the height (take kT as unit) of potential barrier between given electric charge-stable disperse phase or the particle of emulsion.Therefore, people can estimate the half life period of disperse phase or emulsion reliably substantially, and carry out the stability that " fine setting " reaches expectation by the chemical composition to product.Yet, the t of above summary is provided _1/2Same author to the barrier height assessment has obviously considered this theoretical method validity in practice pessimistically.(op cit, p.66) write: " calculating that contains the relative height of electrolytical shielding sees it is interesting from the viewpoint of science to the people such as Friberg, but is worth limited in daily preparation is attempted." they (p.70) op cit is also noted that the central issue relevant with evaluating emulsion stability---require a great deal of time to set up reliable conclusion." dilemma is this fact concerning the emulsion makers-up: the success of preparation only could be judged after one section long time.If shelf life needs 1 year, need substantially to wait 1 year ability to find whether a large amount of samples is still intact." this major defect also is Breuer in (" Cosmetic Emulsions(cosmetic emulsion), " p.420): Encyclopedia Of Emulsion Technology(emulsion technology encyclopedia), P.Becher(ed.), Vo l.2, Marcel Dekker, New York(1985) in the institute emphasize." predict long-term stability by the quickening lab investigation and remain the target that is difficult to ponder.Although the commercial significance that it is huge has only been finished a small amount of fundamental research to this problem.Undoubtedly, be because the result verification of any new forecasting techniques all needs one period considerable time (for example, the shelf time in 2 years) to one of relatively low reason of this problem interest.”

The shortage of the basic comprehension of the variable of coalescent in the emulsion on affecting (being instability) beginning is existed by Wa lstra: Encyclopedia of Emulsion Technology(emulsion The technology encyclopedia), P.Becher(ed.), Vol.4, Marcel Dekker, New York(1996) in emphasize (" Emulsions Stability(emulsion stability), " p.56)." by the above-mentioned discussion of this chapter, may be obviously, even relatively simple colloid resembles (naked eyes are visual) emulsion, also be inadequate for the understanding of its stability.About the interactional energy of colloid and on the impact of agglomeration rate many uncertainties are arranged.Especially need further research coalescent, wherein should change difference respectively and study.And, need to more study the part is coalescent, although its Main change has been proved and has determined their importance.What usually run in practice is very difficult especially in conjunction with instable advance notice, although attempted in some cases carrying out instable like this advance notice." Walalstra(op cit, p.119) continue with regard in addition relevant emulsion in the uncertainty of meaning of coalescent existence make a speech." what can reach a conclusion is that coalescent quantitative importance is unknown.It may be substantially variable, and may be the major reason that there is difference in the drop size aspect that utilizes the different surfaces activating agent to find.Because in the coalescent droplet that may occur in new formation, main according to fluid condition and disperse phase still less, this idea can exist consistent with critical droplet (larger droplet can fragmentation) size apparent.”

About " complexity " (being multicomponent) emulsion, the deficiency such as the knowledge of the basic interaction phenomenon in the milk proem system is existed by the people such as Euston (p.940): J.Food Sci, Vol.65, pp.934-940(2000) in recognize." two emphasis are emphasized in this work.The first, when attempting to predict the emulsification feature of the milk proem in the food systems, the use of very simple system may be substantially imappropriate." " the second, although the interaction of milk proem can have very large impact to the emulsification feature of milk proem, we to which interaction be important, how they occur, and can how to utilize their knowledge still to have blank.Need to carry out systematic research to this field, utilize this information to come as application-specific selection component better to allow us.”

The importance of emulsion stability is obvious unhelpful with the stability test of quickening, for Weiner(" Introduction(introduction), " p.9): Pharmaceutical Dosage Forms:Disperse Systems(pharmacy dosage form: dispersant system), the people such as H.Lieberman (eds.), Vol.1, Marcel Dekker, New York(1988) in the institute emphasize." coalescent is that all relevant groups are all flagrant, and it is at the function of the lip-deep emulsifying agent film strength of drop, that is to say the interfacial free energy potential barrier.The factor that affects coalescent factor and affect emulsion fluid is visibly different, only is difficulty and with fraudulent to the coalescent stability test of accelerating." he continues to claim: " and about the coalescent advance notice property testing of emulsion or irreversibly solve this query, promote seldom on evidence this system head and shoulders above its will in market produces, run into to the useful any authentic communication of storage life prediction.In addition, the overstress of system has produced the danger that is discarded in substantially acceptable preparation under the current conditions.”

The people such as Friberg (op cit, pp.70-71) have drawn their pessimistic assessment conclusion, admit that quicker, reliable method of testing is non-existent.If " found the reliable method of accelerating test, this problem can be avoided; That is to say, if a kind of method is available, then so that judge that according to short term variations long-term action becomes possibility.Unfortunately, do not obtain such conventional method.Using the many methods of going stable process that can accelerate the emulsion of particular types, and these methods are useful in their application.On the other hand, in the time of outside being applied to the field that they have set up, these methods may provide these material facts of fundamental errors result and can not overemphasize.”

By above-cited reference, obviously, open question is to need a very long time to determine that given emulsion or disperse phase be whether stable and to what degree in this field.Therefore, carried out making great efforts to accelerate the test process of stability.The trial overwhelming majority in past concentrates on the mode of accelerating the instable beginning of potential disperse phase around three kinds: (usually being fully) temperature 1) raises; 2) induce strong shearing force by mechanical hook-up; And 3) by sample is carried out centrifugal filtration, accelerate precipitation or its floatability than macroparticle/drop.Although these diverse ways are useful, their overwhelming majority can not be clearly and/or are as one man produced reliable quantitative information about the degree of stability of given emulsion or disperse phase, and perhaps how it comparing qualitatively with the known standard items of performance.

About the ultimate principle of " thermal stress ", DLVO has instructed the stability of disperse phase or emulsion will be along with barrier height V between particle _MAX(with respect to fixing kT value) descends and worsens.Therefore, for V _MAXFixed value, rising temperature (being the disperse phase of phase anomalous numbers) will produce identical result---the stability of reduction.Therefore, the degree of disperse phase exhibit stabilization sign (beginning that for example, is separated in oil-in-water emulsion) is relevant with the rising of temperature.Temperature on the impact of chemical reaction (being the Arrhenius equation) speed and thus on disperse phase particularly the impact of the stability of pharmaceutical preparation be the role of Newton(The Role of Temperature in theLife of a Pharmaceutical Preparation(temperature in the pharmacy set-up procedure)): Pharmacopeial Forum, Vol.25, #1, pp.7655-7661(1999 January-February) in comment, and at Vol.25, #4 revises in (in July, 1999-August) in p.8627.

The people such as Kwan are in US Patent No. 5,378, have described with the rising temperature in 609(1995) and have simulated being used for carrying out the aging impact of the reagent that contains emulsion of lipase chemical examination.Indication is the substantially light absorption of unaltered composition and active stable emulsion liquid formulation in 12 days under 57 degrees centigrade thermal stress, ensconces the 4 degrees centigrade of light absorption in 4 years with normal reservoir and equates.This behavior is completely contradicted with situation about observing for unsettled Quality control, and the latter stores in the time of 4 degrees centigrade and just began degraded in 7 days, and has shown immediately the increase that absorbs in the time of 57 degrees centigrade, shows to begin precipitation.

The people such as Faure are in US Patent No. 6,347, have described in 884B1(2002) a kind ofly for determining the method for hydrocarbon hydrogen compound emulsion about the temperature stability that is separated, are included in the crystallization of paraffin in diesel oil under a certain temperature.Beginning of being separated is used for improving weight change burning efficiency, that part immerses the gravimetry sensor in the oil water mixture by monitoring and detects.

The people such as Garver are in US Patent No. 6,263, have described the on-line sensor of using based on UV-visible absorption and/or scattering in 725B1(2001) to detect and differentiate colloidal material, for example pitch or the wood gum in paper pulp or paper process water.The optical attenuation of the colloid admixture of carrying out under two or more temperature or the difference of scatterometry or ratio provide the tolerance of the stability of disperse phase with respect to temperature.Provide the method for a kind of differentiation based on the heterogeneity of colloid liquid to different samples in the difference of observing aspect the thermal stability.

The method that the rising temperature is assessed emulsion stability is also by the people such as Yoon (" Interfacial properties as stability predictors of lecithinstabilized perfluorocarbon emulsion(is as the critical nature of the stability prediction device of stabilise lecithin perfluocarbon emulsion) "): Pharm Dev Tech, Vol 1, pp.333-41(1996) the middle utilization.Be used for Pluroni cF68(non-ionic surfactant) oil-in-water emulsion help stablize oil droplet phase (machine-processed by steric hindrance) and EPC, so that additional electric charge (charge-mediated) stability between two parties to be provided.The stability test that heat power is accelerated carries out at 5,20,37 and 60 degrees centigrade, adopts multiple emulsion preparation and multiple particle size analysis method to detect that the PSD of drop changes after two months.Usually, as expection, reach the maximum needed fate " D of mean diameter that measures _MAX" descend along with the increase of temperature.Yet, under some temperature values that adopt, exist significantly in the observed various emulsion preparations to change.In the time of 60 degrees centigrade, " reach D _MAXFate " cycle changed to 14 days from 3 days; The unification in the time of 37 degrees centigrade of this cycle is 14 days; In the time of 20 degrees centigrade, should the cycle change to 21 days from 14 days; And should cycle overwhelming majority in the time of 5 degrees centigrade it be 21 days.Research is found, adds cholesterol (oil droplet that namely adds the charge packet quilt) and can improve emulsion to the stability of thermal stress---namely, it has prolonged the time period before detecting the PSD marked change.That observes under the temperature that the overwhelming majority adopts " reaches D _MAXFate " significant change, only emphasized with serviceability temperature stress as the relevant restriction of the method for the typical multicomponent emulsion stability of qualitative assessment.

Vadas(" Stability of Pharmaceutical Products, (stability of pharmaceutical products) " is p.641) at Remington: The Science and Practice of Pharmacy(science with put into practice pharmacy), Gennaro(ed.), Vol.1, Mack Publishing, Easton, PA(1995) in emphasize and accelerate the relevant defective of stability assessment with the rising temperature: " simply test for two kinds and be used to screen the emulsion preparation.The first, the stability of emulsion can be determined by being heated 50-70 degree centigrade, and measure vision to observe or check its total physical stability by nephelometer.Emulsion the most stable when usually heating is at room temperature the most stable.Yet this may not be genuine, and possibility is different because emulsion is in the time of 60 degrees centigrade from room temperature.The second, the stability of emulsion can be estimated by " coalescence time " test.Although this is a kind of coarse quantitative test, is useful for the overall difference that at room temperature detects emulsion stability.”

Above first of stating of Vadas be, in practice, thisly makes that simple method may have serious defective on the surface that the emulsion temperature fully raises.The stability of utilizing the principle of dlvo theory to assess emulsion may need the typical case of temperature to raise and may change even as big as causing emulsion self.Depend on the complicacy of its phase diagram, the rising of these temperature may obtain emulsion or disperse phase " conversion " are become obviously this result who does not expect very much of the system of " difference " (according to physical saying, comprising having significantly different PSD).This possible behavior and serviceability temperature variable seriously oppose as the desired target of means, and desired target is only to disturb the impact of clean repulsive interaction between adjacent charged particle or the drop, and the simultaneously feature of emulsion or disperse phase supposition keeps not changing basically.

The second method for assessment of emulsion stability is application machine stress---for example, with a kind of form or another kind of form it is carried out " shaking "---in order to make disperse phase or suspending liquid be subject to the effect of shearing force.The application of waiting until strong shearing force in the supposition will cause that the lower emulsion of stability demonstrates more coalescent quickly than the higher emulsion of stability.For example, the people such as Degouy are at United States Patent (USP) 5,257, have described a kind of equipment in 528(1993), are used for aging at the closed circulation liquid circulation of the basis research of accelerating---for example, and for use in testing for the stability of the mud that uses in the oil drilling.Liquid is elevated to predetermined temperature and pressure, and faster speed circulation with than normal use the time, thereby produces higher shearing force.Liquid thereby stood accelerated deterioration, and only need the shorter time to disclose its rheological properties, and finally disclose its stability.

Yet, in practice, this relate to application machine stress accelerate the method for " simply " on the surface of stability test again be proved to be full of uncertain and difficult.Inherent limitations in the method can be understood by looking back two communications between the vein emulsion pharmaceutical manufacturer, it issues editor's (" pharmacy and antibiotic difference between the Pharmaceutical and antimicrobial differences between propofol emulsion products(Propofol emulsion product) with the letter form "), be published in recently Am J Heath-SystPharm, Vol.57, pp.1174-76,1176-77(2000).

In the first envelope letter, the people such as Redhead have summarized the best brand of product to them, are used for Intravenous Anesthesia and calm purpose, contain the result that physically stable property testing (acutely shaking) that the 10% stable soybean oil-in-water emulsion (pH6-9) of phosphatide of 1% Propofol accelerates obtains.A kind ofly shake at 270 times/minute " twisting action " of lower operation up to 16 hours shake the mechanical stress that is used to provide for emulsion prolongation.Some particle size analysis technology are used to assess as the PSD that shakes the duration function and change.The result is compared with those results that derive from common " equivalence " product (pH4.5-6.4).After 16 hours shake, do not occur yet measurable variation with this best brand of product and compare, shaking in time of two hours large (〉 the 2 μ m of mill run diameter) the percent by volume of oil droplet shown larger variation.The relatively relatively poor stability of mill run is owing to its lower pH, and its expection can make the surface negative charge (and corresponding zeta potential) of the stable oil droplet of phosphatide reduce.

In their letter in reply to people such as Redhead, the people such as Mirejovsky have argued the validity of shaking test for the reliable tolerance that provides emulsion stability.They quoted as proof inconsistency in the mechanical raking method (that is, and the vibratory movement of in research more early, using of people's references such as Redhead, its with respect to reality in relevant the moving up and down of twisting action bobbing machine used).They have also further quoted the people such as Hansrani as proof and have existed J.Parenter Sci. Technol., Vol 37, the more early stage work in pp.145-150(1983) admits that vibratory movement can cause emulsion to separate, if but preparation through sterilization after, it probably resists the dispersion of being induced by vibration.The people such as Mirejovsky sum up: " explanation of these examples, under realistic situation, can not set up forever excessively shake and the stability of emulsion between association.”

Although have the relevant potential challenges of above-mentioned mechanical stress application with being used for the assessment of quickening disperse phase and emulsion stability that quote as proof, still developed certain methods and device and realized such test process.A kind of apparatus and method for assessment of the emulsion phase transformation, are described in 958(1994) at United States Patent (USP) 5,319 by people such as Date.The part of emulsion is applied on the slidingsurface, and promotes against slidingsurface on another surface of test period.A sensor device is measured in glide direction and is applied to the lip-deep power that promotes.The variation of the power that records allows the phase transformation of assessment emulsion.The people such as Joseph are at United States Patent (USP) 5,987, have described a kind of method and apparatus in 969(1999), and it has described the feature of emulsion dynamic stability (namely in flow process).Supply with emulsion by the gap that defines between the inherent static surface of test container and the moving surface.Thereby can based on the circulation of the test container of flowing through, the dynamic stability feature of emulsion be described.

Lamar, the people such as III be at United States Patent (USP) 3,950, described the method for the stability of the edible emulsified liquid that is used for determining following themselves preparation in 547(1976).In these methods the earliest, method that complicacy is minimum only comprises " observing and the wait method ".Fractionation of fatty, water-rich phase and the rich oil percentage volume mutually that forms at the different elapsed-time standards interval later from 1/2nd hours to 40 hours, transparent fractionated container is visual to be determined by using.Other method relates to thermal stress and mechanical stress all is applied on the emulsion.By 71 degrees centigrade the time with sample heating two hours, then the sign that is separated of visual estimation is determined thermal stability.By sample is stirred in Waring mixer high speed (3200r.p.m.), and then its shear stability is determined in visualization.

Centrifuge method is the third method at the basis test emulsion stability of accelerating of early listing.P.641) Vadas(op cit has commented on centrifugal use to the assessment emulsion stability, supposes that wherein drop has than the lower density of water on every side." ultracentrifugation also can be used for determining emulsion stability.When the oil mass of separating is mapped to centrifugation time, just obtained a plateau curve (plateau curve).When with respect to the centrifugal revolution of per minute square to the mapping of oil float (become breast) rate the time, just produced linear graph.Its floatability is represented by the logarithm straight slope that each time mapping of rotating produces to per minute of emulsion-water boundaries to the distance of rotor center." after emulsion-water boundaries gradually changes in time, typically under different velocities of rotation, measure the radial distribution as the turbidity of the function of time.With same required the comparing for a long time of simple (gravity) precipitation/floatation device based on turbidity of use, centrifugal use is used for greatly shortening obvious oil float (becoming newborn) the required time that reaches.Yet centrifugal method has at least a serious latent defect.The fractional precipitation of hanging drop or floating behavior cause the local concentration of these drops to have greatly changed.That is to say, in emulsion, form over time large oil concentration gradient.Based on the detailed characteristics of phasor, with respect to leniently disturbing, substantially might so that emulsion in characteristic aspect generation significant change.This potential problem has reflected top Vadas(op cit, the contingent thing because the transition of temperature raises of p.641) inferring.

At last, the people such as Kanicky (" surface chemistry in the Surface Chemistry in the Petroleum Industry(petroleum industry), " p.257): Handbook of Applied Surface and colloidal chemistry handbook that Surface and Colloid Chemistry(uses), Holberg(ed.), Vo l.1, John Wiley and Sons, Ltd, West Sussex, UK(2002) in proved in the emulsion technical know-how at present existing gap.(op cit, p.257) write: " very obvious, emulsion is very complicated system to the people such as Kanicky.In the theoretical research of the complicacy of attempting to clarify these systems, obtained progress.Yet the advance notice of the type of most emulsions and stability more is to come from empiric observation, rather than comes from theory.The emulsion preparation still is considered to a kind of technology in many industrial cycles, rather than scientific approach." in recent years, attracted to the shortcoming that disperse phase exists in learning in the assessment that the researcher of the different field work of emulsion technology does and come.For example, the people (op cit, 2002) such as the people (opcit, 2000) such as the people such as Euston (op cit, 2000), Mirejovsky and Kanicky all confirms in the progress that has obtained less aspect the emulsion stability that theoretical model is applied to observation.These models comprise that those are Breuer(op cit, 1985), people (op cit, 1988) and the Walstra(op cit such as Friberg, 1996) model that is applied to actual emulsion inquired into.

Summary of the invention

It is a kind of more reliable and quantitatively determine the method and apparatus of disperse phase and emulsion stability that one object of the present invention is to provide.

Another object of the present invention has provided such method and apparatus: when with prior art discussed above in the instruction with the practice technology compare, significantly accelerate the instable beginning of disperse phase and emulsion.

For this reason, the present invention has instructed to accelerate a large amount of particle aggregation effects and has begun, and particularly come mode that the sample of disperse phase or emulsion is exerted pressure by reducing in disperse phase or the emulsion height of energy barrier between the particle between the particle, in sample dispersion phase or emulsion, described energy barrier has suppressed the adjacent particles degree to be enough to occur irreversible agglomeration owing to strong short distance attraction force acts closer to each other with the physical chemistry stress application.

Then, in a preferred embodiment of the invention, adopt highly sensitive quantitative detector, such as single-particle optical sensor (single-particle optical sensor, SPOS), determine the stability of disperse phase or emulsion by the increase that detects the particle aggregation effect.Highly sensitive like this quantitative detector produces particle size distribution (PSD), described particle size distribution shows particle concentration as surpassing the normal grain range of size and greater than the function of the major diameter separator particle afterbody of normal size, described separator (outlier) particle is as the indication of particle aggregation effect in disperse phase or the emulsion.

Can use and put on one of three kinds of dissimilar stress factors on the sample.The first, stress factor reduces the electric charge of particle surface by the pH that changes sample.When particle had net negative charge, stress factor was a kind of acid or buffering acid that sample pH value is reduced that join.When particle had clean positive charge, stress factor was a kind of alkali or buffer base (BB) that sample pH value is raise that join.

The second, the electrolyte that stress factor passes through to add absorption allows the particle from separating of suitable electric charge to be adsorbed onto on the particle surface to sample, reduces the net charge on the particle surface.When particle has net negative charge, from the electrolyte that adds from the positively charged ions binding of separating to particle surface, and reduced the net charge on the particle, thereby reduced the height of potential barrier between particle.When particle has net negative charge, from the electrolyte that adds from the electronegative ions binding of separating to particle surface, reduced equally the net charge on the particle, and reduced the height of potential barrier between particle.

The 3rd, the stress factor partly shielding effect Coulomb repulsion between charged particle, thereby accelerated the agglomeration of particle.This stress factor applies as simple monovalent salt, for example sodium chloride, perhaps divalence or trivalent salt.

In the preferred embodiment that detects particle aggregation effect increase, at the measurement sample or after from one batch PSD in the sample, calculate the number percent (PDP) of disperse phase by the PSD of each measurement.Then calculate the time dependent PDP rate of change of each stress factor level.Then, derive its figure of merit (FM) according to the time dependent PDP rate of change of given applied stress factor level.According to the observation, stable dispersion phase or emulsion will have the FM value of less, and poor quality, unstable disperse phase and emulsion will have relatively large FM value.

The FM value of sample can otherwise obtain.Can calculate the increase of the PDP that changes for per unit in the stress factor level of given elapsed-time standards value, then derive FM value the PDP that changes from the per unit for the stress factor level of given elapsed-time standards value increases, suppose that elapsed-time standards is sufficiently long to the degree that allows to accelerate instability and obvious particle aggregation effect to be set up.For given elapsed-time standards value and the stress factor level that applies, the FM value is larger, and sample is more unstable.

The FM value of sample also can derive from the combination that increases with the PDP rate of change of elapsed-time standards and the PDP that changes for per unit the stress factor level of given elapsed-time standards value for the given applied stress factor level.

In one aspect of the invention, stress factor applies with the amount that increases progressively continuously with the interlude interval, thereby produces the stress factor level that increases progressively gradually, and the step that the effect of duplicate detection particle aggregation increases after each stress factor increases progressively.

In another aspect of this invention, sample is divided into several batches.The varying level of stress factor is applied to each corresponding batch.Measure the increase of each batch particle aggregation effect, and this measurement is preferably the PSD measurement of each batch behind elapsed time section Δ t.The increase of particle aggregation effect also can detect in each batch after stress factor is applied to each batch immediately.The control batch that does not have the stress application factor can be provided, and if increase is arranged, the increase of the particle aggregation effect in the control batch behind elapsed time section Δ t, detected.

Alternatively, high sensitivity detector comprises one not in response to the detecting device of single particle in the sample.This detecting device is read one in response to the value X of the particle that passes the given area in the given interval.This value X can be in response to the tolerance of the optical attenuation of sample dispersion phase or emulsion turbidity, perhaps the tolerance of the light intensity of the given angle scope scattering of sample dispersion phase or emulsion particle.

Device of the present invention is used for carrying out the step of method of the present invention.This device uses and disperses pump that disperse phase or the emulsion sample of test are fed in the test container, perhaps supplies to several test containers as different batches.Another disperses pump as discussed above, the sample of supply stress factor in the test container.Then the sample of in the future self-test container is provided by the detecting device that detects particle aggregation effect increase.In one embodiment, detecting device is a kind of single-particle analyser, SPOS for example, and it may comprise the PSD of the major diameter separator particle afterbody of indication particle aggregation effect degree.This device is conducive to calculate the rate of change of PDP, PDP and PDP that the horizontal per unit of stress factor changes increases, and according to the value of these data derivations FM.In a second embodiment, detecting device is read one in response to the value X of the particle of the sample dispersion phase of passing the given area in given interval or emulsion.This value X can be in response to the tolerance of the optical attenuation of sample dispersion phase or emulsion turbidity, and perhaps X can be the tolerance of light intensity of the given angle scope scattering of sample dispersion phase or emulsion particle.

The inventive system comprises a computer control/processor, it is suitable for being programmed control pump, to the running of the sample flow of one or more test containers and stress factor stream, sensor and regularly, and according to calculating and the processing of the data of the inventive method.

Description of drawings

With reference to accompanying drawing, can understand more fully these and other objects of the present invention, feature and advantage, wherein:

Fig. 1 diagram has shown " electric double layer " or as arriving the electrostatic potential barrier of particle surface apart from the x function, (electromotive force is Ψ by particle for they ₀) on electric charge and the movable belt electron ion of aqueous phase produce;

Fig. 2 diagram has shown clean potential barrier V between particle _TOT, it has by attracting potential energy V _AWith repulsion potential energy V _RThe barrier height V that forms _MAX

Fig. 3 diagram has shown that supposition attracts potential energy V _AWhen immobilizing, owing to repelling potential energy V _R(curve V _R1And V _R2) increase of intensity, barrier height V between particle _MAX(curve V _TOT1And V _TOT2) gradually increase;

Fig. 4 A diagram has shown the particle size distribution (PSD-# particle and diameter d) (solid line-" 1 ") of stable disperse phase or emulsion, and after the obvious unstable beginning (dotted line-" 2 "), causes particle aggregation effect or droplet coalescence;

Fig. 4 B has shown that particle or liquid-drop diameter are greater than measuring threshold value d ₀The amplification of macroparticle " afterbody " of PSD represent, it derives from stable (solid line-" 1 ") and the SPOS of unstable (dotted line-" 2 ") disperse phase or emulsion of (# particle and diameter d) among Fig. 4 A;

Fig. 5 has shown the number percent (v/v) of the disperse phase (d〉1.8 μ m) of the whole milk's (pH is unchanged) who obtains over time three " contrasts " batch, perhaps " PDP ": " 0608 ", perhaps batch #1(black circle); " 0612 ", perhaps batch #2(closed square); And " 0615 ", the perhaps solid triangle of batch #3();

Fig. 6 has shown the whole milk's who obtains over time after the application (t=0) of acid stress (pH=6.1) three batches PDP(d〉1.8 μ m): " 0608 " (black circle); " 0612 " (closed square) and " 0615 " (solid triangle);

Fig. 7 has shown the whole milk's who obtains over time after the application (t=0) of acid stress (pH=5.7) three batches PDP(d〉1.8 μ m): " 0608 " (black circle); " 0612 " (closed square) and " 0615 " (solid triangle);

After Fig. 8 has shown the application of acid stress (pH=5.7), derive from PSD(# particle/ml of the SPOS of whole milk batch #2 or " 0612 "〉1.8 μ m) the growth of macroparticle " afterbody ", corresponding to the four kinds of PDP values (closed square) that show among Fig. 7;

After Fig. 9 had shown the application of acid stress (pH=5.7), the gradually increase of the absolute volume number percent of whole milk batch #2 or " 0612 " (being PDP and d) was corresponding to the four kinds of PSD " afterbody " that show among Fig. 8 (d〉1.8 μ m);

Figure 10 has shown (t=0) after the application of lime chloride stress, the time dependent PDP(d that obtains for whole milk's batch " 0608 "〉1.8 μ m): 0M CaCl ₂, " contrast " (black circle), 0.005M CaCl ₂(closed square) and 0.01M CaCl ₂(solid triangle);

Figure 11 has shown (t=0) after the application of lime chloride stress, the time dependent PDP(d that obtains for whole milk's batch " 0612 "〉1.8 μ m): 0M CaCl ₂, " contrast " (black circle), 0.005M CaCl ₂(closed square) and 0.01M CaCl ₂(solid triangle);

Figure 12 has shown (t=0) after the application of lime chloride stress, the time dependent PDP(d that obtains for whole milk's batch " 0615 "〉1.8 μ m): 0M CaCl ₂, " contrast " (black circle), 0.005M CaCl ₂(closed square) and 0.01M CaCl ₂(solid triangle);

Figure 13 is (t=0) after the application of the in proportion version-lime chloride stress of compression of Figure 11, the time dependent PDP(d of whole milk batch " 0612 "〉1.8 μ m): 0M CaCl ₂(black circle), 0.005M CaCl ₂(closed square) and 0.01M CaCl ₂(solid triangle);

Figure 14 has shown lime chloride stress (0.01M CaCl ₂) application (t=0) after, PSD(# particle/ml that SPOS obtains for milk sample " 0612 "〉1.8 μ m) the growth of macroparticle " afterbody ", corresponding to the six kinds of PDP values (solid triangle) that show among Figure 13;

After Figure 15 had shown the application of acid stress (pH=5.7), the gradually increase of the absolute volume number percent (being PDP and d) that obtains for whole milk's batch " 0612 " was corresponding to the four kinds of PSD " afterbody " that show among Figure 14 (d〉1.8 μ m);

Figure 16 has shown what add (t=0) ionic species and goes stabilized mixture after 28 hours, the over time PDP(d of (with a hour expression, the most high in 1800 minutes) of the vegetable oil emulsification liquid that lecithin is stable〉1.8 μ m);

Figure 17 has shown behind the ionic species that adds (t=0) mixing and application sodium chloride stress, the time dependent PDP(d that obtains for the vegetable oil emulsification liquid of Figure 16〉1.8 μ m): 0M NaCl(soft dot), 0.05M the NaCl(black circle), 0.10M NaCl(closed square) and the solid triangle of 0.15M NaCl();

Figure 18 has shown behind the ionic species that adds (t=0) mixing and the sour stress of application, the time dependent PDP(d that obtains for the vegetable oil emulsification liquid of Figure 16〉1.8 μ m): pH6.56 contrasts (soft dot), the pH5.65(black circle), pH5.13(closed square) and the solid triangle of pH4.46();

Figure 19 diagram has shown that quickening of the present invention determines first embodiment of method of the stability of disperse phase or emulsion, it is by system applies stress factor " A ", comprise acid or alkali are added in the sample (any suitable sample), cause the net charge on the particle to reduce;

Figure 20 diagram has shown that quickening of the present invention determines second embodiment of method of the stability of disperse phase or emulsion, it is by system applies stress factor " B ", comprise that the particular electrolyte that will contain adion adds in the sample, cause the net charge on the particle to reduce;

Figure 21 diagram has shown that quickening of the present invention determines the 3rd embodiment of the stability approach of disperse phase or emulsion, and it comprises non-adsorbability salt is added in the sample by system applies stress factor " C ", causes interparticle electrostatic repulsion forces to reduce;

Figure 22 has shown the simplified mode figure of exemplary device, comprises the particle size analysis instrument based on SPOS, and it can be used for realizing that quickening described here determines any new method of the stability of disperse phase or emulsion;

Figure 23 has shown the simplified mode figure of exemplary device, comprises the technology that is different from particle size analysis, for example turbidity or light scattering, and it can be used for realizing that quickening described here determines any new method of the stability of disperse phase or emulsion;

Figure 24 A has shown PDP and the t behavior (solid-line curve, identical with Figure 18) of measuring, and it obtains for the vegetable oil emulsification liquid of using behind the sour stress, with the hypothesis behavior (dashed curve) that can be similar but slightly more stable sample acquisition;

Figure 24 B is identical with Figure 24 A, except PDP and the t behavior (dashed curve) of supposing is from obviously more stable than the sample of describing Figure 24 A sample obtains;

Figure 25 A has shown PDP and the t behavior (solid-line curve, identical with Figure 18) of measuring, and it obtains for the vegetable oil emulsification liquid of using behind the sour stress, with the hypothesis behavior (dashed curve) that can be similar but stable slightly poor sample acquisition; And

Figure 25 B is identical with Figure 25 A, except PDP and the t behavior (dashed curve) of supposing is from obviously obtaining than the more unsettled sample of the sample of describing Figure 25 A.

Embodiment

Motivation of the present invention is the needs for the universally recognized more reliable and quantivative approach of determining emulsion and disperse phase stability.More particularly, the present invention relates to a kind of new method of stability test, it provides and for example incorporated by reference above those and the result of the remarkable quickening that current operation technique that indirectly mention is relevant.New method to be described, is devoted to the obvious improved needs of long-standing test disperse phase stability, not only relates to fast determining, and relates to the raising of repeatable and predictive ability.

By the discussion of front, obviously, the stability of disperse phase namely stops and comprises that remarkable agglomeration or droplet coalescence occur the particle of disperse phase, and barrier height V between the particle that diagram shows among Fig. 2 _MAXClosely related.For given temperature T, with corresponding heat energy kT, potential barrier is higher, and the disperse phase of charge stable is also more stable, and therefore after making, occurs in irreversible particle aggregation effect or droplet coalescence (finally the causing being separated) time before also obviously elongated.

As previous comment, there are two kinds and can be used for increasing V _MAXThe fundamental mechanism of value supposes that the formation of particle and concentration are substantially constant, and thereby as attracting potential energy V between the particle of spacing x function _AAlso substantially constant.At first, can increase the charge-averaging amount that is adsorbed in particle/drop surface, thereby increase their lip-deep average potential Ψ ₀In fact, this action has the effect of " rising ", repels potential energy V between particle _RBe shown among Fig. 2 with the complete curve diagram of x (namely with respect to the V of all x values _RValue increases).As follows, two kinds of basic modes that increase the electric charge on particle or the drop are arranged.The second, can reduce the concentration of the removable ion of aqueous phase, thereby reduce each particle or drop the shielding of extended electric field.This action has V _RWith x curve " stretching, extension " to the effect of longer distance, thereby the permission repulsion electric double layer relevant with particle or drop more intersects or is overlapping.These two kinds of actions all have makes the effect that barrier height increases between clean particle, thereby can owing to the effect of strong short distance attractive force, not make the adjacent particles degree to being enough to occur irreversible agglomeration closer to each other.

Therefore, in practice, for the quantitative test of the quickening that realizes disperse phase stability, people can " conversely " use the principle of charge stable.The following describes for systematically reducing barrier height V between interested disperse phase particle _MAXMethod, accelerating the beginning of obvious particle/drop agglomeration, and in this process, draw the qualitative assessment of the stability/quality of these disperse phase.(op cit, the many example indications that p.63) calculate based on the degree (namely relevant with the kT value) that the energy barrier height reduces, can realize that emulsion or the drama of disperse phase half life period shorten such as the people such as Friberg by above-mentioned discussion.This sample stability provides the device of the method for the stability test that can design quickening to the strong dependence of barrier height, described device can be told metastable " example " (being sample) effectively from another substantially lower example of stability.

People often can in the face of two kinds of stability may be substantially different the example of disperse phase.The difficult problem that the typical case exists is, determining which kind of sample is reliable, clear and definite is more stable among both, and how long needs (difference based on sample typically is several weeks, several months or several years).P.70) and Breuer(op cit thisly be restricted to the people such as Friberg that early quote (op cit, p.420) emphasizes.Limiting factor is, the most unsettled sample must reach certain unstable level-namely, agglomeration or coalescent degree-it can be measured and quantize reliably.Fortunately, for example can develop the physical mechanism that provides every kind of sample stability, so that in the difference that discloses under the mode of greatly accelerating between them.Why a kind of stability of sample can finally be reduced to than the reason of the stability " good " of another kind of sample, and the energy barrier height of its energy barrier aspect ratio " inferior " sample is wanted large this simple fact.

Support the ultimate principle of new method to be inquired into to be, by one or more the disperse phase of discussing specifically is scheduled to increment, use one or more equally to specific " stress factor " (the following discussion) of the product of studying, reduce energy barrier height V between particle _MAX(that is, for giving fixed temperature).As a result, " inferior " disperse phase very fast " propelling " is to measurable instable beginning, in the situation that there is not the stress application factor, " inferior " disperse phase reaches this point sooner than more stable disperse phase.Randomly, other stress increment is applied in the disperse phase and allows quantitatively and to study in great detail its stable dynamics.

The continuous increment minimizing of repulsion potential energy is shown among Fig. 3 the diagram that affects of the energy barrier height of generation between particle.Before the stress application factor, " beginning " repulsive energy V of disperse phase _RBy the curve V among Fig. 3 _R1Indication.Potential energy is by curve V between clean (always) particle that produces _TOT1Show.(attract potential energy V _ABe shown in equally among Fig. 3, suppose to attract potential energy V _AInvariable, be not subjected to the impact of stress factor.) recruitment of the stress application factor causes repulsive energy V between particle _RReduce gradually---for example, from curve V _R1To curve V _R2As a result, the height V of potential barrier between particle _MAXAlso corresponding reduction---from curve V _TOT1To curve V _TOT2Therefore, the disperse phase stability that becomes reduces gradually, causes the particle aggregation effect to be accelerated.

Realize needing the second factor to exist for the new method of the stability test of accelerating.This is a kind ofly should be used for determining disperse phase the become sensitivity of unstable degree, quantitative method by means of one or more stress factors.Particle size distribution parameter (PSD) both had been used for solids and also had been used for drop, provided respectively particle aggregation effect or a kind of of droplet coalescence degree of occuring in the disperse phase reliably and directly to indicate on the principle.(term agglomeration used herein also refers to coalescent sometimes when liquid-liquid emulsion.) such as front indication, the existence of particle/drop agglomeration is the physics performance of the unstable degree of disperse phase; The trend of instability development is larger, and the degree of agglomeration is just larger.Therefore, the method for the most directly surveying the stability of emulsion or disperse phase has been set up in the measurement of PSD (comprising " sphere sizes distributes or GSD ").Fig. 4 A(solid-line curve 1) shown before obvious particle aggregation effect occurs the simplification of the PSD of metastable disperse phase or emulsion (stylizing) expression.Fig. 4 A(dashed curve 2) also shown after after a while, when the agglomeration of measurable amount has occured when-for example, after one or more specific stress factors are applied to disperse phase, the reduced graph of the PSD of same sample.If the increase of agglomeration is appropriate, show towards unsettled variation tendency very little, should be very little in the increase that the PSD of " afterbody " of major diameter " separator " particle changes to first approximation.

In practice, be used for determining enough sensitive variations to the less that can quantitatively detect the disperse phase agglomeration state of discussing of technology of PSD.If the enough sensitivity of variation shortage of the PSD that the technology that adopts pair is relevant with the increase of the less of particle/drop agglomeration, the ultimate principle that new method so of the present invention adopts may be inappropriate.In this case, the stress that is applied to disperse phase may need than allowing to detect desired large of the significant variation of PSD in order to produce enough agglomerations after the relatively short time.That is to say, need V _MAXThe little interference to disperse phase of relatively large reduction-no longer be supposition-, cause two kinds of potential problems.The first, the large stress of this supposition can cause " good " of disperse phase and " inferior " sample to become so unstable, so that they all present essentially identical significantly agglomeration within the very short time period.Then, even be not impossible, may also be difficult to quantize the quality of two kinds of samples-stable difference.Second, potential more it is disturbing, larger stress application is to disperse phase (described disperse phase has been born the risk that changes emulsion or disperse phase essential characteristic), so that when beginning, with respect to physical chemistry structure or feature, two kinds of samples to be compared are no longer closely similar.

Single-particle optical sensing technology, perhaps SPOS, be ideally suited the task that detection and the quantification PSD " afterbody " relevant with the less increase of numerous super large particle aggregation effect or coalescent ball increases, the effect of described super large particle aggregation or coalescent ball go stable commitment to produce at the disperse phase of accelerating.Why attractive SPOS technology (being also referred to as optical particle counting or OPC) is, and be to a great extent because it is so sensitive: namely, it is in response to the single particle in the interested range of size.When light passed separately the photosensitive area (OSZ) of a strict difinition, the physics principle of delustring (LE) or light scattering (LS) can be used for detecting and determining to be suspended in the size of particle in the liquid.In the LE method, the signal of generation comprises highly being Δ V _LENegative-going pulse, itself and relatively large background voltage level V ₀Stack.In the LS method, the signal of generation comprises highly being Δ V _LSDirect impulse, its ideally with the stack of zero background voltage level.In either case, suppose the sensor of suitable design, pulse height is with the particle diameter d monotone increasing.Therefore use predetermined Δ V _LEWith d or Δ V _LSWith d " calibration curve ", particle or drop can be determined its size by their ranging pulse height, and described calibration curve obtains by " standard " particle (typically being polystyrene latex) that uses some known homogeneous diameters.

Rely on the optical design of sensor, LE type SPOS technology typically provides maximum particle size range.A kind of representational LE type sensor, Model LE400-1.3(Particle Sizing System(particle size is determined system), Santa Barbara, CA) the normal size scope of 1.3 to 400 μ m is provided, and be suitable for ideally measuring the large diameter afterbody of small and large emulsion.(use this sensor to obtain result discussed below.) owing to there not being large background voltage V ₀, and the ability that increases the pulse height of given particle size by increasing the intensity of light source, by using the LS method detection threshold than low dimensional is significantly reduced.Yet in practice, LS type sensor lacks the upper dimension bound that adopts the LE method to be easy to obtain.If necessary, in hybrid sensor design, LE and the combination of LS method can be responded thereby can produce " add up " of being called " LE+LS ", such as people such as Wells at United States Patent (USP) 5,835,211(1998) described in.This method had both produced the lower limit of size, had produced again wide dynamic dimension scope (for example 0.5 to 400 μ m), and these features are to obtain separately by the principle of using LE or LS together.

With respect to the feature for generation of the standard particle of calibration curve, the difference of refractive index of the particle of research or the difference of the optical characteristics of drop-particularly must cause adopting " apparent " PSD that the SPOS technology obtains and actual or real inconsistent between the PSD.In the situation that adopt the LS method, this inconsistent may be quite large, if particle is different from the contrast of standard particle substantially with respect to the refractive index " contrast (contrast) " of surrounding liquid, then need to carry out Theoretical Correction.Fortunately be, utilize the LE method, concerning the interested sample of the overwhelming majority, the amplitude of response is much lower to the degree of dependence of particle contrast.The PSD of the measurement that therefore, obtains by SPOS-LE is usually as the reliable representative of the true PSD of sample.Therefore, the growth of the true PSD of sample of measurement " afterbody ", usually provide since the actual increase of the stress induced disperse phase unstable excessive agglomeration that produces or coalescent drop/spheroid quantity qualitatively and quantitative fine description.

Relevant other feature or the needs of many SPOS technology with being of value to concise and to the point discussion are arranged.The first, most interested disperse phase or emulsion highly concentrate, and in volume weight (v/v), its disperse phase usually is at least 1% of whole samples, and even sometimes up to 40% or 50%.Therefore, for fear of the great artefact (passing through simultaneously OSZ at the more than one particle that detects) who when measuring PSD, is caused by " chance " event, the abundant dilution of initial sample is always needed.The signal pulse of the merging that produces/distortion causes the systematicness expansion of ranging pulse height, thereby and causes compare large size offset in the PSD afterbody.As a result, can suitably increase the weight of the distortion (even not being whole) of PSD shape, also make the most diameter scope be higher than the threshold value d that SPOS measures ₀Therefore, concentrated sample must be diluted to the serious distortion that can avoid the PSD that measures before analysis, and avoids correspondingly producing in disperse phase (" PDP " will the be discussed below) percent by volume of calculating the required degree of apparent error.This diluting effect can be finished in several ways, and whether this depends on fixing, predetermined dilution gfactor suitable, perhaps whether expects automatic determined value.Automatically the example of the process useful of (perhaps fixing) dilution concentrating sample and device be the people such as Nicoli at United States Patent (USP) 4,794,806(1989) in and Nicoli at United States Patent (USP) 6,211,956B1(2001) described in.

The second considers, suppose that the fact is most (typically〉99%) to comprise that the particle of disperse phase is at d ₀Below, use the SPOS-LE technology, whether can be reliably, the large diameter afterbody of rational Measurement accuracy PSD-namely be higher than appropriate threshold d ₀Diameter d.Even are enough to be diluted to its concentration than macroparticle/drop and can guarantee that they once pass sensing area when interested, but these a large amount of less particles always pass through OSZ simultaneously.Fortunately be that concerning most of interested disperse phase, the existence of this " ocean " than small-particle is on the less that affects of PSD, as measuring by SPOS-LE (assumes samples is fully diluted).About measuring the needs of PSD afterbody, this helps to form a kind of in its significant inherent feature.For having enough contrasts greater than about 5 μ m(supposition) but less than the particle of the thickness of OSZ, pulse height Δ V _LESquare proportional with diameter roughly.When particle became more and more less and reach the wavelength X of light source, the physical mechanism of being responsible for delustring became light scattering by simple how much refractions, is described by the Mie scattering theory.Pulse height approximately descends rapidly with the speed of 4 powers of the d that reduces.At last, in " Rayleigh zone " than small-particle-namely, d＜＜λ (≈ 0.7 μ m is for typical sensor)-pulse height drops to the degree of 6 powers of d.For all attempts and purpose, even these a large amount of particles are measured effectively by SPOS-LE and are ignored.

Therefore, in practice, although with interested than macroparticle (d〉d ₀) quantity compare, the common enormous amount of particle of the size reduction by OSZ, but can ignore on the impact of PSD afterbody is as SPOS-LE is measured.Certainly, this deduction supposition sample suspension has been diluted to the suitable degree that enough reaches.This effective irrelevance than small-particle can be confirmed by again measure the PSD afterbody under low concentration.If the dilution that initial measurement is chosen is suitable, will be basic identical and overlapping each other with the PSD afterbody of the population in every milliliter of initial sample (#) expression.Certainly, this be equal to because the not enough statistical fluctuation that produces of the number of particles of intended size to be counted is irrelevant---the full-size when measuring minimum particle is relevant usually.

By above-mentioned discussion, obviously, by means of the high sensitivity (typically secondary or higher) that its single-particle decomposes and particle size is changed, the SPOS-LE technology can well be suitable for determining the increase of the less particle aggregation effect relevant with instability quickening in the disperse phase.In content of the present invention, the distinct disadvantage of this technology---namely, when particle substantially less than measuring threshold value d ₀The time---the shortage of its sensitivity has become unique advantage." part PSD " determine-is afterbody, d〉d ₀, only so that final measurement is more sensitive to the little variation in the fraction of whole distributions (that is, having represented than macroparticle/drop).The subtle change of quantity, perhaps even now larger with the volume fraction of the PSD tail dependence of measuring.Therefore, with respect to other significant response " comprehensively " technology in all particles that comprises disperse phase, " gain (gain) " of SPOS-LE detection technique fully increased.Therefore, the SPOS technology can with among Fig. 4 A with respect to the little absolute change of the PSD shown in the sample " 2 " of sample " 1 ", be transformed into much bigger relative variation (d〉d ₀), see Fig. 4 B.

Although be used for to realize the SPOS technology of the inventive method significant advantage is arranged, recognize also can effectively adopt other to be used for the particle size analysis technology to characterize the number change of the particle aggregation effect relevant with the unstable beginning of sample very important.A kind of the substituting of SPOS is same technology in response to single particle-" resistance hole " method, also because of its trade name " Coulter Counter ^TM" or " Multisizer ^TM" (Beckman-Coulter Corp., Hialeah, FL), and " Electrozone ^TM" (Particle Data Inc., Elmhurst, IL) and well-known.The particle that is suspended in the conducting liquid (being that water adds electrolyte) slightly once passes a very little hole, causes that the resistance moment by the latter increases.The height of the negative-going pulse in the electric current that produces is ideally along with particle volume moment increase.Compare with SPOS although compare its major advantage (namely relative insensitive to the optical signature of particle) with SPOS, resistance hole technology has many shortcomings.These shortcomings comprise: need the relatively concentrated electrolyte level of aqueous phase, to the neurological susceptibility stopped up, relatively low particle counting rate and the dynamic dimension scope of less.The below will find out the first shortcoming especially severe in these shortcomings, suppose systematically to add salt and consisted of an important embodiment of the present invention in interested disperse phase.

Can consider with other the particle size assay method with the following describes systematically go stable method to be combined with to sample.The most common example of replaceable technology is those technology based on " comprehensively " method-namely, can be simultaneously effectively in response to the particle of all sizes.An example is dynamics light scattering (DLS), is also referred to as photon correlation spectroscopy (PCS).Random Brownian movement by being suspended in particle in the liquid or the interim fluctuation of the scattered light intensity (with given scattering angle) that diffusion causes can adopt the intensity autocorrelation function to analyze.By one or more algorithms, the latter arithmetically is being " reversible ", the PSD that obtains estimating.Another kind of potential possible technique is " laser diffraction ", the physical technique, i.e. wide-angle Mie scattering and the forward angle Fraunhofer diffraction that generally include two kinds of combinations or use respectively.Adopt suitable algorithm, based on the diffracted intensity " pattern " of angle again " conversion ", draw the PSD of estimation.The polytechnic another kind of example of the particle size analysis of the method that can consider to realize that the present invention instructs is ultrasonic attenuation.The variation that ultrasound wave is propagated by a certain amount of sample when when suitable transfer algorithm is combined, can be used for obtaining the estimation of PSD as the function of wavelength.

Understanding exists relevant with the measurement of particle size itself abnormally this fact of other analytical technology very important, and it can be used for realizing method of the present invention effectively.All need is these variations in response to particle aggregation effect (or droplet coalescence), have enough sensitivity and reproducible substitute technology, and described particle aggregation effect produces (as described below) by the disperse phase that one or more stress factors are used for studying.An example is known classical light scattering technique.Usually the light beam that is produced by LASER Light Source passes the sample (namely avoiding because multiple scattering causes the artefact) of debita spissitudo.Be collected in the sensing volume of restriction simultaneously by the light of relatively a large amount of particle scattering, and detect its suitable angular range, choose ideally described suitable angular range and produce the signal response of monotone increasing along with " afterbody " growth of the macroparticle agglomeration relevant with unsettled beginning.Therefore, scattering strength provides " representative " of the actual PSD that other technology (comprising integrated approach) of adopting SPOS or some to carry out particle size analysis directly draws.

The second example that can be used as the representative technology of particle size analysis device is the straightforward procedure of turbidometry or spectrophotometry.Suitably the light beam of wavelength or wavelength coverage passes the fluid sample of given thickness (being optical path length) and debita spissitudo.The degree of beam intensity decay is relevant with potential PSD.Suppose the optimizing optical design, the turbidity of sample or optical density be the monotone increasing along with the variation of " afterbody " of the macroparticle agglomeration relevant with unsettled beginning ideally.Turbidimetric analysis turbidimetry and light scattering technique can be regarded roughly as complementation; That is to say, along with the increase of particle aggregation effect, the former transmitted intensity reduces, and the strength increase relevant with the latter.

Although these and other complex art has been effectively applied in many samples based on particle, can prove that these complex arts are little to the method use that realization the present invention instructs.Compare with SPOS, these complex arts are inevitable more insensitive to the less variation of the quantity of particle aggregation effect, suppose that the fact is that (in essence) these complex arts are in response to the particle of all sizes that comprise disperse phase (in the relative dimensions scope).Yet, depending on the specific disperse phase of research and the stress factor of employing, the variation that these technology that substitute can be proved to be PSD has enough sensitivity.Under any circumstance, discussed below for explaining that the example that method of the present invention is chosen relates to the PSD afterbody that the SPOS-LE technology is used for measuring two kinds of different miniature emulsions.Therefore this just means or infers and do not lose general character.

For the predictive ability as subject methods of the present invention is described, it is useful to the response of various stress factors that specific disperse phase and emulsion are discussed.In these examples, we have selected representative to disturb barrier height between particle, in order to accelerate the unsettled beginning of these disperse phase with system mode, and identify thus the particular condition of the different mechanisms of substandard products.Such mechanism comprises by changing pH-for example " sour stress ", reduces the surface charge on particle or the drop.This is to be determined by the type of the emulsifying agent that is used for systems stabilisation or surfactant with acid or with the decision that alkali stress is applied in the given disperse phase.For the stable dispersion phase that contains electronegative particle (for example, coated by anionic surfactant in typical 6.5 to 9 pH scope), the acid of adding (causing pH and surface charge all to reduce) is a kind of suitable stress factor.On the contrary, for the stable dispersion phase that contains positively charged particle (for example, coated by cationic surfactant in typical 4 to 6.5 pH scope), the alkali of adding (causing pH increase and surface charge to reduce) is a kind of suitable stress factor.Be used for the second mechanism that the inducible system instability accelerates and comprise that ion by selective adsorption band contrary sign electric charge reduces surface charge-for example " the lime chloride stress " on particle or the drop.At last, be used for reducing the third mechanism of repelling potential energy between particle and comprise that the charged ion with motion joins system-for example " sodium chloride stress ".The electrostatic field that causes repulsive force increase between particle that the ion of the non-absorption of these of aqueous phase, free diffusing is used for existing between the shielding charged particle.

Systematically stress application is milk-fat emulsion-namely with the first example of the product that allows successfully to accelerate stability test, full-cream (homogenizing) that can buy from the market.Full-cream is a kind of oil-in-water emulsion, and it contains the butterfat that is scattered in the water and drips.Fat drop shows the caseic protein of ox of its preliminary emulsification by (about 23,600 dalton) of coated a kind of intermediate molecular weight, via its ionization with the amino acid head group of negative ion, this fat drop is by charge stable.Except applying net negative charge in fat drop, thereby provide outside the Coulomb repulsion of drop inside, casein molecule can provide anti-coalescent additional stability by steric hindrance mechanism.The milk of buying on the market has the storage life in about two weeks usually.The quality of homogenous disperse phase can adopt simple sense organ to estimate to come qualitative evaluation.Whether these assessments are included in visually from disperse phase butterfat and obviously separate with continuous water in bulk, and/or whether foul smelling distinguish the flavor of and/or mouthfeel not good, namely be with the finished product of " tart flavour ".The tart flavour of milk shows the failure of dispersion, and it is consistent with the term of validity (ED) on being printed on container or occur immediately after it to it is desirable to the generation of this situation, although this situation is extremely rare in practice.

Studied the whole milk from three different batches of single manufacturer, and identified-specifically June 8 (" 0608 "), June 12 (" 0612 ") and June 15 (" 0615 ") by their ED.As a reference point, for the first time research starts from respectively 1 day, 5 days and 8 days before the storage period of batch #1, batch #2 of manufacturer's appointment and batch #3.For each experiment, by being separated of visual inspection product, and judge whether that by sense of smell foul smelling exists; Check by pH; And by measuring major diameter (〉 1.8 μ m) the PSD afterbody check described product.Utilization is based on single-particle optical sensing (SPOS) technology or " SPOS-LE " (AccuSizer of delustring ^TM780/APS, Particle Sizing Systems Inc., Santa Barbara, CA) realize the dimension analysis of particle.In all cases, the result is with greater than 1.8 microns (scopes: volume-percentage by weight (" the PDP ") expression of fat drop 1.8-50 μ m) in disperse phase.Each batch of three batches of whole milks carried out two kinds of different researchs, and studied the effect of different stress factors.

The purpose of the first research is, assesses " pH stress " to the impact of whole milk's stability.By to this common pH=6.5, add acid and stress application by the stable electronegative disperse phase of ox casein, the surface charge that causes small dispersion butter oil to drip reduces, thereby induces agglomeration.Employing is by 0.1M(21.01g/L) citric acid monohydrate (C ₆H ₈O ₇H ₂O) and 0.2M(28.44g/L) ADSP (Na ₂HPO ₄) the formulated standard buffer solution of stoste (stock solution) milk of each batch is carried out acidifying.Every kind of stoste of designated volume added together to be mixed with the pH value with expectation be 6.1 and 5.7 final buffer solution, the variation range of its pH value is that pH=2.2-7.8(is that these two kinds of solution mix issuable pH value), such as McIlvaine at J Biol Chem, Vol.49, p.183(1921) described in.The milk sample of buffering mixes with the volume ratio of 1:1 with an amount of " McIlvaine buffer mixture ".Therefore, half of final lipides (lipid) concentration of these samples contrast that equals not cushion.As a result, the volume weight PDP of every kind of buffering sample calculating suitably is adjusted into new final lipides concentration as benchmark.Two kinds of different buffer compositions are joined in each equal portions of three kinds of whole milk's samples, with two stages of the pH of the water that shortens those samples.The effect of acid stress is, is adsorbed in some the electronegative amino acid groups in the ox casein molecule on the drop by neutralizing gradually, systematically reduces the lip-deep mean charge of fat drop.The result of this action is systematically to have reduced (with two stages) interparticle repulsive force, thereby allowed the agglomeration process of fat drop in time to accelerate.

The Stress Control that whole milk's equal portions of each batch in three batches (three different ED values) are induced by acid all, and four different point in time measurement PSD:t=0,80,160 and 240 minutes (approximately) after adding acid.(measure the accumulative total that required a few minutes cause and postpone owing to carrying out each PSD, the actual elapsed-time standards of each sample and these are worth slightly deviation.) before time sequencing begins, when not adding acid (pH ≈ 6.5), every batch is measured, to set up " contrast " PSD of himself.Then after adding sour stress (being labeled as t=0), utilize the standard buffer solution of two kinds lower Stationary pH level: pH ₁=6.1 and pH ₂=5.7, shown in time point every batch is analyzed again.Choose these values, reach gradually the caseic isoelectric point of ox (electric charge ≈ 0), pH ≈ 4.7.In all research process before at room temperature (23-26 degree centigrade) determined PSD, milk sample all refrigerates at 4-8 degree centigrade.

Fig. 5 has described when not having external damping fluid to exist, and derives from the PDP value (that is, the fat drop volume is greater than 1.8 μ m, represents with the number percent of total fatty volume) of three kinds of control samples of whole milk with respect to the variation of elapsed-time standards t.For a batch #1(" 0608 ", black circle) and batch #2(" 0612 ", closed square), PDP is to the variation diagram of time t almost identical (except the experimental point that disperses).Yet, for a batch #3(" 0615 ", solid triangle) and the figure that obtains, according to the sample of its ED value " the youngest ", with batch comparing of other " always ", show as the number percent a little more than the major diameter fat drop.This latter's behavior is interesting, but does not have certain sense, and this point can be understood at once.

Acid stress has produced wonderful result to the impact of three kinds of whole milk's samples, as at first referring to Fig. 6.Be reduced to 6.1-batch of #2(closed square at minimum stress level-pH from 6.5, PDP Fig. 6) has shown the variation along with the time, the volume of larger (that is, coalescent) fat drop firmly increases, and about 0.8% during from t=0 is increased to t ≈ 1.25% in the time of 240 minutes.These variations have reflected the remarkable and progressive variation (namely coalescent) of the fat drop in the diameter afterbody greatly of PSD.Form sharp contrast with this result, along with the variation of time (and, away from experiment " noise "), for a batch #1(black circle) and the solid triangle of batch #3() PDP that obtains keeps constant basically, be presented at stable aspect measurable variation does not occur, even in " sample of buffering " that dilute according to the volume ratio of 1:1, also be like this.Certainly it is shocking, based on the ED value of each batch of indication, people can expect owing to the reduction of pH, the oldest product (batch #1(" 0608 ")) be to show maximum instable product.Such as the impact of tartaric acid stress enough large (reduction that is energy barrier between particle is enough large), cause batch #2 to show over time unstable (droplet coalescence) of quickening, then have 4 days batch #1 early than ED, will show identical even even worse behavior.This obviously is not truth.TestDate only is the previous day of the appointment ED of batch #1, but before the ED of batch #2 5 days.Yet, based on the PDP value that in sour stress being applied to these two kinds of samples, obtains afterwards, obviously before test, to compare with the milk among batch #1, the milk quality among batch #2 obviously degenerates.This discovery has represented the behavior substantially opposite with the desired behavior of ED value that is based upon these two kinds of product appointments.

The identical behavior of these three batches of milk is reflected among Fig. 7, its shown from following stronger sample stress (be pH reduce larger, from 6.5 to 5.7) PDP that obtains is to the variation of t.In this case, with when slightly gentle pH reduces (from 6.5 to 6.1), 1.25% compare the solid triangle of batch #2() the PDP value after 240 minutes, be increased to about 1.4%.This behavior is at all not strange.In case owing to having used the specific stress factor (for example pH reduces) of given level (being Δ pH), sample shows unstable, stress level higher (being that Δ pH is larger), response is also with regard to larger (being that PDP is larger).Yet, such fact surprisingly: because this larger sour stress level, at a batch #1(black circle) behavior in still do not have observable variation.At last, and not at all not curiously, in whole 8 days, higher levels of sour stress is on the solid triangle of batch #3(of " the youngest " in three batches of milk before ED) the PDP value that obtains there is no measurable impact.

The PDP of the calculating of observing shown in Fig. 5-7 is summarized in the table 1 the time variation of every batch of milk and the dependence of sour stress level (pH).Result to the in time performed linear regression analysis of the data that change of t of the PDP of each pH value and every batch of milk also is summarized in the table 1.Batch #2(0612) every kind of sour stress (pH) level has been presented, the correlativity of almost Perfect is consistent between very high correlation coefficient r value (namely very near ideal value (r=1)) and PDP and the elapsed-time standards t.Particularly pH=6.1 and 5.7 o'clock, r be respectively 0.995 and 0.997(table 1 in bold face type).By the PDP that will observe to the least square linear fit of time t data obtain relevant with each pH value that reduces shown in slope value, provide that the inferior effective quantitative measurment of batch #2-namely how soon it go to stablize behind the sour stress factor of application.For the instable quantitative measurment that realizes inducing in sample by the stress of using specified level, may be useful with the increase (namely with respect to control sample) of slope divided by the changes delta pH of pH.The r value of batch #2 has been strengthened the in the present invention predicted value of the stress test method of the quickening of general introduction so near the consistent fact, and has approved the previous unstable or inferior conclusion that had drawn for this sample.As the quantitative discussion of front, for batch #1 or #3, for any stress level (that is, any pH value that reduces), there is not to find so strong correlativity between the PDP value of calculating and the elapsed-time standards.The regretional analysis value be that apparent-its permission is associated quantitative meaning with the experimental result of observing.

By being the results are shown among Fig. 8 for the representational PSD that the milk sample of batch #2 that applied acid (pH5.7) obtains by SPOS-LE, from this PSD PDP value the calculating chart 7 as a result.After batch #2 is applied the acid of pH=5.7, approximately through drawing large (〉 the 1.8 μ m of four kinds of diameters after 0,80,160 and 240 minute time) " afterbody " of fat drop (perhaps more correctly, " spheroid ").These afterbodys with the form of total concentration draw-be that the # population (drop) of every ml milk is with respect to particle diameter (μ m).Because coalescent gradually to the drop sour or that low pH stress causes that sample applies, they show that clearly the fat globule concentration that changes greatly along with the time increases.Those that diagram shows among these " afterbodys " result and Fig. 4 B previously discussed are similar.Fig. 9 has shown that the differential with the absolute volume mark of the corresponding fat globule of particle concentration afterbody of Fig. 8 distributes.The increase and increasing in time of the volume fraction of each liquid-drop diameter is clearly in the disperse phase.The accumulated total of all volume fractions of every kind of sample (for all particle diameters) has produced batch #2(pH=5.7 that paints among Fig. 7) each PDP value.Generally speaking, for excellent and be assumed at first rotten morning batch based on its term of validity (ED) of previous appointment, cause obvious identification to relatively inferior dairy product by applying surface charge that sour stress drop low fat drips with respect to test.In order to disclose these unexpected results, need to be to these batches stress application, because the PDP value when not having sour stress is concerning all tests three batches basic identical (Fig. 5).Therefore, macroparticle or drop will be obvious at the serviceability that the sensitive measurement of the little variation that produces aspect the volume fraction combines in this new method that increases systematically, gradually the ground stress application to emulsion/disperse phase and the disperse phase.

The second research comprises three batches of identical whole milks is exposed to the second stress factor-addings adsorbing electrolyte, allows can be adsorbed on the surface of fat drop with the ion from solution of suitable electric charge.Especially, with lime chloride (CaCl ₂) (a kind of inorganic divalent salts) join in the milk sample, causes that some are from the Ca that separates ⁺⁺Ion and drop surface conjunction.The sample of stress application adopts by comprising 0.2M(29.4g/L) calcium chloride dihydrate (CaCl ₂2H ₂O) standard stoste preparation.In order to produce the 0.005M(0.735g/L of expectation) the calcium concentration of final adding, the lime chloride stoste of 1mL is joined in the 39mL milk.Calcium concentration in final expectation is 0.010M(1.47g/L) situation under, the ratio of calcium stock solution and milk sample is doubled (being that 1mL joins among the 19mL).As a result, the volume that calculates for every kind of sample that has applied calcium stress-weight PDP is suitably adjusted to the new final lipides concentration of benchmark.Therefore, in order to increase the calcium concentration of the aqueous phase in those samples two stages, two kinds of different calcium stress concentrations are joined in each equal portions of three kinds of whole milk's samples.Identical with the sour stress factor that adopts in the first research, this second stress factor is designed to reduce the net charge on the drop, thereby reduces the height of energy barrier between drop and promote droplet coalescence.Yet in this case, the mode that reduces surface charge is different.At first, positively charged Ca ⁺⁺Ionic adsorption causes the clean minimizing of the electric charge on each particle in the drop of oppositely charged surface (by the ox casein molecule that has adsorbed pH 6.5 times electronegative).Join the CaCl in the sample ₂Concentration larger, the Ca of being combined with the coated fat drop of each casein ⁺⁺Number of ions is just more, and the mean charge that produces on the described sample is just fewer.(the Ca that this conclusion supposition adds ⁺⁺Concentration is not high to causing electric charge " counter-rotating ", thereby causes at the clean positive charge of the surface band of particle.）

Therefore, for first approximate, by adding CaCl ₂And can have and in the first research, add the identical effect of acid as stress-namely reduced the net charge on the fat drop the milk sample stress application, thereby reduced the height of energy barrier between drop.Yet, also have another factors contribute-namely because from the removable Ca of solution ⁺⁺And Cl ^-Ion is in the continuous aqueous phase diffusion of milk, and the electric double layer thickness relevant with charged particle significantly reduces (and therefore overlapping) potentially.This shielding mechanism has the effect that further reduces barrier height, and it provides the extra stable stress that goes for the fat drop that disperses.In principle, with coalescent the comparing that only occurs by the mean charge that reduces on (specified rate) drop in the situation about not existing the obvious increase of Coulomb repulsion shielding between drop, the increase of this mechanism can cause faster and stronger droplet coalescence.

The second research was carried out after sour stress studies is finished in two days.Therefore, the ED of batch #1 surpasses 1 day, and remains on front 6 days of the ED of front 3 days of the ED of batch #2 and batch #3.Each batch added two kinds of Different Ca ⁺⁺" the calcium stress " of concentration (equaling 0.005M and 0.01M).Each batch provides its " contrast "-namely, do not have the CaCl of interpolation ₂Six different time intervals are studied milk sample within 24 hours time period, and identical with the front, and all samples is at room temperature analyzed, all samples (4-8 degree centigrade) of refrigeration between analyzing.In Figure 10-13, summarized ion induction to the impact of the coalescent contrast of the stability of disperse phase and fat drop.In having summarized among Figure 10 during 24 hours, batch #1(" 0608 "), " contrast " sample (does not add CaCl ₂, black circle) and to have added concentration be the 0.005M(closed square) and the solid triangle of 0.01M() CaCl of two kinds of concentration ₂The time dependent calculated value of PDP.Adopt with Figure 10 in identical mark, Figure 11 has summarized batch #2(" 0612 ") the result, and Figure 12 has summarized batch #3(" 0615 ") the result.Figure 13 is the compressed version of Figure 11, allows batch #2, CaCl ₂0.01M(total data point set solid triangle) all is plotted.

As seeing from Figure 10 and 12 CaCl of 0.005M ₂Join in the milk, concerning the PDP value of the measurement of batch #1 and #3, do not have appreciable impact.Even in " applying the sample of calcium stress " of the dilution proportion 0.005M that is respectively by volume 1:39 and 1:19 and 0.010M equal portions, measurable variation does not occur in its stability yet.That is to say, comprise that the concentration of major diameter fat globule of the PSD afterbody of measurement does not have significant change.Obviously, the CaCl of this adding ₂Level is not enough to make significantly batch #1 and #3 go to stablize in the time frame of studying.Yet the calcium stress of this floor level makes the PDP value (except t=0) of batch #2 produce measurable increase, as shown in figure 11.Compare with a batch #1 of one day of ED who surpasses indication, batch #2 has shown its inferior characteristic under stress again, although in fact also remain 3 days before the ED of its indication.

With these results and the CaCl that works as adding ₂To compare be significant to resulting accordingly result when concentration was doubled to 0.01M.At a batch #1(Figure 10, solid triangle) situation under, the stress level of this rising has produced the PDP that significantly depends on the time to be changed, from when the t=0 just be lower than 1% to t=24 hour the time be approximately 1.5%.Although this sample before had resistance to the sour stress level that is applied to it within the time period of analyzing, batch #1 obviously is subject to the impact of this higher calcium stress level-may aging with it (namely surpassing its ED) relevant.Importantly be although should be pointed out that the aging of product, still to need the CaCl of maximum concentration ₂Stress factor makes a batch #1 go to stablize.At a batch #2(Figure 11, solid triangle) situation under, higher stress level has also produced the variation that obviously depends on t of PDP, batch #1 temporal evolution observed of having given counterevidence reaches and comprised ≈ 12 hours.Yet, surpassing this time, the PDP of measurement increases in time greatly and accelerates, and (solid triangle, the ratio of PDP have compressed 5 times) almost reached 7% after 24 hours as shown in figure 13.(also have dense tart flavour to prove at this point.) this result is basically identical with the result of batch #2 that before obtained, again set up for certain its inferior about other two kinds of samples, especially compare with a batch #1.Obviously, suppose the CaCl of PDP to adding that after surpassing 12 hours, measures ₂For becoming gradually large nonlinear response, this lime chloride stress level can not be considered to " little " of the disperse phase in batch #2 situation disturbed again.(under the concentration conditions of this situation, even previous stable batch #1 also " collapse ".) in the situation that batch #3 (Figure 12, solid triangle), within the time period of whole experience, higher stress level only makes PDP produce subtle change, this with this be the dairy product of " the youngest " and therefore (at all strange) it be that the most stable this fact is consistent.

Show among Figure 10-13 that the PDP that calculates changes and the calcium stress level the [CaCl of each batch milk to the time ₂] viewed dependence summarizes in Table I I.To each [CaCl ₂] value and the PDP of every batch of milk and the result of the linear regression analysis that the t data are carried out also be summarized in the Table II.Batch #2(0612) to every kind of calcium stress level [CaCl ₂] all demonstrated near desirable correlation coefficient r value.Particularly, [CaCl ₂] when equaling respectively 0.005M and 0.1M, the bold face type in r=0.927 and the 0.934(Table II).With each [CaCl ₂] slope value of the conduct indication that value is relevant provides the inferior useful quantitative measurement of batch #2 again.Utilize sour stress, the unsettled quantitative measurement of inducing in order to obtain in sample, applying given stress level, with the increase (namely with respect to control sample) of slope divided by the [CaCl that adds ₂] value be useful.The r value of batch #2 has quite been strengthened the predicted value of the quickening stress test method of the present invention's general introduction again near this consistent fact, and has again approved the unstable or inferior conclusion that before this sample had been drawn.As top qualitative discussion, adopting high stress level [CaCl ₂The PDP value of calculating of batch #1 and the similar but very not strong correlativity (r=0.897) between the elapsed-time standards t have been set up during]=0.01M.Comparatively speaking, simultaneously, owing to a batch #3 is the youngest in three kinds of samples and is assumed to this most stable fact, in response to a batch #3, only set up the correlativity (r=0.639) of PDP to the medium tenacity of t.Adopt the highest [CaCl ₂], the r value is important to a batch #2 not only, and also is this important fact to batch #1 and #3, shows for this calcium stress factor to have " threshold value " limit.In this level, in the milk of all batches, all induced unstablely, and do not consider they quality itself.

In the ending of the discussion of studying about the second that relates to calcium stress, adding the CaCl that produces the 0.01M of the higher level of the PDP value of the raising of demonstration among Figure 11 and 13 ₂The time, the PSD that primary inspection derives from the milk sample of inferior batch #2 also is useful.The PSD afterbody (# particle/ml and particle diameter (〉 1.8 μ m) of the variable concentrations that obtains in the elapsed-time standards of 6 measurements) is shown among Figure 14.Obvious PDP value is increased to 12 hours the gradually increase up to ≈ in time among Figure 11, can regard " details " relatively little among Figure 14 as, and its PSD afterbody is very alike each other.After 24 hours, corresponding with the very large variation of this time PDP shown in Figure 13, these great variety that change owing to the afterbody of observing become short and small.The corresponding of absolute volume mark of these 6 PSP afterbodys is shown among Figure 15.Again, the fat globule concentration of large (" separator ") that obvious batch of #2 formed between 12 to 24 hours has great increase, and other applies this and early application the factor and prove that it is that more inferior sample is consistent.The result of these calcium stress tests has shown that the calcium ion that adds is time correlation and concentration dependent on the impact of whole milk's stability, and viewed stability is lack of consistency under storage life (ED) of proving again appointment concerning batch #2 and the stress.In this case, seem when all preparations conversely with to a certain degree or another kind of degree when being affected, be applied to the level (being 0.01M) that the calcium stress in the milk sample improves higher than required level.Yet batch #2(had before proved defectiveness) to the response of the stress level that increases again obviously greater than other batch.As early discussing, compare with the situation of sour stress, be adsorbed onto the mutually coupled additional mask mechanism in drop surface with calcium ion and cause faster and stronger droplet coalescence.

The result of the stress studies of above-mentioned review has proved that obviously this new quickening stress test method detects the ability of the marked difference between the milk of three different batches of same process plants.The application of new method of the present invention has been studied different milk sample qualitative differences by two kinds of dissimilar stress factors.Every kind of stress factor all have reduce be responsible for the droplet coalescence rate is dropped to minimum, thereby guarantee the relative height V of product potential barrier between the drop of one section acceptable time period internal stability _MAXThe effect of/kT.Although every kind of stress factor reduces the mechanism difference of relative barrier height, in each case, from stability viewpoint, to compare with other batch, the milk of batch #2 all is accredited as inferior clearly.Therefore, obviously, the new method of instruction can be distinguished on basis quantitatively and qualitatively and adopt stability or qualitative difference between disperse phase that conventional existing method may not reliably identify and the emulsion here.And obviously, the term of validity of the routine of commodity appointment, or even those terms of validity of strictly setting up also may not be effective.

For general applicability and the effect of the quickening stress test new method that further specifies this disperse phase, the result who summarizes the identical research that derives from the oil-in-water emulsion that is applied to another type is useful.Disperse phase is comprised of the plant oil droplet, and is stable by anionic surfactant, is utilized to negative charge is applied to oil droplets.As described below, a kind ofly be applied to stress factor in the plant fat emulsion from obtaining its validity from the above-mentioned machine-processed different mechanism that is applied to the stress factor representative the milk research.The sample of stress application is analyzed in the mode of front, employing is based on the particle size analysis (SPOS) of delustring (being SPOS-LE), and the result (scope: percent by volume or the PDP of oil droplet 1.8-50 μ m) (" ball ") at the different time interval represents with major diameter equally.

In these researchs (three different experiments), in order to assess the variation along with the time, the ion of adding (both having comprised that absorption also comprised shielding) potpourri is on the impact of emulsion stability, with low concentration (0.05M) univalent cation (Na ⁺, K ⁺) potpourri and low concentration (0.003M) bivalent cation (Ca ⁺⁺, Mg ⁺⁺) potpourri join in the oil-in-water type plant fat emulsion of 5%w/v.After this this stable cationic stock blend that goes that uses in these experiment overall processes is known as " hybrid ionic kind ".The disperse phase of final plant fat emulsion and the ionic species of mixing adopts aforementioned manner, by assessing in the measurement of t=0 PSD of (carrying out immediately after adding the hybrid ionic kind) constantly the time.After 8,16,20,24 and 28 hours, at room temperature (23-26 ℃) measures disperse phase again.The PDP that obtains and the activity-summary of t are in Figure 16.There is measurable variation in the large diameter afterbody of PSD, shows the coalescent beginning of obvious oil droplet (occurring after about 20 hours (1200 minutes)).Thereafter the PDP value that obtains obviously shortens.Set up " contrast " test, the hybrid ionic kind that is about to low concentration joins in the vegetable oil emulsification liquid and causes it to become unstable, but only just obviously shows after about 24 hours elapsed-time standards.

In order further to assess the validity of the new method of instruction here, different stress factors systematically are applied in the vegetable oil emulsification liquid of this charge stable, whether in far faster than 20 hours, determined reliably (that is, on the basis of greatly accelerating) with the unstable feature of determining it.One of these stress factors are that control adds simple monovalent salt NaCl.With with CaCl ₂Join in the milk disperse phase differently, cause that electric charge on the fat drop is because the Ca of some addings ⁺⁺The combination of ion and reducing, NaCl joins in the disperse phase will can not cause Na ⁺The appreciable combination of ion and electronegative oil droplet.But, in this case, the Coulomb repulsion (that is, having shunk the electric double layer relevant with drop) between the major effect of the salt ion of the adding charged drop that has been partly shielding effect, thus promoted the coalescent of them.When describing between the partly shielding effect particle Coulomb repulsion with simple monovalent salt NaCl, should be appreciated that simple divalence or trivalent salt also can be used for the partly shielding effect Coulomb repulsion.

In second series experiment, datum quantity (identical with the concentration of using previously) that will " hybrid ionic kind " join the middle use of the above-mentioned experiment of just having discussed (i.e. " benchmark " disperse phase) identical vegetable oil emulsification liquid (5%w/v) four separation equal portions or batch in.Meanwhile (t ≈ 0) adopts the only mechanism of shielding of just having discussed, systematically to a batch stress application.In each sample, set up the NaCl concentration that increases gradually: batch #1=0M(" contrast ", the ionic species that benchmark mixes); Batch #2=0.05M(2.93g/L); Batch #3=0.1M(5.86g/L); Batch #4=0.15M(8.79g/L).(batch #2-4 equals the salt stress that batch #1 adding level increases.) result, the volume that calculates for every kind of sample that has applied salt stress-weight PDP is suitably adjusted to the final lipides concentration of new benchmark.Then identical with the front, assess the stability of (23-26 ℃) under the room temperature every batch by the PSD that measures, but at five different time points: t=0,60,120,180 and 240 minutes (whenabouts).This research is designed to, by approximately with the order of time span-namely from 20 hours to only 1-4 hour, systematically accelerate the coalescent beginning of obvious, measurable oil droplet.

The result of these measurements is summarized among Figure 17, is shown as the PDP value that the NaCl concentration of each time point and adding obtains: 0M(" contrast ", soft dot); 0.05M(black circle); 0.1M(closed square); 0.15M(solid triangle).Obviously, the increase of the NaCl concentration of adding causes existing in the PDP value increase of classification, quickening.The stress level that applies is higher, and significantly the coalescent beginning of oil droplet is just faster.In fact have doubling of earliest time point t ≈ 0 PDP of place at the highest stress level (NaCl that namely adds 0.15M), mean sample finish PSD measure in the needed short time-only about 5 minutes-obviously gone to stablize.Obviously, by selecting advisably stress level (namely add NaCl concentration), this sample can be used for being disclosed in than do not exist gageable stress (namely〉20 hours, interior its potential unstable degree of the time period of required time much shorter in the time of Figure 16).

Summarize the adding observed in the Table III and removed to stablize the calculating PDP of vegetable oil emulsification liquid of hybrid ionic kind (shown in Figure 17) to the dependence of elapsed-time standards and salt stress level [NaCl].The linear regression analysis result that PDP and the t data of each value of [NaCl] are carried out also is summarized in the Table III.All [NaCl] stress levels have all been obtained near desirable correlation coefficient r value.Particularly, when [NaCl]=0.05M, 0.10M and 0.15M, r be respectively 0.958,0.980 and the 0.973(Table III in bold face type).The slope value relevant with each [NaCl] value that shows provides when having the ionic species that mixes again, the useful quantitative measurement of the unstable or inferior degree of vegetable oil emulsification liquid.Identical with the front, with the increase (namely with respect to control sample) of slope divided by [NaCl] concentration that adds, to reach being useful by in sample, adding the unsettled quantitative measurement that the given applied stress level induces.All r values for whole three [NaCl] values have so been strengthened the predicted value of the quickening stress test method of the present invention's general introduction again near the consistent fact, and have approved the unstable conclusion that derives from this sample.Owing to having added the ionic species that mixes, see the discussion of Figure 16 and front, after about 20 hours, observed this vegetable oil emulsification liquid and become unstable.Systematically add significantly, the NaCl of varying number brings into play its institute can role-namely, accelerate the repeatably instable beginning of disperse phase.

In the third experiment, again the ionic species (same concentrations) that mixes is joined identical vegetable oil emulsification liquid (5%w/v) four separation equal portions or batch in, form identical " benchmark " disperse phase that uses in the experiment with the front.Meanwhile (t ≈ 0), systematically to batch applying sour stress (namely reducing pH), identical with the technology of in a kind of the stability of milk research, using previously discussed.Yet this moment is in the ratio that increases gradually hydrochloric acid (HCl) being joined batch, to reduce the pH of final disperse phase by the stage.The plant oil droplet that comprises the emulsion of beginning is stablized by the lecithin surfactant, and isoelectric point (pH) is approximately 3.2.By to this by adding acid and add stress being lower than the stable disperse phase of the anionic surfactant of inducing net negative charge under the lower sour condition, cause the electrostatic charge on the milk drop of fine dispersion to reduce, thereby induce its agglomeration.The pH of the original sample of stress application is not 6.56.With the sour stress of recruitment gradually join emulsion batch in (containing the potpourri that anion species is stablized in commonly used going), the concentration that is equivalent to HCl is approximately 0.006M(0.228g/L), 0.012M(0.456g/L) and 0.025M(0.912g/L), in these samples, produce respectively 5.65,5.13 and 4.46 pH value.Therefore electric charge on the oil droplet falls in succession.The final pH value that has applied sour stress sample that forms is: batch #1(" contrast "), and pH=6.56; Batch #2, pH=5.65; Batch #3, pH=5.13; Batch #4, pH=4.46.Identical with the experiment of front, assess each batch by measuring PSD at five different time points: t=0,60,120,180 and 240 minutes (whenabouts).Identical with the front, this research is designed to accelerate the coalescent beginning of obvious, measurable oil droplet.Calculate the every kind volume that has applied the sample of calcium stress-weight PDP is suitably adjusted to the final lipides concentration of new benchmark.

The result of these measurements is summarized among Figure 18, has shown the PDP value that the pH value for each time point and reduction obtains: pH=6.56(" contrast ", soft dot); The pH=5.65(black circle); The pH=5.13(closed square); The solid triangle of pH=4.46().The PDP that shows among Figure 18 figure is to add situation about showing among the Figure 17 that obtains the disperse phase of hybrid ionic kind similar from the vegetable oil emulsification liquid that contains that applied NaCl stress.There is the increase of classification, quickening in the PDP value along with the pH reduction of measuring.Quickening in the required time frame of the unstable degree of setting up disperse phase is similar to situation about obtaining from the disperse phase that has applied NaCl stress.The stress level that applies is higher, and significantly the coalescent beginning of oil droplet is just faster.At the highest stress level, pH=4.46 increases more than 50% in the PDP value of earliest time point t ≈ 0.Sample is measured in the required short time (about 5 minutes) and is again gone to stablize significantly finishing PSD.Identical with the front, be disclosed in than its potential unstable degree in the time period that does not have the required time much shorter of gageable stress by selecting advisably this disperse phase of stress level (in this case, causing pH to reduce owing to adding HCl).

Summarize the adding observed among the Table I V and removed to stablize the calculating PDP of vegetable oil emulsification liquid of hybrid ionic kind (being shown among Figure 18) to the dependence of elapsed-time standards and sour stress level (pH).The linear regression analysis result that PDP and the t data of each pH value are carried out also is summarized in the Table IV.Again, all sour stress (pH) levels have all been obtained near desirable correlation coefficient r value.Particularly, as pH=5.65,5.13 and 4.46 the time, r be respectively 0.972,0.987 and the 0.996(Table IV in bold face type).The slope value relevant with each pH value that shows provides the useful quantitative measurement of the unstable or inferior degree of vegetable oil emulsification liquid when having the ionic species that mixes again.Identical with the front, with the increase (namely with respect to control sample) of the slope variation (Δ pH) divided by the pH that adds, to reach being useful by in sample, adding the unsettled quantitative measurement that given applied stress (pH) level induces.For all r values of all three values of the pH that reduces so near consistent true proving again the predicted value of the quickening stress test method summarized of the present invention, and approved the unstable conclusion that draws from this sample.Systematically add the acid obviously accelerate brought into play its institute can role-namely, accelerate repeatably unsettled beginning of disperse phase.

Above-mentioned experimental verification, wherein stress factor special, strict difinition systematically is applied to the emulsion of two kinds of different charge stables, and determine " disperse phase number percent " or PDP as the function with elapsed-time standards by sensitivity and quantitative device, with the basis of three kinds of preferred embodiments forming the inventive method.Each embodiment that the following describes is centered by systematically being applied to different, specific stress factor in the interested disperse phase sample, to assess its stability on the basis of accelerating.

First embodiment of the inventive method is shown among Figure 19 with the form of chart, the stress factor " A " that utilizes the contrast that comprises pH to change ,-namely, the pH that relates to the external phase of the disperse phase discussed or emulsion raises or reduces.In this embodiment, by changing its pH the initial sample stress application is caused that the lip-deep mean charge amount of particle (or drop) reduces, and causes barrier height V between particle _MAXReduce, and cause the corresponding quickening of irreversible agglomeration (perhaps adjacent drops is coalescent) speed between the adjacent particles.Selection is that increase or the pH that reduces sample depend on that particle (or drop) entrained net charge under their normal interference-free states is positive charge or negative charge.If the pH of undisturbed disperse phase is greater than " isoelectric point " or IEP(namely, the pH value of the electric charge on the particle close to zero time), particle carries clean negative charge.In this case, stress factor comprises the pH that reduces sample with one or more predetermined increments.The titration of this system joins in the initial sample and finishes by the concentrated acid amount (form " pure " or buffering) that adds one or more measurements.Each final pH value reduction causes disperse phase more near its IEP, has correspondingly reduced the mean charge on particle or the drop, thereby has caused particle aggregation effect or coalescent tendency correspondingly to increase.

On the contrary, if the pH of initial dispersion phase is lower than IEP, the net charge that particle carries is for just.In this case, stress factor comprises by systematically adding concentrated base (being similarly form pure or buffering), increases the pH of disperse phase with one or more predetermined increments.Each pH value increase all causes disperse phase more near its IEP, finally reach with by coming to the same thing of acid being joined the disperse phase that contains electronegative particle obtains-namely, on the basis of accelerating, disperse phase " is pushed away " gradually to unstable, shown more rapidly particle aggregation effect or coalescent.

Illustrate such as diagram in Figure 19, initial dispersion phase to be measured or emulsion are divided into equal portions that the N+1 kind separates or batches 10 ₀, 10 ₁, 10 ₂... .10 _N, N 〉=1 wherein.Each equal portions contains identical sample volume, perhaps, may contain different sample volumes, and this depends on the particular design of stability test.Be known as 10 ₀The sample equal portions consist of " contrast " of stability test because it is not applied any stress (acid or alkali).It is not strict necessary comprising this control sample in testing scheme.Yet the assumes samples composition has a production phase to recurrent changeableness of another production phase, usually is desirably in to comprise the not sample of stress application in the testing procedure.Like this, the ability that new quickening stress test method detects the subtle change of particle aggregation effect has reliably strengthened potentially, and has shown the quality of each batch.

After this beginning at the stress test of accelerating is called t=0,11 ₁In time, join acid or the alkali of specified quantitative in the N=1 sample equal portions.In the situation that sour stress is fit to, the pH of disperse phase thereby from its initial value (that is, the value of control sample) pH ₀Reduced given (be generally predetermined amount, but must) increment Delta pH ₁, must the value of making new advances pH ₁=pH ₀-Δ pH ₁This new lower value is measured with idealizing, but can calculate (based on the volume of sample equal portions and for affecting concentrated acid that pH reduces or pH and the volume of damping fluid) out after adding stress factor.Alternatively, because the impact of the alkali that adds increases increment Delta pH at the pH of initial dispersion phase ₁Situation under, the pH of the disperse phase of generation can be expressed as pH ₁=pH ₀+ Δ pH ₁

Shown in Figure 19 diagram, will comprise that the stress factor " A " that adds acid or alkali (any all suitable) is applied to different (can differentiate ideally) equal portions 11 of N kind of disperse phase to be measured ₁, 11 ₂... .11 _NIn some cases, the disperse phase of discussing can have goodish feature to be described and/or predictability (for example, during the routine monitoring of the production run good to behavior), to such an extent as to only need to apply the stress of single level-namely, ± Δ pH ₁, to determine its stability, perhaps deficient in stability.In these cases, N=1 is just enough.Yet, when to new product or when improving product and assessing, shown in various examples described herein, in order to obtain a series of independently PDP results, at least should be with two (namely, N 〉=2) the increase stress of level be applied to initial dispersion mutually in, may obtain larger accuracy and reliability.In the situation that minimum, the application of extra stress increment-namely, ± Δ pH _I, wherein I=1,2 ... N ,-can produce the larger reliability that final PDP measures, thereby obtained the larger confidence level about the sample stability conclusion.Usually, if the stress factor " A " of N kind varying level is applied in the disperse phase, the pH value that generation N kind has applied stress sample equal portions can be described as: in the situation that apply sour stress, pH _I=pH ₀-Δ pH _I, perhaps in the situation that apply alkali stress, pH _I=pH ₀+ Δ pH _I, wherein I=1,2 ... N, and Δ pH ₁＜Δ pH ₂＜...＜Δ pH _N

After different acid or alkali stress add the initial sample equal portions with the N kind, the particle size distribution of each equal portions (PSD) and the contrast of stress application (#0) sample not adopt the particle size analysis technology with enough sensitivity and resolution to measure when 12 step.For the top reason of having discussed, preferably typically based on delustring (LE) principle, but also optionally based on the principle of light scattering (LS), perhaps the two is in conjunction with the SPOS technology of (" LE+LS "), and this depends on the type of emulsion or disperse phase to be assessed.In this case, the PSD that records typically relates to the scope of particle diameter, d 〉=d ₀, it has defined " afterbody " of the maximum particle that comprises PSD.Based on the maximum analysis time of expectation and the degree of Sample Dilution, threshold value d ₀Be chosen as statistical significance (namely believing/the make an uproar ratio) maximization with final PSD.Typically, (that is, fast as far as possible) carried out in the PSD measurement that is used for each sample equal portions immediately after applying acid or alkali stress factor.Yet in some cases, may be desirably in stress factor is applied to after the specific sample, before beginning to measure PSD, wait for the time of one section length-specific.Based on the complicacy of the device that is used for the execution stress test, can follow equally continuous coverage PSD of another sample by sample equal portions, perhaps parallel measurement almost adopts simultaneously a plurality of independently sensors and pertinent instruments to carry out each SPOS and measures.

At the PSD(d 〉=d that measures each sample equal portions ₀) afterwards, immediately by each PSD that records calculating and elapsed-time standards and stress level (Δ pH when 13 step ₁) " disperse phase number percent " or the PDP(of each sample also are d 〉=d usually accordingly ₀).After this step, when 14 step, allow each sample time of origin to postpone Δ t, then again measure PSD, and calculate the corresponding PDP value of each sample.Time delay Δ t typically is chosen as all samples basic identical, but this is not necessary.Randomly, based on the acid of selecting or the level of alkali stress, it can be selected as one or more samples different.Alternatively, based on being carried out PSD, the sample equal portions of whole series measure the required time, and the characteristic time that applies the particle aggregation effect of the quickening that different stress levels produce, the nominal time between the continuous series that PSD measures postpones may be selected to be zero.Under latter event, the PSD of series of samples equal portions measures and the calculating of PDP value has become continuous process effectively, and does not have the obvious pause stage between the continuous series of measuring.

The repetitive cycling that a series of PSD that applied the sample equal portions (comprising the not control sample of stress application) of acid or alkali stress measure and corresponding PDP calculates is carried out the sufficiently long time, so that to every kind of stress level that applies, allow the reliable PDP that determines as the elapsed-time standards function.Suppose that the stress level that applies is chosen advisably, thereby (be maximum Δ pH for the highest at least stress level _I), after the relatively short time period of expectation, can be observed the remarkable increase of PDP value.The number of times of measurements and calculations circulations is normally predetermined, has particularly described well in the past in the situation about the feature of the stability of disperse phase and performance.Alternatively, for about stability with quality is relatively new and the disperse phase of " the unknown ", measure circulation number of times and thereby whole duration of the stress test of quickening can be " indefinite ".In this case, only the PDP value variation that applies one or more stress levels (acid or alkali) is reliably being determined with permission through ending this process after the sufficiently long time.If after the time period of reasonable length, even under the high stress level of stress application, also do not observe the meaningful variation of PDP value, usually adopt a series of new more high stress level Δ pH _IRepeat this process.

By above-described process, a series of PDP value (d 〉=d have been obtained ₀) as the function of pH and time t.By these PDP values, can when 15 step, draw at least two kinds of amounts that come in handy or a series of amount.In this tittle first is for each given pH value, and PDP is with the rate of change of elapsed-time standards t,

Calculated respectively the horizontal pH of each stress application (acid or alkali) _I, i.e. pH ₁, pH ₂... Ph _NThese local derviation numerical value.In Table I, show to be used for three kinds of whole milk samples, and show in Table IV that the linear regression analysis by the PDP of each pH value and t that is used for vegetable oil emulsification liquid discussed above obtains be somebody's turn to do " slope " value.In the situation that milk sample is applied sour stress, at pH ₁=6.1(Fig. 6) and pH ₂=5.7(Fig. 7) time, in the situation that sample " 0608 " and " 0615 ", along with the increase of time, PDP remains unchanged substantially, and perhaps in the situation that sample " 0612 ", it is linear increasing in time." slope " Δ (PDP) that is obtained by linear regression analysis/Δ t is at pH ₁=6.1 o'clock is 0.00204, and at pH ₂=5.7 o'clock is 0.000260.

The above has also discussed, in the situation that there is an amount of curvature measure (Figure 18) of observing among the PDP that reduces the pH value with relevant some of the sour stress that applies and the t figure in vegetable oil emulsification liquid (adding the ionic species of mixing).In the sort of situation,

Value not only depends on pH value (that is, increasing along with the latter's reduction), and depends on the t value in suitable degree.Under any circumstance, for the pH value of all employings, the curvature of PDP and t is small enough to allow linear-apporximation, can be by each pH to allow slope Δ (PDP)/Δ t _IThe single value of value characterizes.Shown in Table I V, when pH was reduced to respectively 5.13 to 4.46 from 5.65, slope value increased gradually, and from 0.00037 to 0.00072 to 0.00099.(when pH=6.56, the slope 0.00003 of control sample is ignored.）

Exist another kind of can from a series of PDP values derive amount-for given elapsed-time standards t, the PDP increase that per unit pH changes is designated as

This local derviation numerical value can calculate the added value (if necessary, inserting to obtain the PDP value of each expectation t value between the actual experiment number of times) of various elapsed-time standards.For given t value

Value depends on pH-namely usually, and PDP is linear the increasing along with the increase (or minimizing) of pH not necessarily.Yet, the variation (being Δ pH) along with stress level is described and the PDP that changes is very easily with linear-apporximation, the Δ (PDP) of " slope " available each t value/Δ (pH) is similar in this case.Certainly, suppose

Slope for just, this slope increases along with the increase of time t usually.For example, in the situation that produces data from applied sour milk batch 0612 (Table I), dropping to 6.1((with pH from 6.6 is Δ pH=-0.5)) it is relevant that slope Δ (PDP)/Δ (pH) increases as follows in time: 0.07(80 minute), 0.48(160 minute) and 0.85(240 minute).Dropping to 5.7(based on pH from 6.6 is Δ pH=-0.9) the slope value of corresponding calculating be 0.17(80 minute), 0.41(160 minute) and 0.62(240 minute).In the situation that has applied sour vegetable oil emulsification liquid (Table IV), drop to 5.65(Δ pH=-0.91 with pH from 6.56) it is relevant that slope Δ (PDP)/(pH) is as follows for Δ :-0.001(60 minute), 0.040(120 minute), 0.058(180 minute) and 0.087(240 minute).Drop to 5.13(Δ pH=-1.43 based on pH from 6.56) corresponding slope value be 0.028(60 minute), 0.064(120 minute), 0.089(180 minute) and 0.134(240 minute).At last, be 0.046(60 minute based on pH from 6.56 slope value that drop to 4.46(Δ pH=-2.1), 0.076(120 minute), 0.112(180 minute) and 0.135(240 minute).Therefore, for this disperse phase, increase with Δ pH for all elapsed-time standards value slope Δs (PDP)/Δ (pH).

In a word, the discussion of the first embodiment has kept the appointment to " figure of merit " of research disperse phase at 16 step places, but so that its stability quantitative description, and can compare together with other example or the other products of identical disperse phase.Perhaps define the simplest of the figure of merit of sample or FM and direct mode is to use Calculated value.For the horizontal Δ pH of given applied stress, stable disperse phase will produce less

Value, and inferior disperse phase will produce relatively large this parameter value.Changed specified rate Δ pH at the pH of disperse phase _IAfter obtain

Value has been described because how irreversible agglomeration occurs the variation disperse phase of pH rapidly.Thereby, based on this value, can carry out " classification " to the stability of initial sample before applying acid or alkali stress.For given pH _IIncrement (be Δ pH _I),

Be worth greatlyr, initial sample is just more unstable.

Alternatively, the sensitivity that the PDP value changes pH after given elapsed-time standards can be used for assessing the stability of initial sample.That is to say, FM can adopt and calculate in given elapsed-time standards t value (suppose the instability that this time is long enough to allow to accelerate judge itself)

Value defines.For given elapsed-time standards t value,

Be worth larger, and the stress value Δ pH that applies _ILess, initial sample is just more unstable.Disperse phase can be used for determining the optimum stress level to the sensitivity of the given variation of pH, and perhaps stress level scope is to carry out the stress test of accelerating.

Generally speaking, there are at least two kinds of simple methods to define the figure of merit of interested disperse phase.They are: 1) for the horizontal Δ pH of given applied stress _I, measure PDP with respect to the variation of elapsed-time standards; And 2) for given elapsed-time standards t, measure PDP with respect to the variation of pH.Although the value that obtains can be considered respectively, also can with them in conjunction with (linear or non-linear), form the 3rd value that derives from the above two simultaneously.In these calculating or the derivation value one or the other can usefully be compared with " benchmark " value of " benchmark " value (the successful example of the identical product that draws previously) or other comparable product.This relatively providing is used for determining whether the product of discussing enough is stabilized to allows its to continue the method for producing and selling and using, and perhaps whether the critical aspects of production run (quality that comprises original input raw material) needs the method improving or change.Be to use separately or use (that is, being contained in the suitable algorithm) as whole series of values, provide as disperse phase and specified one or more FM tolerance and so assess its stable method.

Second embodiment of the inventive method that diagram is summarized among Figure 20, all the other are all identical with the first embodiment except a bit.Unique difference is that it has utilized different stress factors, this stress factor is labeled as " B ", comprise contrast, the specific electrolytical situation of the adding of system, this specific electrolyte is providing from Xie Houneng by the ion of the charged particle in interested disperse phase or the emulsion (part) absorption.Charged ion is caused their lip-deep mean charges to reduce by the particle of oppositely charged or drop absorption.The electrolyte concentration that adds is larger, and the par that is adsorbed to the charged ion on the powered surfaces of particle or drop is just larger, and the net charge that produces at this particle or drop is just lower.In this mode to the net effect of disperse phase stress application with as the reduction of passing through pH that in the first embodiment, provides or raise effect that its stress application is reached identical.Be used for realizing that mechanism that this electric charge reduces is substantially different in each of this two embodiment, but with regard to qualitative, net effect is identical.As the first embodiment, the minimizing of this electric charge causes barrier height V between particle _MAXReduce, and cause that therefore the irreversible agglomeration speed of adjacent particles/drop is accelerated in disperse phase or the emulsion.Should be pointed out that adsorbing electrolyte joined and also it is had the second in the disperse phase of interested charge stable and go stable impact.Motion ion (positively charged and electronegative) is introduced the electrostatic repulsion forces that causes in the external phase of disperse phase between the adjacent particles by partly shielding effect the most at last.This action causes the reduction of barrier height between particle, is independent of the caused reduction of minimizing by electric charge on the particle that causes by adion.This shielding effect is the problem of the 3rd embodiment that will be discussed below.

When the second embodiment of the quickening stress test of implementing interested disperse phase or emulsion, must make two kinds of selections.The first, must select suitable electrolyte-namely, this electrolyte is after solution, can provide by with the very big ion of degree absorption in the surface of the particle/drop of opposite charges.In the situation that milk sample is carried out stress test, and as discussed above, prove that lime chloride is electrolytical a kind of fine selection, because from the Ca that separates ⁺⁺Ion obviously has the affinity to the coated fat drop of (ox) casein of the disperse phase that comprises whole milk.Typically, many electrolyte all are the appropriate candidates (supposing that ion is to a certain degree to be adsorbed onto charged particle/drop) for interested stress dispersion phase.Certainly, in case selected electrolyte, the selection that the second must be made is to add this electrolytical suitable concn scope.Can consider to estimate based on theory (that is, adopt selectivity ionic adsorption model, be combined with the numerical forecasting of dlvo theory).Alternatively, and more typically, the scope that is fit to concentration can be determined by try and error method by the stress test of interested disperse phase.

As shown in Figure 20, in the second embodiment, also adopt with the first embodiment in the same steps as used, sampling batch or equal portions 20 ₀, 20 ₁, 20 ₂... .20 _NUnique difference is, 21 ₁, 21 ₂... .21 _NThe place is applied to the essence of stress factor of N the different equal portions of initial sample.The stostes of in the time of " beginning " in the t=0(nominal) selected electrolytical difference being measured (, have given concentration) join in each equal portions of initial sample, thereby at each sample equal portions [electrolyte] ₁, [electrolyte] ₂... [electrolyte] _NMiddlely set up adion (with their gegenion) concentration different, expectation.(also set up control sample #0, wherein do not added electrolyte) after in stress factor being added N sample equal portions, identical among a series of processes that comprise the circulation of each stress test and above-mentioned the first embodiment.They are (for each sample equal portions, comprising control sample): 1) adopt suitable particle size analysis technology, preferred SPOS-LE measures PSD(d 〉=d at 22 step places ₀); 2) calculating PDP(at 23 step places also is d 〉=d usually ₀); 3) randomly, measure and before the PDP computation cycles begins at next PSD, 24 step places permission elapsed time Δ t(usually but not necessary, all identical to each equal portions in fact).

With identical among the first embodiment, for stress application (that is, the electrolyte of the various concentration of adding [electrolyte] of N kind varying level _I) and a series of PDP values of obtaining of various elapsed-time standards, produce and describe disperse phase to the increase of the amount of the sensitivity of the stress factor that applies.This tittle can be used for assessing the stability of interested disperse phase or emulsion.In 25 these tittles of step place first is that PDP is designated as with the rate of change of elapsed-time standards t under the given concentration that adds electrolyte [electrolyte]

To applying adsorbing electrolyte [electrolyte] _IEvery kind of level of stress is namely for [electrolyte] ₁, [electrolyte] ₂[electrolyte] _NCalculate respectively this local derviation numerical value.For three kinds of whole milk samples discussed above, by each [CaCl ₂] this " slope " value of obtaining of the PDP of value and the linear regression analysis of t data is shown in the Table II.Along with the increase of time, sample " 0608 " and " 0615 " are at minimum stress level [CaCl ₂During]=0.005M, it is constant that PDP keeps substantially.For sample " 0612 ", [CaCl ₂All in time linear increases (seeing Figure 11) of PDP when]=0.005M and 0.01M.The slope Δ (PDP) that obtains by linear regression analysis/Δ t is at [CaCl ₂Be 0.00023 during]=0.005M, and at [CaCl ₂Be 0.00038 during]=0.01M.For sample " 0608 ", at high stress level [CaCl ₂During]=0.01M, its PDP is substantially in time linear increase also, and slope is 0.00043.

Another amount that can derive from a series of PDP values in addition-for the PDP increase that the per unit electrolyte concentration [electrolyte] of given elapsed-time standards t value increases, be designated as

This value be used for to be calculated the value (if suitable and need, inserting) of each elapsed-time standards and will usually be depended on [electrolyte]-namely between experiment number, PDP not necessarily increases and linear increasing with [electrolyte].Yet describing with linear-apporximation that PDP changes along with the variation (i.e. [electrolyte]) of stress level is very easily, and the Δ (PDP) of " slope " available each t value/Δ [electrolyte] is approximate in this case.Certainly, suppose

Slope for just, this slope increases along with the increase of time t usually.For example, in the situation of the milk that has applied lime chloride stress batch 0612 (Table II), with [CaCl ₂The relevant Δ (PDP) in]=0.005/Δ [electrolyte] slope can calculate and increases in time by obtainable data: 40(80 minute), 19(160 minute), 23(240 minute) and 55(660 minute).With [CaCl ₂The relevant slope respective calculated of]=0.01M is: 44(80 minute), 43(160 minute), 42(240 minute) and 64(660 minute).

Identical such as the first embodiment, the calculated value that the part relevant with the adsorbing electrolyte stress that uses in a second embodiment derives-namely

With

-can be used for setting up at 26 places the figure of merit of interested disperse phase.If quantitative

Be used for defining FM, clearly, for given applied stress level [electrolyte], stable disperse phase will produce this parameter value of less, and disperse phase inferior will produce relatively large value.Alternatively, for given elapsed-time standards t value, FM can adopt

Calculated value define.Using in these derivation amounts which, is to use separately or be bonded to each other (by suitable algorithm) uses, and this all depends on the type (and concentration range) of the electrolyte stress factor of the disperse phase of research and employing.In the situation that lime chloride stress is applied in the milk sample discussed above, at [CaCl ₂PDP(Figure 10 of sample during]=0.005M " 0608 ") change in time hardly, but at [CaCl ₂Shown during]=0.01M that appropriate linearity increases.Be accredited as PDP(Figure 11 and 13 of the sample " 0612 " of substandard products), at [CaCl ₂Shown time dependent a small amount of increase during]=0.005M, and at [CaCl ₂Shown time dependent large non-linear and quick increase during]=0.01M.Finally, PDP(Figure 12 of the most stable the youngest sample " 0615 "), at [CaCl ₂Show as sample " 0608 " during]=0.005M, basically do not change with elapsed-time standards.Yet, or even at [CaCl ₂During]=0.01M, PDP has only shown less variation in time (that is, far less than the viewed variation of sample " 0608 ").Obviously, use absorption Ca ⁺⁺As the stress factor of three batches of milk, allow their by effectively and clearly " classification ".Minimus sample " 0615 " is the most stable (undoubtedly, considering its ED); Yet the oldest sample " 0608 " is second the most stable, and the sample of intermediate ages " 0612 " is shown as stability well below sample " 0608 " (it is surprised that this point is made us, and considers their ED).

On the one hand, be assumed to the electrolyte of realizing the second embodiment and selecting do not produce too strong can be by the ion that charged particle/the drop surface is adsorbed.In addition, the electrolyte concentration scope of adding may be too little, causes the net charge on the particle not change to maximum (being in maximum [electrolyte]) from very little (being in minimum [electrolyte]).This disperse phase can make it be difficult to reach PDP to electrolyte concentration variation, elapsed-time standards or linear response that the two all comprises in response to the compression of the stress factor that adds.

The of the present invention the 3rd and last embodiment similar to the second embodiment, and be illustrated and be summarized among Figure 21.Similar to the second embodiment, it also utilizes the electrolyte (yet, only refer to now " salt ") of adding to be the initial sample stress application.Unique difference is, in the situation that employing salt (being labeled as stress factor " C "), described salt is assumed that it is a kind of charged particle of firm disperse phase almost can not be included dispersion liquid from the solution generation or the charged ion type of drop absorption.But, remain in the external phase of disperse phase from the salt ion of separating, therein free diffusing.Therefore, in the present embodiment, this salt that the mean charge amount on particle or the drop of being retained in is not added into the difference amount in the initial sample equal portions substantially changes.Therefore, adding salt, to reduce the mode of stability (that is, promoting agglomeration) of disperse phase different from the mode that reaches in the first and second embodiment, in rear both embodiment, by reducing the net charge of particle surface reservation, make that repulsive force weakens between particle.But, in this case between particle repulsive force by will be movably ion join in the external phase and reduce.These ions are according to thermodynamic equilibrium, with they as " shielding " or part neutralize the electrostatic field that each charged particle sends mode and distribute.As the result of the shielding ion of these addings, repel potential energy V between particle _R(x) along with the increase apart from x between the adjacent particles decays very soon.(seeing Fig. 1-3).That is to say, characterize the K reciprocal of the Debye-H ü ckel shielding length of electric double layer thickness ^-1Reduce.The net result that this repulsion electrostatic field shielding increases is barrier height V between particle _MAXReduce barrier height V between this particle _MAXBe used for disperse phase is gone to stablize.

Equally, when implementing the 3rd embodiment, must make two kinds of selections.The first, must select that suitable salt-namely, this salt can provide the ion of the aqueous phase of the disperse phase that remaines in research after solution, can not be adsorbed onto to a great extent on the surface with the particle/drop of opposite charges.(validity that reduces the electric double layer thickness relevant with each charged particle is equally highly depended on the quantivalency of ion from the salt ion of separating, as Debye-H ü ckel theory is instructed.) vegetable oil emulsification liquid discussed above (adding the ionic species of mixing) is being carried out in the situation of stress test, sodium chloride is proved to be a kind of fine selection for the salt that adds.The second selection relates to the suitable concn scope of the salt of adding.Equally, can estimate with dlvo theory.Yet typically suitable concentration range can by the stress test of interested disperse phase, be determined by try and error method.

As shown in Figure 21, in the 3rd embodiment, also utilize with first and second embodiment in the same steps as used.Control batch 30 is provided ₀And the N kind other batches 30 ₁, 30 ₂... .30 _NUnique difference is, 31 ₁, 31 ₂... .31 _NThe place is applied to the characteristic of stress factor of N the different equal portions of initial sample." beginning " in the t=0(nominal) time stoste of the difference amount of selected salt (, have given concentration) is joined in each equal portions of initial sample, thereby in each sample equal portions, set up the different shielding ion concentrations that need.The ultimate density that adds salt is known as [salt] ₁, [salt] ₂... [salt] _N(do not add salt in the control sample) after in stress factor being applied to N sample equal portions, identical among a series of processes that comprise the circulation of each stress test and the above-mentioned the first two embodiment.They are (for each sample equal portions, comprising contrast): 1) use suitable particle size analysis technology, preferred SPOS-LE measures PSD(d 〉=d at 32 step places ₀); 2) calculating PDP(at 33 step places also is d 〉=d usually ₀); 3) randomly, next PSD measure and the PDP computation cycles before, permission when 34 step elapsed-time standards Δ t(typically, but not necessarily, basically all identical to each equal portions).

With identical among the first two embodiment, for the stress application (salt [salt] of the various concentration that namely add of N kind varying level _I) and a series of PDP values of obtaining of various elapsed-time standards, produce at 35 step places and to describe disperse phase to the amount increase of the calculating of the stress factor sensitivity that applies.That is to say, this tittle can be used for assessing the stability of interested disperse phase or emulsion.In this tittle first is that PDP is designated as with the rate of change of elapsed-time standards t for the given concentration [salt] that adds salt To each salt stress level [salt] that applies _IThat is, [salt] ₁, [salt] ₂[salt] _NCalculate respectively this local derviation numerical value.For vegetable oil emulsification liquid discussed above, this " slope " value that is obtained by the linear regression analysis for the PDP of each [NaCl] value and t data is shown in the Table III.From the PDP of some [NaCl] value and t figure, observe, have the curvature value (Figure 17) of appropriate amount.In this case,

Value not only depends on [NaCl] value (namely increasing along with the latter's increase), but also suitably depends on to degree the t value.Under any circumstance, for [NaCl] value of all employings, the flexibility of PDP and t is small enough to allow linear-apporximation, characterizes with the single value that allows available each [NaCl] value of slope (Δ (PDP)/Δ t).As shown in the Table III, when [NaCl] was increased to 0.15M again to 0.2M from 0.1M, slope value increased gradually, is increased to 0.00152 again to 0.00195 from 0.00085 respectively.(slope of control sample is 0.000098, can ignore.）

Another that can derive from a series of PDP values in addition quantitatively-for given elapsed-time standards value, the PDP that per unit [salt] increases increases,

Calculate the value of this amount for the value (if necessary, between experiment number, inserting) of each elapsed-time standards.Under given t value

Value will depend on [salt]-namely usually, and PDP not necessarily increases and linear increasing with [salt].Yet describing the PDP that changes along with the variation of stress level (i.e. [salt]) with linear-apporximation is very easily, and the Δ (PDP) of " slope " available each t value/Δ [salt] comes approximate in this case.Certainly, suppose

Slope for just, this slope increases along with the increase of time t usually.For example, in the situation of the vegetable oil emulsification liquid discussed above (adding the ionic species of mixing) that has applied sodium chloride stress, the slope Δ (PDP) relevant with [NaCl]=0.1M/Δ [salt] can calculate and increases in time by the data that provide in the Table III, and is as follows: 0.55(60 minute), 0.97(120 minute), 1.63(180 minute) and 2.30(240 minute).The corresponding slope calculated value relevant with [NaCl]=0.15M is: 0.49(60 minute), 1.16(120 minute), 1.92(180 minute) and 2.59(240 minute).At last, the slope value relevant with [NaCl]=0.2M is: 0.85(60 minute), 1.30(120 minute), 2.33(180 minute) and 2.81(240 minute).Therefore, for this emulsion, for all elapsed-time standards values, Δ (PDP)/Δ [NaCl] all increases with the increase of [NaCl].

Such as the embodiment of front, the partial derivative calculated value relevant with the salt shielding stress that in the 3rd embodiment, uses-namely

With

-can be used for setting up at 36 step places the figure of merit of interested disperse phase.If amount

Be used for defining FM, clearly, for given applied stress level [salt], stable disperse phase will produce this parameter value of less, and disperse phase inferior will produce relatively large value.Alternatively, for given elapsed-time standards t value, FM can use

Calculated value define.Using which the derivation amount in these derivation amounts, is to use separately or combination with one another is used (by suitable algorithm), and these all depend on the type (and concentration range) of the salt stress factor of the disperse phase of research and employing.In the situation that sodium chloride stress is applied to vegetable oil emulsification liquid (the ionic species potpourri of adding up stable), such as previous discussion, for all the three kinds stress factor level [NaCl] that applies=0.05M, 0.10M and 0.15M, find in time slightly non-linear increase (Figure 17) of PDP.In whole three kinds of situations, owing to having added sodium chloride, emulsion is significantly accelerated towards the obvious differentiation of unstable (being obvious droplet coalescence).[NaCl] is larger for stress level, and the degree absolute of droplet coalescence or PDP value are just larger, and PDP over time rate or Just higher.

Example such as one or more above-described embodiment are used for the enforcement that the disperse phase sample is accelerated one or more methods of stress test, usually need to use specialized equipment.The simplified block diagram of the exemplary device of any embodiment is shown among Figure 22 among a kind of three kinds of embodiment that are suitable for realizing showing among Figure 19-21.Computer-controlled automatic sampling device 38 allows a plurality of batches to interested sample dispersion phase (having suitable predetermined concentration) to carry out stress test easily.Automatic sampling device 38 diagrams are shown as the support component 39 that comprises a control, as directed can reaching up and down is displaced sideways, so that its energy movement pipeline 56 and 66, described pipeline will explain below, and it optionally is fed to sample dispersion phase or emulsion and stress factor in the test container 40,41,42 and 43; And movement pipeline 72, be used for the potpourri of sample and stress factor is optionally extracted out from test container.In the example that Figure 22 shows, the sample dispersion of four different batches in the container 40,41,42 and 43 of the proper volume of being contained in is arranged mutually.Three batches (being appointed as #1, #2 and #3) are exposed to the stress factor (being acid or alkali, adsorbing electrolyte or shielding salt) of special selection, and each batch is designated as the different stress level (namely being respectively Δ pH or [electrolyte] or [salt] concentration) of reception.The other a collection of sample (being appointed as #0) that does not have stress application factor sample in contrast, as previously mentioned.

Two kinds independently the liquid subsystem be shown among Figure 22.The first liquid subsystem 50(upper right corner) for example adopt liquid metering device 52(, syringe pump) come by pipeline 56 the initial sample disperse phase of the debita spissitudo of predetermined from keeping container 54 to be delivered to the suitable sample batch container 40,41,42 or 43 that is positioned at automatic sampling device.This liquid metering device is typically controlled by control automatic sampling device and the same computer control/processor subsystem 100 of other subsystem that comprises the proving installation that diagram shows among Figure 22.The second liquid subsystem 60(upper left corner) adopt independently liquid metering device 62(for example, another syringe pump), from container 64, to send the liquid of the predetermined that comprises selected stress factor by pipeline 66.As previously discussed, described liquid can be to have specific volumetric molar concentration with pH(or have specific composition and the specific damping fluid of pH) relative concentrated acid or alkali, or relatively concentrated electrolyte or salt, or their combination.The every kind of liquid metering device that shows among Figure 22 is controlled for control and with the same computer control/processor subsystem 100 of other subsystem communication that comprises stress test device by same.Typically, the volume of the initial sample disperse phase liquid of expectation at first is assigned in each sample batch container that is included in the automatic sampling device.The capacity distribution (being #1, #2 and the #3 among Figure 22) in each sample batch container of (typically, volume is very little) " stress factor " liquid of then expecting.The volume that joins the stress factor liquid in each container is different, is determined by specific sample batch needed final pH or electrolyte/salinity (that is, stress level).The stirring apparatus (not shown), such as mechanical agitating vane, perhaps preferred magnetic pumping stirring rod during distribution is used for the abundant mixing of the stress factor liquid of each container initial sample disperse phase liquid of realization and adding, thereby guarantees in each container it is unit for uniform suspension.When stress factor liquid is assigned to this batch, set up the demarcation start time (being t=0) of the quickening stress test of each sample batch, and should the time by 100 records of system-computed machine controller/processor.

Through (Figure 19-21) after the suitable schedule time Δ t, with applying of scheduled volume the sample dispersion phase liquid of stress from the sample batch container of expectation, shift out, and by being used for obtaining PSD(d d ₀) particle size analysis instrument subsystem 80 extract, as previously mentioned.Particle size analysis instrument 80 is single-particle optical sensor (SPOS), and comprises a laser diode 82, and it projects light beam 83 on the photodetector 88 by beam-shaping optical element 84 and light flow cell (optical flow cell) 86.Particle size analysis instrument 80, can adopt light scattering (LS) type or use the design of LE+LS combined sensor for some application although as explained above preferably according to delustring (LE) operate.Under any circumstance, analyser provides particle size distribution (PSD).Usually the suitable pumping unit 70(that is positioned particle size analysis instrument 80 " downstream " side is the 3rd syringe pump for example) the sample dispersion phase liquid that has applied stress that is used for expecting moves on to discharging 74 by pipeline 72 from a sample batch container.The disperse phase that has applied stress that these are to be analyzed extracts by light flow cell 86 with the regulation flow velocity.Flow through this light flow cell total liquid volume by the volume that obtains at first in the sample batch container (and the expection of discrete analysis sum, separate by total elapsed-time standards of test) and finally the desired statistical accuracy of PSD determine.Appropriate size by SPOS type particle size analysis instrument 80 (be d〉d ₀) the signal that produces of particle after the suitable adjusting of Signal Conditioning Equipment 90, use proper circuit in computer control/processor 100 to analyze (typically, but not necessarily identical with the computing machine that is used for other subsystem of control).As a result, draw PSD, this PSD has disclosed about the information of particle aggregation active state (for example, those comprise the macroparticle " afterbody " of PSD).

After for the first time stress factor being assigned in each sample batch container, make equally the scheduled volume of each sample that has applied stress batch add (choosing wantonly) not sample batch of stress application, with predetermined time interval one next by particle size analysis instrument subsystem 80.By each batch being adopted different particle size analysis instrument subsystems 80, each sample of scheduled volume batch can be by corresponding particle size analysis instrument subsystem parallel providing simultaneously.As a result, obtain the PSD of each sample that has applied stress batch at each elapsed-time standards value t of each batch.By each PSD, can by system computer further calculate the PDP value (that is, for d〉d ₀), and the PDP value of final calculating suitably proofreaied and correct the different volumes of the stress factor liquid that adds with reflection.Thereby, consisted of " raw data " of the quickening stress test of interested sample dispersion phase for each a series of PDP and t result who has applied the sample batch acquisition of stress, as early describing.By this a series of PDP value, obtain other interested derivative amount with computing machine, be used for characterizing stability and/or the quality of disperse phase, as mentioned above.For any given elapsed-time standards value t, described this a series of PDP value comprises PDP self, and the amount relevant with PDP, includes but not limited to: partial derivative

With

Such as the early discussion relevant with three embodiment of this method.

Although 38 diagrams of automatic sampling instrument have shown the pipeline 56 that comes self-pumping 52 and the pipeline 66 that comes self-pumping 62 and the initial sample or the stress factor that distribute can have been transferred in the selected container 40,41,42 or 43, and pipeline 72 shifts out discharge liquid by pump 70 from selected container 40,41,42 or 43, but should be understood that, as needs, other device for example computer-controlled valve system can be used for managing the movement of liquid.

As early discussing, the stress test that uses method of the present invention to accelerate interested disperse phase, and need not be by the use of SPOS technology.On the contrary, the technology of other particle size analysis also can be used for having obtained to apply the PSD of the sample batch of stress, perhaps characterizes described PSD.Therefore, replace the SPOS type particle size analysis instrument subsystem 80 show in Figure 22, the particle size detecting device that people can other type replaces.Those that mention above some adoptable technology that come in handy comprise: resistance hole, dynamics light scattering, laser diffraction (that is, Mi e scattering and/or Fraunhofer diffraction), ultrasonic attenuation and other technology.Yet, should also be understood that and in relevant apparatus, do not adopt particle size analysis instrument itself, also may realize the quickening stress test method that the present invention instructs.Above-mentioned example comprises turbidity (that is, light is by the mutually decay of the given path length of part of sample dispersion) and light scattering technique.In each case, at given elapsed-time standards interval t, can produce single digital quantity or value (being called " X " here) mutually for the given sample dispersion that has applied stress.In these measuring techniques that substitute any one all do not produce PSD.Therefore, every kind of sample and elapsed-time standards interval are not obtained the PDP value yet.On the contrary, can only obtain the amount " X " of preliminary surveying, for example, described " X " equals the turbidity or the light scattering intensity that draw mutually from the sample dispersion that applied stress.

For these the two kinds replaceable technology that be used for to characterize sample stability any, suppose that Instrument Design is appropriate because disperse phase has been applied stress, the X value will be along with the degree of particle aggregation effect monotone increasing.For the given stress level that applies, elapsed-time standards is longer, and the X value that usually records will be larger.Similarly, for given elapsed-time standards length, the stress level that applies is larger, and the X value is also larger usually.Therefore, in the situation based on the device that uses the particle size analysis instrument, also have the amount that derives from the amount X that records, it can be used for characterizing stability or the quality of the disperse phase of testing.The amount of these derivation includes but not limited to,

With

What can be used in the present invention is used for these substitute technologies particle size analysis, but the device that does not produce the method for PSD or PDP value diagrammatically is shown among Figure 23.

The particle size analysis instrument 80 of Figure 22 is replaced by sensor 180, and it comprises the light source 182 of light beam 184 by flow cell 186 projections.Then beam direction is as the optical sensor 188 of turbidity detecting device.When light beam passed flow cell 186, the increase of the particle aggregation effect of sample dispersion in mutually caused the reduction of beam intensity.Therefore, the signal V that is detected by turbidity detecting device 188 _XWeaken and indicated the particle aggregation effect to increase, show the second-rate of disperse phase sample.Signal V _XSupply to signal conditioner 190 from turbidity detecting device 188 by illustrated switch 189, arrive again computer control/processor 100, to produce from signal V _XThe quality X that obtains.

Interchangeable embodiment is that light scattering detector 192 receives the light of the particle scattering in the flow cell 186.The increase of particle aggregation effect causes the scattered light of direct light sensor 192 to increase, so that the signal V that produces in detecting device 192 _XEnhancing, shown that agglomeration increases and sample dispersion phase second-rate.Signal V _XSupply to signal conditioner 190 and computer control/processor 100 by switch 189, to provide from signal V _XThe quality X that draws.The description of the preferred embodiment (based on SPOS) among the sequence of operation of this replaceable unit among Figure 23 and the Figure 22 that summarizes above is substantially the same.Identical reference number represents same parts.

By the description of these embodiment, obviously, the stability of some disperse phase of research can be " multidimensional "-namely, and it can be referring to more than one physical mechanism.In these cases, the effective stress test of these disperse phase may need to use simultaneously the stress factor of more than one types-namely, by using the stress factor of multidimensional.In fact, people can be simultaneously combine above-mentioned two kinds even all three kinds of embodiment.For example and since particle with electric charge relatively high, and interparticle moving iron is relatively less, given disperse phase may be stable.In this case, may be to add specific electrolyte (with one or more concentration) to the effective means of its stress application systematically, make electric charge and the Coulomb repulsion on the particle can V _RAll reduce, these two kinds of actions all cause energy barrier height V _MAXReduction.Usually, the multaxial stress factor can be come specialized designs by two or more stress factors that are combined in independent usefulness in the embodiments described herein (being applied to various combinations and concentration/intensity).Again, these designs comprise: add acid (or alkali); The salt that adds adsorbing electrolyte and add non-absorption.

When this discussed end, looking back crucial design of the present invention and outstanding feature was of great use.Designed specific stress factor has been applied to given suspending liquid or emulsion, to accelerate the intrinsic stabilization process of going in the product, to be disclosed in the final defective that occurs in the final preparation.The present invention advise using substitute measure-be one or more stress factors-with the stability of prediction disperse phase, and final prediction runs through the performance that it specifies the disperse phase in shelf-life or serviceable life.Stress factor is barrier height V between the particle of disperse phase _MAXApproximate representation, thereby forecast information about stability and the quality of final products is provided.The fundamental purpose of stress factor is, quantitatively differentiate in the disperse phase of charge stable by V _MAXThe existing particle of amplitude domination between the clean effect disturbed of stability.Substantially, by using highly sensitive particle size analysis technology, apply one or more stress factors with system and be combined, by titration V systematically _MAX, the method for general introduction allows the degeneration of the potential disperse phase stability of calibration in the present invention.The above has explained in detail with the combination of the particle size analysis ability (LE-SPOS) of the sensitivity of exquisiteness from the method that one or more stress factors is applied to two kinds of different oil-in-water emulsion/disperse phase.These new methods are utilized correlated results variable " PDP ", and this variable provides V _MAXAlternative tolerance.Stress factor is unique to the explanation of the quantitative effect of PDP temporal evolution (PDP and t) (accumulative total and difference), and has consisted of the core of novelty of the present invention.

By the quantitative detection V with respect to the present invention's instruction _MAXThree kinds of basic concepts of the method ability of respective change (that is, reducing), this method is particular importance.The first, it minimizes, and has perhaps avoided together obvious change (that is, the variation of phasor) potential in the physical chemistry structure of initial preparation, and this will be produced by the various stress factors that applied excessive levels in addition.In addition, may produce visibly different disperse phase or emulsion with different physical features, and can expect that therefore having applied so excessive stress factor induces rear its performance different from the performance of initial dispersion phase.The second, can assess the stability of some the very unsettled disperse phase that can stand in addition routine even optimal dose stress now.For example, in some cases, according to the characteristic of the composition that comprises disperse phase, the stable difference between two kinds of preparations being determined by very little stress induced interference will need to measure accurately, with based on V _MAXIntrinsic critical difference is distinguished two kinds of stability between the level.The 3rd, this " fine setting " of stress factor response will greatly strengthen the comprehensive forecasting ability for assessment of the combination property method of disperse phase interested.

Top description has been instructed by one or more stress factors being applied to a plurality of batches of methods of assessing the stability of given disperse phase of same initial dispersion phase, wherein in when beginning (, the t=0 of nominal) each batch added different stress level or intensity.This method has been set up the form of a kind of " parallel processing ", wherein when having stress level to exist, with batch impact of measuring different stress levels of many samples.When studying relatively new disperse phase (that is, not having fine sign about the disperse phase of its stability and/or quality) by the stress test of accelerating, this " rough approximation " method is suitable especially.This method is effective setting up the optimum stress of interested disperse phase " profile " (namely setting up the effective stress horizontal extent for the given applied stress factor).This useful first step typically development before the production routine of disperse phase interested begins is employed.

Yet in case interested disperse phase has been set up the optimum stress profile, obviously, using method of the present invention can have the effect that is equal to from using different " serial processing " methods.That is to say, can be to single batch of the initial sample stress that increases gradually of (the being the cycle) level that applies repeatedly, to reach the unsettled beginning of quickening.Beginning-when being t=0, the given applied stress factor of given applied stress level can be applied in the single sample batch.After calculating PDP, through the suitable elapsed-time standards of regulation, then use identical stress factor, with the further stress application of higher level in same sample batch.This process can periodically repeat, and all PDP is determined at every turn.The PDP that obtains and t figure can expect that the curve by monotone increasing (" to being recessed on ") forms, the detailed performance of curve-namely wherein,

With t-the disclosed latent instability of disperse phase interested.For the stress application level of the increase of given series, initial (not stress application) disperse phase is more stable, and the PDP of generation and t figure get over " flat " (curvature is lower).The curve that produces is compared with the reference that obtains for the previously known sample or reference mark curve, and acceptable stability will allow the quality of product batches is monitored and verified.Therefore, the conventional commercial or private part that usually it can be used as standard quality assurance/quality control (QA/QC) program of using of the present invention, drawing can further become temporal evolution and the database of the evolution of refining, becomes the part of the standard openating procedure of given disperse phase.

New method of the present invention based on the supposition given disperse phase (be the intended size scope, d 〉=d ₀, by SPOS or other enough the particle aggregation effect of sensitive commercial measurement change) response that the given applied stress factor is used is sensitivity and the reproducible function of amplitude, elapsed-time standards and the disperse phase latent instability of stress level.Therefore, do not rely on the theoretical model (for example based on dlvo theory) of colloidal stability, the disperse phase of given type or the relative stability of emulsion can be by PDP and the elapsed-time standards of t(after stress application when applying the stress of one or more levels (being amplitude)) performance judge.By comparing than the hypothesis of the disperse phase of the specific sample more stable or more unstable (namely being respectively higher or lower quality) that uses method assessment of the present invention and actual PDP and t figure, this conception of species can be more readily understood.

Figure 24 A comprises PDP and the t of two series, pH figure.A series of drawing (solid-line curve) has represented from the real response of system's acquisition-namely, the vegetable oil emulsification liquid of early discussing is added up and stablize the ionic species (adding) that mixes when t=0.Another series of drawing (dashed curve) has shown " hypothesis " response, should " hypothesis " responds to get self similarity but more stable emulsion.What show among solid-line curve (and relevant data points) and Figure 18 comes to the same thing, and has represented the emulsion that contains electronegative drop to the response of " sour stress ".Reduce continuously pH, from 6.56(contrast, soft dot) to 5.65(sealing round dot), 5.13(seal square) and 4.46(seal triangle), cause the increase of time correlation variation in the droplet coalescence, be shown among Figure 18 and the 24A.Dashed curve has represented the hypothesis response that may derive from same sample, supposes that it is slightly more stable than the emulsion of solid-line curve representative.For given applied stress level (i.e. lower pH value), people still observe PDP to be increased with elapsed-time standards.Yet, suppose that the sample that (hypothesis) supposed is more stable before stress application, the amplitude of response (that is, the degree of droplet coalescence) is lower than any given t value.For reason previously discussed, when any given t value, the difference that derives from the PDP value of actual and assumes samples can be expected to be increased along with the increase of stress level.

Figure 24 B has shown actual and hypothesis PDP and t, and pH result's ratio of similitude is supposed hypothesis emulsion (dashed curve) even more stable than what represent among Figure 24 A.In this case, compare with the figure (solid-line curve) of the emulsion that derives from actual measurement, derive among the hypothesis PDP of the more stable assumes samples of this second supposition and the t figure even larger " inhibition " arranged.Similarly, Figure 25 A and 25B have shown reality and hypothesis PDP and the t of emulsion of the same race, and the comparison of pH figure is wherein with actual sample test (solid-line curve, all identical in all figure) to compare, two kinds of assumes samples (dashed curve) are for slightly more unstable and quite more unstable.

As the expansion of the above-mentioned concept of using about the present invention, further commented on the difference value that the experiment emulsion is observed in response to the mode of some stress factor.The research of vegetable oil emulsification liquid is used again a kind of mode of the inventive method as explanation, because many independent factor that greatly affect main dependent variables " PDP ", for example time, stress factor and stress level are arranged.Particularly, the stress factor of time correlation is helpful on a kind of indicative example of PDP impact.In order to verify, Figure 16 shown through the PDP of 28 hours vegetable oil emulsification liquid and t performance, its by the hybrid ionic kind that applies low concentration by towards unstable " promotion ".Unsettled clear evidence is until just displayed after about 24 hours.In order to realize this result, accelerate unstable (being the obvious increase of PDP) in shorter elapsed-time standards, adopt two kinds of different stress factors that identical emulsion is carried out inducing of system.Therefore, use and only to be designed within 1/4 normal need time (namely only in (approximately) 240 minutes or shorter time) to cause that the various levels of obvious measurable de-stabilising effect or two kinds of different stress factors of " intensity " are studied.

For example, vegetable oil emulsification liquid (the hybrid ionic kind of adding up stable) is applied sour stress (namely reducing pH), the results are shown in Figure 18 and the Table IV.For each stress level that applies or pH value, the response PDP of the emulsion that discovery is measured is with approx linear increase of elapsed-time standards t.When pH reduced, observe the PDP temporal evolution and increase gradually positive correlation, correlation coefficient r was from pH=5.65(Δ pH=-0.91) time 0.972 be increased to pH=4.46(Δ pH=-2.1) time 0.996.The value coincidence measurement PDP value that these are higher and apply the strong correlation that exists between the elapsed-time standards after the pH stress.

These find with concentration dependent, with hydrogen ion (H ⁺) to be adsorbed in specially the drop surface consistent, cause to repel potential energy V between particle _RAnd the energy barrier height V that produces _MAXReduce gradually, cause coalescent quickening.Obviously, the level of sour stress is higher, and the PDP value of increase is just better from the correlativity of different elapsed-time standards.In order to give this emulsion design the most effective stress test, will guarantee to carry out a series of other researchs, it is centered by the pH value more among a small circle that produces the highest r value.In Primary Study (Table IV), be 5.13 and obtained the highest r value (0.99) at 4.46 o'clock in the pH value.Therefore, lower series of experiments can be around these pH value designs.Because when pH=5.13, when time t=0, change immediately, the increase of pH increment is higher than 5.13, and for example 5.48 and 5.31, can set up threshold level (in PDP, not inducing direct variation when being lower than described threshold level).Similarly, the increase of pH increment is higher than 4.46, and for example 4.69 and 4.91, can be used for being presented at pH and be reduced at 4.46 o'clock, the progressive effect when time t=0 from 5.13.These and other experiment will be used to the stress level of optimizing given emulsion.Therefore, use the purpose of Δ PDP correlativity to be under different experimental conditions, differentiation can characterize significant stress factor scope and the concentration of given emulsion or disperse phase stability best.

At last, these explanations concentrate on the liquid dispersion phase, but must emphasize, the method for the present invention's instruction also can usefully be used for real solution.That is to say, some stress factor also can be applied in the solution, to induce wherein contained activity or the precipitation of non-active ingredient, finally causes the inverse variation in the solution that uses or apply.Compare with the product that lacks these predetermined substances, can hint that from the performance of benchmark or historical level or variation it is inferior for the particle in the given product solution.Therefore, for real solution, precipitation will be can disturb the primary product of inducing by the stress of gentleness in the of inferior quality product.Again, can be with to PSD(for example, the particle size relevant with precipitation changes) variation enough sensitivity analytical technology and suitable stress factor/level is applied to combination in the solution interested.This method allows quickening based on the stress test of the product of solution, thereby allows the product of inferior quality to make a distinction from high-class product.

According to the characteristic of single analyzed product and application thereof, and as the consideration of acceptable stability criterion, the End-point Prediction of quickening stress studies described herein is temporary transient.For example, in the situation that product very expensive (namely valuable), based on the stress test of accelerating, the decision of accepting or refuse production batch has very large economic consequences, and application of the present invention can be based on number of false positives being dropped to the specific terminal point of minimum height.That is to say, considering to have higher error of the second kind, and the selectivity of test will be as far as possible near 100%.On the contrary, have at product in the situation of main health consequences, the result that stress factor is applied in given disperse phase or the emulsion will be based on super-sensitive terminal point, and it drops to false negative quantity minimum.That is to say, consider the higher error of the first kind that certainly exists, the sensitivity of test will be as far as possible near 100%, because this possibility of result is very important.Obviously, sensitivity and selectivity have that opposite relation-namely, when sensitivity increased, selectivity descended, and vice versa.The common technology relevant with sensitivity and selectivity is known with receiver/operation characteristic.In other cases, it is not crucial using the cost of these methods or consequence, and final products and test do not need so accurate standard, the cost-effectiveness balance between the test-types of employing, and their sensitivity and selectivity can both reach.Obviously, the manufacturer will make on basis independently and thisly determining.As possible, when making the decision of these keys, every kind of product is applied more than one stress factors and/or condition.Finally, for given product, the data/experience that adds up in time will be determined the best applications of the method that the present invention instructs.

The invention is intended to the quality for assessment of disperse phase and emulsion, the response that wherein obtains by particle size analysis optionally when differentiating the product of inferior quality (ideally, their use or management before) be highly sensitive and/or single-minded.The process of the present invention's instruction is depicted as " Performance Evaluation " method, before packing, uses when production cycle finishes, and also can before commodity distribution, be used for testing the final packaging unit of a certain quantity.Invention has been described although the above is according to the stability test of accelerating, and this emphasizing only is illustrative, and do not mean that in any form and limit it.The technician in dispersion technology field will determine other suitable modification of the present invention.For example, the method for the present invention instruction is used for optimizing the product of large-scale commercial applications disperse phase manufacturing and processing work, so that the loss of final batch failure and/or commercial product drops to and minimumly expects.Therefore, these methods also can be applied at the production period of product the product of predefined " in the production ".Exist the multiple data that produced by these researchs to can be applicable to the mode of specific production or commercial operation.Expectation is implemented the present invention in the mode of product quality that improve to make, for example set up some product specification determine performance " by " or " not passing through " condition.These can be used by the different time within the whole cycle in serviceable life of production, dispensing and/or the application of product.

Critical " moment " during disperse phase on any scale or emulsion are produced can be processed the gap in key and be occured.These moments often relate to different mixing or applying step; For the processing of potpourri, disperse phase or emulsion or finally use and to manufacturer independently, its physical and chemical condition is specific.Or even when disperse phase by same manufacturer when different productions are produced, critical moment also may be different.Therefore, the application of institute of the present invention method taught will allow to optimize the whole production that manufactures a product and many aspects in cycle in serviceable life.The industry of the commercial or special disperse phase for preparing or emulsion or the private producer can not only improve its final mass or distribute safely, have also prolonged to be assigned to the current storage period of utilizing product, have further reduced potential economic loss or waste.Method presented here is used the physical chemistry error that also can improve the product counter stress, and this stress may occur in transportation, storage and by during terminal user's exposure or the final service condition that applies.These are included in any horizontal processing product until contingent excessive risk event between the operating period.Finally, method described herein is used separately to be essentially in many cases privately owned mode.For example, these can be based on (but being not limited to) following normal condition: the formation of disperse phase or emulsion; The type of the stress factor that applies; Obtain disperse phase or the emulsion of expectation mode (for example, mechanical raking, grind, homogenize, polymerization etc.); Order by merging; The producer's experience; And the physical condition of manufacturing, transportation and end user environment.Therefore, method described herein and embodiment can be at the stages of research and development and dispensing disperse phase and emulsion, use in routine is produced the effort of the consumer goods of high-quality and safety.

Although with reference to the preferred embodiments of the present invention it has been carried out special demonstration and description, those skilled in the art can understand, and wherein can carry out variation on aforementioned and other form and the details to it, and not deviate from the spirit and scope of the present invention.

Table I

PDP and t, the regretional analysis of pH, data derive from butter fat (whole milk) emulsion (Fig. 5-7) that has applied sour stress

Batch #1(0608)

Batch #2(0612)

Batch #3(0615)

Table II

PDP and t, [CaCl ₂] regretional analysis, data derive from butter fat (whole milk) emulsion (Figure 10-13) that has applied lime chloride stress

Batch #1(0608)

Batch #2(0612)

Batch #3(0615)

Table III

PDP and t, the regretional analysis of [salt], data derive from the oil-in-water type vegetable oil emulsification liquid (Figure 17) that has applied sodium chloride stress

Table IV

PDP and t, the regretional analysis of pH, data derive from the oil-in-water type vegetable oil emulsification liquid (Figure 18) that has applied sour stress

Claims (27)

1. method of be used for determining sample stability, described sample comprises the solid that is suspended in the liquid-carrier or the disperse phase of droplet particles, wherein between particle potential barrier to have suppressed adjacent particles closer to each other to being enough to allow the short distance attraction force acts owing to strong that irreversible agglomeration occurs, described method comprises:

To the described sample stress application factor, to reduce the height of potential barrier between described particle, so that the accelerated particle agglomeration; And

Detect the increase of the described particle aggregation speed of action as the tolerance of described stability.

2. the method for claim 1, wherein said stress factor has reduced the surface charge on the described particle by changing the pH value of described sample.

3. method as claimed in claim 2, wherein said particle has net negative charge, and wherein said stress factor is acid or the buffering acid that joins in the described sample with the pH value that reduces described sample.

4. method as claimed in claim 2, wherein said particle has clean positive charge, and wherein said stress factor is alkali or the buffer base (BB) that joins in the described sample with the pH value that improves described sample.

5. the method for claim 1, wherein said stress factor is the adsorbing electrolyte that joins in the described sample, with allow suitable electric charge from the ionic adsorption of separating to the surface with opposite charges of described particle, to reduce the net charge on the described particle.

6. method as claimed in claim 5, wherein said particle has net negative charge, and the described ion that comprises from adsorbing electrolyte from the ion of separating with positive charge, the surface conjunction of itself and described particle, and reduce net charge on the described particle, thereby reduce the described height of potential barrier between described particle.

7. the method for claim 1, wherein said stress factor is the salt that joins in the described sample, so that produce from motion ion that separate, Coulomb repulsion between the partly shielding effect charged particle, thereby has promoted their agglomeration.

8. method as claimed in claim 7, wherein said stress factor are to be applied in as simple monovalent salt.

9. method as claimed in claim 8, wherein said monovalent salt is sodium chloride.

10. the method for claim 1, wherein said stress factor is to apply with continuous increment at the interlude interval, thereby the stress level that causes being added in the described sample of stress uprises continuously, and the described step that detects the increase of described particle aggregation effect repeats behind each stress factor increment.

11. the method for claim 1, wherein said sample is divided into a plurality of batches, the described step that wherein described stress factor is applied to described sample comprises that the described stress factor with varying level is applied in each batch, and wherein detects described step execution after the one or more time interval Δ t of process that the effect of particle aggregation described in each batch increases.

12. method as claimed in claim 11 also provides the control batch of described sample, stress factor is not applied in the described control batch, and through detecting the increase of particle aggregation effect in the described control batch after the described time interval Δ t.

13. method as claimed in claim 11 wherein is right after after described the applying of described stress factor, detects the step of particle aggregation effect degree in each described batch.

14. method as claimed in claim 11, the described step that wherein detecting described particle aggregation effect increases also comprises the particle size distribution of measuring each batch on the proper range of particle size, and calculating the number percent of disperse phase according to the particle size distribution of each measurement, the number percent of described disperse phase is the volume-percentage by weight of fat drop in disperse phase that occupies particle size range.

15. method as claimed in claim 14 comprises that further the number percent of the described disperse phase that calculates each described stress factor level is with the rate of change of elapsed-time standards.

16. method as claimed in claim 14 comprises that further calculating is for the increase of the number percent of the described disperse phase of the described stress factor level variation of given elapsed-time standards value per unit.

17. a method according to claim 1, be used for determining the equipment of sample stability, described sample comprises the solid that is suspended in the liquid-carrier or the disperse phase of droplet particles, wherein between particle potential barrier to have suppressed adjacent particles closer to each other to being enough to allow the short distance attraction force acts owing to strong that irreversible agglomeration occurs, described equipment comprises:

With the device of described offering sample in the test container;

The described sample stress application factor in the described container is reduced barrier height between described particle, with the device of accelerated particle agglomeration; And

For detection of the increase of the described particle aggregation speed of action device as described stability metric.

18. equipment as claimed in claim 17, wherein said increase for detection of the described particle aggregation speed of action comprises high sensitivity detector as the device of described stability metric.

19. equipment as claimed in claim 18, wherein said high sensitivity detector are the single-particle sensors.

20. equipment as claimed in claim 19, wherein said detecting device are single-particle optical sensor SPOS.

21. equipment as claimed in claim 18, wherein said high sensitivity detector comprise sensing in response to described particle in given interval, pass the given area the X value, and output as the detecting device of this X value of stability metric.

22. equipment as claimed in claim 21, wherein said X value are in response to the tolerance of optical attenuation of the turbidity of described sample dispersion phase.

23. equipment as claimed in claim 21, wherein said X value are the tolerance at the scattered light intensity in the given angle scope of the described particle of described sample dispersion phase.

24. equipment as claimed in claim 17, the wherein said device that increases for detection of described particle aggregation effect comprises sensitivity, proportioning device, is used for determining owing to described stress factor described applies the described sample degree of less stable that becomes that makes.

25. equipment as claimed in claim 24, wherein said sensitivity, proportioning device produce particle size distribution (PSD), and it is shown as size on the normal grain range of size and larger and indicate the function of the afterbody of the major diameter separator particle that agglomeration increases than described normal grain size with particle concentration.

26. equipment as claimed in claim 24, the device of wherein said increase for detection of described particle aggregation effect comprise that sensing passes the value of given area and exports this value as the detecting device of the tolerance of stability in given interval in response to described particle.

27. equipment as claimed in claim 17, also be included in described stress factor is applied to described sample in the described container after, be used for described sample is fed to from described test container the device of the described device that increases for detection of described particle aggregation effect.

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