Oil-in-water emulsion as delivery means

FIELD: medicine.

SUBSTANCE: invention relates to food, pharmaceutical and cosmetic industry, in particular deals with oil-in-water emulsion, containing disperse oil drops which have nano-size self-arranging structured internal contents, including: (i) oil, (ii) lipophilic additive (LPA), (iii) hydrophilic domains in form of drops or small canals, containing water or non-water polar liquid, and continuous water phase, which contains emulsion stabilisers or emulsifiers, in which oil drops with diametre from 5 nm to 900 mcm possess nano-size self-arranging structuring with formation of hydrophilic domains with diametre from 0.5 to 200 nm due to presence of lipophilic additive.

EFFECT: invention provides structures able to solubilise not only lipophilic but at the same time hydrophilic and/or amphiphilic, or hydrotropic, or crystalline components.

8 cl, 16 ex, 18 dwg

 

The technical field

The present invention relates to emulsions of the oil-in-water, in which the dispersed oil droplets show self-organizing nanostructure.

Prior art

Emulsion in the industry.

Emulsions are typically colloidal systems present in many manufactured products, such as foods, cosmetics or pharmaceuticals. They are formed from droplets of oil dispersed in a continuous aqueous phase. Dispersed oil droplets are stabilized by surface-active molecules, which form the adsorption layer around the droplets of oil. For dispersing the oil phase in the continuous aqueous phase homogenizers are used, which allow to obtain oil droplets of different sizes (with a radius of approximately 100 nanometers (nm) to several hundred micrometers). The formation of the adsorption layer around the droplets of oil in the process stage homogenization makes drops of oil kinetically stable to coalescence, flocculation or coagulation. Surface-active substances used in products based emulsion of oil-in-water, can be either a low molecular weight hydrophilic surfactants, such as Polysorbate, lysolecithin, derivatives of monoglycerides, etc. or polymers, such as proteins, for example gelatin or milk proteins, soy -, or polysaccharides, such as gum Arabic or xanthan gum, or mixtures of the above.

Products based emulsion of oil-in-water commonly used in the food, cosmetic or pharmaceutical industry. Famous food-based emulsion of oil-in-water are, for example, milk, mayonnaise, salad dressings or sauces. Well-known products on the basis of emulsions of oil-in-water used in the cosmetic or pharmaceutical industry, are lotions, creams, cosmetic lotions, pills, tablets, etc. Drops of oil in such products usually consist, for example, from triglycerides, diglycerides, waxes, esters of fatty acids, fatty acids, alcohols, mineral oils or hydrocarbons.

The emulsion used either as a raw material, intermediate or finished product, or as an additive to the finished product.

Emulsions as a vehicle for delivery

One of the applications of emulsions in the industry is their use for delivery of active compounds, such as fragrances, vitamins, antioxidants, nutraceutic, phytochemical compounds, medicines and other Receiving active components requires the use of appropriate tools to deliver an effective amount of the active component trebuemoe the site of its action. Emulsion oil-in-water are commonly used as delivery systems, because they have such a useful property, as increased solubility of lipophilic active compounds in the oil. In EP 1116515 is an example of the application of the emulsion to control the intensity of the fragrance, in which the hydrophobic active ingredient, for example an aromatic component, intervenes in the matrix in the extruder with the formation of emulsions of oil-in-water to improve the stability of the introduced active ingredient during subsequent processing of the product. In WO 00/59475 as an example, the pharmaceutical emulsion of oil-in-water describes a composition and method for improved delivery can ionize hydrophobic therapeutic agents, which are mixed with an ionizing agent, surface-active agent and a triglyceride with emulsion oil-in-water. WO 99/63841 as an example of the use of emulsions in the food sector describe compositions containing phytosterol having improved solubility and dispersibility in the aqueous phase due to the formation of emulsions or microemulsions.

In addition, if oil droplets in the emulsions of the oil-in-water is excessively small, for example, of the order of a few nanometers (nm) to about 200 nm in diameter, this emulsion is called a microemulsion or nanoemulsion the first oil-in-water (Evans, D.F.; Wennerström, H. (Eds.); "The Colloidal Domain, Wiley-VCH, New York (1999)). These emulsions are transparent and thermodynamically stable, and therefore qualified specialist in this field can distinguish them from conventional emulsions are thermodynamically unstable and in most cases, the cloudy.

Other delivery systems are particles of surfactant mesophases described by Gustafsson et al. (Gustafsson, J.; Ljusberg-Wahren, H.; Almgren, M; Larsson, K.; Langmuir (1997), 13, 6964-6971).

Description of the invention

From prior art it is known that the dispersed oil droplets in the emulsions of the oil-in-water are used as a means of delivery of lipophilic molecules that dissolve in the droplets of oil. The disadvantage of emulsions of this type, as delivery systems is that they cannot be used for crystalline (i.e. present in crystalline form), hydrophilic or weakly amphiphilic molecules individually or in combination with lipophilic compounds due to the lack of molecular solubility of the active agent in the oil phase. Particularly difficult is the delivery of crystalline or amphiphilic or hydrotropic connections, since they show a tendency to violation of the stabilizing functions of emulsifiers and, as a consequence, can destabilize the emulsion.

The present invention is based on the discovery of new NAS is dimensional self-assembled structures within the usual drops of oil. Patterns are formed by adding lipophilic additive (LPA) to the drops of oil. Such structures can solubilisate not only lipophilic components, but at the same time and hydrophilic and/or amphiphilic, or girotropnye, or crystalline components. Nanoscale self-organizing patterns inside drops of oil consist mainly having the nano and thermodynamically stable hydrophilic domains, i.e. water droplets, columns or tubules. These have the nano-domains, which are formed spontaneously (thermodynamic mechanism) inside drops of oil emulsions, stabilized LPA. The hydrophilic portion of the molecule LPA is part of the structure of the hydrophilic domain. Hydrophilic domains may have a size of 0.5 to 200 nm in diameter, preferably from 0.5 to 150 nm in diameter, more preferably from 0.5 to 100 nm in diameter and most preferably from 0.5 to 50 nm.

In the context of describing "hydrophilic domain consists of water domains and hydrophilic head region of the LPA molecules. Due to their excessively small size, they also have a large surface area, which is suitable to solubilize a variety of different connections.

The emulsion of the present invention is clearly different from the traditionally known emulsions, such as double emulsion water-in-oil-in-water (W/M/In). In/is/(water-in-oil-in-water double emulsions are emulsions of oil-in-water, in which oil droplets contain water droplets of micron size (Garti, N.; Bisperink, S.; Curr. Opinion in Colloid &Interface Science (1998), 3, 657-667). Drops of water inside the dispersed drops of oil double emulsions are formed (dispersed) by supplying mechanical energy, such as homogenization, and consequently are thermodynamically unstable and nesavissimaja. The diameter of the inner water droplets in the/M/In double emulsion exceeds 300 nm. The emulsion of the present invention can be easily distinguished from the normal I/M/In double emulsions, since the formation of nanoscale self-organizing patterns inside drops of oil emulsion of the present invention occurs spontaneously and is called thermodynamic mechanism, and the average diameter of water droplets or tubules is less than 200 nm.

Thus, the invention is directed to oil droplets, which contain nano-sized self-organizing structure with hydrophilic domains. The concept of "self" or "self-organization" refers to the spontaneous formation of aggregates (associates) or nanostructures separate molecules. Molecules in self-assembled structures take appropriate location, due only to their structural and chemical properties, under the action of intermolecular forces, such as hydrophobic hydration or electrostatic the definition of force (Evans, D.F.; Wennerström, H. (Eds.); "The Colloidal Domain, Wiley-VCH, New York, (1999)). The result of self does not depend on the process and corresponds to a state of minimum energy (stable equilibrium) system.

JP 2004008837 discloses an emulsion of oil-in-water, which contains a water-soluble solid particles present in the droplets of oil. The particles have a size from 200 nm to 10 μm. Particles are formed in the emulsion water in oil (W/M) as a result of dehydration (i.e. the process is not spontaneous) before dispersion slurry of solid particle/oil (S/O) in the aqueous phase, using a process of emulsification with a porous membrane.

WO 02/076441 discloses the use of microemulsions alcohol in the fluorocarbon as a precursor for the preparation of solid nanoparticles. The nanoparticles have a diameter of less than 200-300 nanometers. The formation of nanoparticles occurs spontaneously, and is caused by cooling the microemulsion is a precursor to a temperature below about 35°C or by evaporating the alcohol from the microemulsion predecessor or dilution of the microemulsion suitable for this purpose polar solvent.

US 2004/022861 discloses a double emulsion/M/, in which oil droplets contain microscopic liquid aqueous phase containing protein or other hydrophilic agent. All double emulsion is sprayed, for example, in liquid nitrogen through a capillary nozzle DL is receiving carrier protein microparticles.

In all of these examples describes espontanea the formation of a solid hydrophilic (nano)particles using the/M microemulsions or/M or double emulsions In/M/, and therefore requires an external trigger for hardening the hydrophilic domains within drops of oil. On the formed (nano)particles environmental factors such as temperature, pH or properties of the fluid particles, does not have a significant impact. It should be mentioned that at the normal I/M microemulsions, in which water droplets of the liquid, and the liquid, these environmental factors have a strong influence.

Numerous scientific studies have shown that the type of emulsion (M/or/M)formed by homogenizing the corresponding Winsor system (Winsor I (/M microemulsion plus excess oil) or Winsor II (M/In the microemulsion plus excess water))is the same as it is formed in the microemulsion phase that is in equilibrium with excess continuous phase. For example, emulsification/M microemulsions plus excess water system (Winsor II) provides at a sufficiently high concentrations of surfactants, i.e. exceeding the critical concentration of surfactant in the oil phase SSoilthe emulsion/M, continuous phase which itself is a microemulsion In/Is (..Binks, Langmuir (1993) 9, 25-28). This means that, when a microemulsion/M diluted aqueous phase, the emulsion/M prevails over the emulsion M/C. Binks et al. (..Binks, Langmuir (1993) 9, 25-28) explained this behavior in the framework of the distribution of surface-active substances between water and oil phases in accordance with rule Bancroft (Bancroft''s rule) (W.D.Bancroft, J. Phys. Chem. (1913) 17, 501): if surface-active substance is accumulated in the oil phase, i.e. better soluble in oil than in the aqueous phase, the resulting emulsion will always type/M and not type M/C. For the preparation of emulsion M/from micro-emulsions/M or systems Winsor II (microemulsion/M plus excess water) it is necessary that the surface-active substance has undergone phase inversion, i.e. changing its solubility of the oil-soluble (education/M emulsion) in water-soluble form (education M/In the emulsion) (.Izquierdo et al., Langmuir (2002) 18, 26-30). When using non-ionic surfactants, such as alkylalkoxysilane, for example, C12EO4this can be achieved by cooling the system with 40-50°C (PIT temperature) to below 25°C. It is completely different from the present invention in which the phase behavior of lipophilic additive (LPA; forms a microemulsion In/M at room temperature) correlates with the formation of emulsion M/B, in which the oil droplets, containing hydrophilic domains stabilize the usual water-soluble emulsifier. In this case, the hydrophilic domains are liquid and not solid. The microemulsion/M or oil-containing hydrophilic domains can be diluted (dispergirujutsja) in the aqueous phase without phase inversion and release hydrophilic domains within the dispersed droplets of oil, and without the necessity of hardening internal hydrophilic domains in drops of oil before the stage of dispersion.

According to the invention spontaneous formation having nano-sized, self-organizing patterns inside drops of oil can be realized in different ways. One of them is adding a lipophilic additive (LPA), which promotes the spontaneous formation having nano-sized, self-organizing patterns in the oil phase before the stage of homogenization. Another way involves adding a lipophilic additive (LPA) to the emulsion product before or after the stage of homogenization. In this case, the lipophilic additive is dissolved in the oil droplets and leads to the spontaneous formation having nano-sized, self-organizing patterns inside drops of oil. As a homogenizer can be used in the usual industrial or laboratory homogenizer, such as a piston homogenizer (Rannie, rotor-stator mixer Kinematica, to Llodra mill, the Stephan mixer, a cell with high stress shear Couette or device for membrane emulsification. Moreover, for the preparation of the emulsion described in the present invention, is also suitable ultrasonic mixer, the mixer with the injection of steam or household mixer. Spontaneous formation having nano-sized, self-organizing patterns inside drops of oil does not depend on the supply of energy used for the preparation of the emulsion, and the sequence of addition of LPA. This means that the technique of microfluidizer (Microfluidics) also suitable for the production of emulsions of the present invention.

Following through preparation of an emulsion of the present invention is the use of hydrotropes or agents that Deplete water patterns, or spontaneous emulsification, which can be chemical or thermodynamic mechanism (Evans, D.F.; Wennerström, H. (Eds.); 'The Colloidal Domain', Wiley-VCH, New York, (1999)).

Another way of preparing the emulsion of the present invention is a combination of spontaneous formation having nano-sized, self-organizing patterns inside drops of oil with spontaneous formation of drops of oil, i.e. emulsions in General the present invention, by adding a biopolymer type diblock copolymers or apoprotein, such as conjugates or koatservatov it is a protein-polysaccharide or hybrids of balakrishanan, protein-protein, or polysaccharide-polysaccharide, or mixtures of polymers or biopolymers, or low molecular weight surfactants.

The composition of the emulsion

The present invention relates to emulsions of the oil-in-water, in which oil droplets (with diameters from 5 nm to hundreds of micrometers) are nanoscale structurization with hydrophilic domains formed by using a lipophilic additive (LPA). LPA can be added as such or prepared in situ chemical, biochemical, enzymatic or biological means. The number of drops of oil present in the emulsion of the present invention (the volume fraction of drops of oil), corresponds to their number, usually used in products based on conventional emulsion oil-in-water.

More specifically, the present invention is directed to emulsion oil-in-water containing dispersed oil droplets having a self-organized nanoscale structured content, including:

(a) an oil selected from the group consisting of mineral oils, hydrocarbons, vegetable oils, waxes, alcohols, fatty acids, mono-, di - or triacylglycerides, essential oils, aromatic oils, lipophilic vitamins, esters, nutraceutical, terpinol, terpenes and mixtures of the above,

(b) a lipophilic additive (LPA) or a mixture lipophilin the x and hydrophilic additives, with the final value of the HLB (figure hydrophilic-lipophilic balance) below about 10, preferably below 8,

(C) hydrophilic domains in the form of drops, columns or tubules containing water or non-aqueous polar liquid, such as a polyol,

and

continuous water phase, which contains the emulsion stabilizers or emulsifiers.

In the context of the description of "lipophilic additive" (also denoted by the abbreviation "LPA") refers to a lipophilic amphiphilic agent, which spontaneously forms a stable, having nano-sized, self-organizing patterns in the dispersed oil phase. Lipophilic additive (mixture) selected from the group consisting of fatty acids, esters sorbitan, mono - or diesters of propylene glycol, pegylated (PEG = polyethylene glycol + -ylaled = pilirovanny) = PEG fatty acids, monoglycerides, derivatives of monoglycerides, diglycerides, PEG vegetable oils, esters of polyoxyethylenesorbitan, phospholipids, kefallinos, lipids, esters of sugars, simple esters of sugars, esters of sucrose, polyglyceryl esters and mixtures of the above.

According to the first variant the practical implementation of the invention, the emulsion oil-in-water form oil droplets having an internal structure selected from the group consisting of L2patterns or the combination of L2 oil structure (microemulsion or drops isotropic liquid) in the temperature range from 0°C to 100°C.

According to the second variant the practical implementation of the invention, the emulsion oil-in-water forms drops of oil with L2the structure of microemulsion or drops isotropic liquid) in the temperature range from 0°C to 100°C.

According to a third variant of the practical implementation of the invention, the emulsion oil-in-water form oil droplets having an internal structure selected from the group consisting of L2structure (microemulsion or drops isotropic liquid) or liquid crystal (LC) structure (e.g., reversible micellar cubic, two-dimensional reversible-continuous cubic or reversible hex) and their combinations in the temperature range from 0°C to 100°C.

According to the fourth variant of the practical implementation of the invention, the emulsion oil-in-water forms drops of oil with the internal structure of the LC in the temperature range from 0°C to 100°C.

According to the fifth variant of the practical implementation of the invention, the emulsion oil-in-water form oil droplets having an internal structure selected from the group consisting of structures L3, combination of structures L2and L3the combination of lamellar liquid crystalline (Lα) and L2patterns and combinations of Latinate crystal and L 2patterns in the temperature range from 0°C to 100°C.

According to the sixth variant of the practical implementation of the invention, the emulsion oil-in-water form oil droplets having an internal structure which is a combination of the previously described structures in the temperature range from 0°C to 100°C.

All of the above internal structure can certainly be determined by SAXS (small-angle x-ray scattering) analysis and cryo-THEMES (transmission electron microscopy) (Qiu et al. Biomaterials (2000) 20, 223-234, Seddon. Biochimica et Biophysica Acta (1990) 1031, 1-69, Delacroix et al. J. Mol. Biol. (1996) 258, 88-103, Gustafsson et al. Langmuir (1997) 13, 6964-6971, Portes. J. Phys.: Condens Matter (1992) 4, 8649-8670) and fast Fourier transform (FFT) cryo-THOSE images.

In some fields of use can also be used in temperatures above 100°C (e.g., temperature autoclaving), and it is covered by the present invention. Lipophilic additive (LPA) can be mixed with hydrophilic additive (having an HLB above 10) in an amount such that the total HLB of the mixture did not exceed 10, or preferably 8. Additive (mixture) may also be prepared in situ chemical, biochemical, enzymatic or biological means.

The number of added lipophilic additive is denoted by α. α is defined as the ratio LPA/(LPA + oil)·100. α is preferably higher than 0.1, more predpochtitel what about - above 0.5, more preferably above 1, most preferably higher than 3, even more preferably higher than 10, and most preferred is above 15. The ratio α=LPA/(LPA + oil)·100 is preferably less than 99.9, more preferably less than 99,5, even more preferably less than 99,0, even more preferably at least 95, and most preferably less than 84 and most preferred is less than 70. Any combination between the lower and upper limits of the range are included in the scope of the present invention. α can be expressed in wt.% or in mol.%. The lower and upper bounds of α depends on the properties of selected oils and LPA, such as polarity, molecular weight, dielectric constant, etc., or physical characteristics, such as the critical aggregation concentration of LPA in the phase drops of oil.

The emulsion is stabilized by emulsifier (also known as a primary emulsifier), suitable for stabilization drops conventional emulsion oil-in-water. The emulsion may be subjected to aggregation (flocculation) or not depends on the used emulsifier. Emulsifier selected from the group consisting of low molecular weight surfactants having HLB>8, gelatin, proteins, for example, milk proteins or soy peptides, protein hydrolysates, block copolymers, surface active hydrocolloids such as gum Arabic, xanthan to the copper, biopolymers type diblock copolymers or apoprotein, such as conjugates or koatservatov it is a protein-polysaccharide or hybrids of protein-polysaccharide, protein-protein, or polysaccharide-polysaccharide conjugates or koatservatov it or mixtures of polymers and biopolymers.

The emulsifier may also be mixed with LPA or with butter or with LPA, and butter. This means that the emulsifier may partially be present inside drops of oil and to influence internal nanoscale self-organizing structure.

The ratio β = emulsifier/(LPA + oil + emulsifier)·100 describes the amount of emulsifier used to stabilize the drops of oil relative to the oil content plus LPA. β is preferably higher than 0.1, more preferably above 0.5, most preferably greater than 1 and most preferred above 2.

The ratio β = emulsifier/(LPA + oil + emulsifier)·100, preferably less than 90, more preferably below 75 and most preferably below 50. Any combination between the lower and upper limits of the range included in the scope of the present invention. β can be expressed in wt.% or in mol.%. The lower and upper limit of β depends on the properties of the selected emulsifier, oil and LPA.

Various active components can solubilisates in nanoscale self organizing structured content drops of oil. They can be the ü soluble in oil, insoluble in oil, crystalline or water soluble components selected from the group consisting of nutraceutical, such as lutein, esters of lutein, β-carotene, tocopherol, tocopherol acetate, tocotrienol, lycopene, Co-Q10, flax seed oil, lipoic acid, vitamin b12, vitamin D, α - and γ-polyunsaturated fatty acids, phytosterols, flavonoids, vitamin a, vitamin C or its derivatives, sugars, additions to foods, functional ingredients, food additives, plant extracts, medicaments, drugs, pharmacologically active components, cosmetically active ingredients, peptides, proteins or carbohydrates, flavors, salts and fragrances.

In the emulsion oil-in-water according to the invention the lipophilic additive selected from the group consisting of myristic acid, oleic acid, lauric acid, stearic acid, palmitic acid, PEG (polyethylene glycol) 1-4 stearate, PEG 2-4 oleate, PEG-4 dilaurate, PEG-4 dioleate, PEG-4 distearate, PEG-6 dioleate, PEG-6 distearate, PEG-8 dioleate, PEG 3-16 castor oil, PEG 5-10 hydrogenated castor oil, PEG 6-20 corn oil, PEG 6-20 almond oil, PEG-6 olive oil, PEG-6 peanut oil, PEG-6 palm kernel oil, PEG-6 hydrogenated palm kernel oil, PEG-4 capric/Caprylic triglycerides, mono -, di-, three-tetrapyrrol vegetable oil and sorbitol, pentaerythritol di-, tetrastearate, isostearate, oleate, kaprilat or caprate, polyglyceryl-3-dioleate, -stearate or-isostearate, polyglyceryl 4-10 pentolate, polyglyceryl-2-4 oleate, -stearate or-isostearate, polyglyceryl-3 dioleate, polyglyceryl-6 dioleate, polyglyceryl-10 trioleate, polyglyceryl-3 distearate, mono - or diesters of propylene glycol and fatty acids (C6-C20, monoglycerides of fatty acids With6-C20derived lactic acid and monoglycerides, derivatives of lactic acid and diglycerides, diacetylated esters of tartaric acid and monoglycerides, triglycerin-monostearate-cholesterol, phytosterol, PEG 5-20 soy Sterol, PEG-6 sorbitan Tetra-, exactearth, PEG-6 sorbitan of tetrazolate, sorbitan of monolaurate, sorbitan of monopalmitate, sorbitan of montroseite, sorbitan mono - and tristearate, sorbitan of monoisostearate, sorbitan of sesquioleate, sorbitan of sesquistearate, PEG 2-5 olejowego simple ether, PEG 2-4 lauric simple ether, PEG-2 cetyl simple ether, PEG-2 stearic simple ether, distearate sucrose, dipalmitate sucrose, ethyloleate, isopropylmyristate, isopropylpalmitate, ethyllinoleate, isopropylmalate, poloxamers, phospholipids, lecithins, kefallinos, oat lipids and lipophilic amphiphilic lipid is in other plants; and mixtures of the above.

Emulsion oil-in-water according to the invention typically has a liquid form. According to another variant of the invention, the emulsion is dried and has the form of a powder.

Emulsion oil-in-water according to the invention is either a finished product or Supplement. The amount of additive in the final product is not critical and may vary.

The emulsion described in the present invention, an emulsion of a new type, which is called by the authors of this application 'ISAMULSION' in order to indicate the specific nature of drops of oil containingInternallySelfAssembled (internal self-organizing structure, and in order to separate the emulsion of the present invention from conventional emulsions oil-in-water double emulsions In/M/, including nano - and micro-emulsions in which the oil droplets are not self-organizing patterns of nanoscale with hydrophilic domains. Drops ISAMULSION mainly consist of drops of oil that are self-organizing structure of nanoscale with hydrophilic domains. This structure can be lamellar liquid crystal plate or crystal, or may be of a reversible nature, including L2, microemulsion, isotropic liquid phase, hexagonal micellar cubic or two-dimensional-continuous cubic phase. Patterns in mass the phase may appear as a single nanostructure or as a mixture of various nanostructures.

Thus, the aim of the present invention is the provision of a new composition of the emulsion oil-in-water, which can be used for delivery of active and/or functional ingredients in food products, pet food, nutraceutical, functional foods, new, cosmetic products, pharmaceutical, medicinal or agrochemical industry.

Brief description of figures

Figure 1 shows the structure found inside drops of oil ISAMULSION, as a function of α=100·LPA/(LPA + oil).

Figure 2 shows cryo-THOSE micrograph of a typical ISAMULSION.

Figure 3 shows a sample of small-angle scattering of x-rays (SAXS) emulsion ISAMULSION, total oil phase (nanostructured LPA), which was used for cooking ISAMULSION, and the corresponding conventional emulsion (without LPA, without the nanostructures). A.I. means an arbitrary unit of measurement for all shapes.

Figure 4 shows a sample of small-angle scattering of x-rays (SAXS) emulsions ISAMULSION containing various amounts LPA, i.e. with different values of α (α=100·LPA/(LPA+oil)).

Figure 5 shows the stability of the internal structure of drops of oil in time, is investigated by determining the small-angle scattering of x-rays (SAXS) (researched the same ISAMULSION, as in Fig.). It is seen that after 4 months was not observed changes in the internal structure of drops of oil, forming an ISAMULSION.

Figure 6 shows the reversibility of the internal structure of drops ISAMULSION during heating and cooling, as measured by the small-angle x-ray scattering (SAXS) (same ISAMULSION that and figure 3). It shows the reversibility of the formation of structure after heating and cooling. SAXS curves obtained during cooling to 58, 39 and 25°C, superimposed on the SAXS curves obtained in the process of heating to 58, 39 and 25°C respectively.

7 shows cryo-THE image drops of oil ISAMULSION (in the presence of LPA, with nanostructure) (a) in comparison with drops of the corresponding conventional emulsion (in the absence of LPA, without nanostructures) (b). Note that the internal structure, which is visible inside drops ISAMULSION (figa), not visible in the droplets of oil conventional emulsion (fig.7b).

On Fig (a) shows a sample of small-angle scattering of x-rays (SAXS) emulsion ISAMULSION (LPA, with nanostructure), the same as figure 7, and (d) corresponding conventional emulsion (without LPA, without nanostructures), the same as in Fig.7. (b) and (C) correspond to the emulsions ISAMULSION with high oil content and low content of LPA.

Figure 9 shows the small angle x-ray scattering (SAXS) dispersion containing only the LPA, conventional emulsion containing oil (and without LPA) emulsion ISAMULSION, obtained by mixing and homogenization of 60% dispersion LPA and 40% off the regular emulsion.

Figure 10 shows a diagram pseudobinary phase mixture of saturated and unsaturated monoglycerides in the presence of 20% water.

Figure 11 shows a schematic ISAMULSION oil droplets, which contains hydrophilic domains. Note that the hydrophilic domains can be spherical or non-spherical, i.e. in the form of bars, disks, or tubules.

On Fig shows samples of small-angle scattering of x-rays (SAXS) emulsions ISAMULSION containing oil droplets, which have a reversed micellar cubic structure (space group Fd3m).

On Fig-15 shows samples of small-angle scattering of x-rays (SAXS) emulsions ISAMULSION prepared with a mixture of monolinolein (MLO) and diglycerin-monooleate (DGMO) as the LPA.

On Fig shows samples of small-angle scattering of x-rays (SAXS) emulsions ISAMULSION prepared with a mixture of phospholipids (phosphatidylcholine (PC)and monolinolein (MLO) as the LPA.

On Fig shows samples of small-angle scattering of x-rays (SAXS) emulsion ISAMULSION prepared with phosphatidylcholine (PC) as the LPA and triolein as the oil phase. The composition of the emulsion was as follows: 95 wt.% water - 1,912 wt.% triolein - 2,643 wt.% phosphatidylcholine (PC) from oewih beans (Epikuron 200 from Lucas Meyer; LPA) - the 0.375 wt.% Pluronic F127.

On Fig shows samples of small-angle scattering of x-rays (SAXS) emulsion ISAMULSION prepared with phosphatidylcholine (PC) as the LPA and vitamin E as an oil phase. The composition of the emulsion was as follows: 95% of the mass. water - 1,912% of the mass. vitamin E acetate - 2,643% of the mass. phosphatidylcholine (PC) from soybean (Epikuron 200 from Lucas Meyer; LPA) - 0,375% of the mass. Pluronic F127.

Figure 1 shows a typical sequence of structures found within the dispersed droplets of the ISAMULSION oil emulsion, as a function of the content of lipophilic additive in % (% of LPA=α=100·LPA/(LPA + oil)) and temperature. L2 denotes a reversible type structure of the microemulsion; LC indicates the presence of a liquid phase or a mixture of different liquid crystalline phases. As figure 1 shows, a certain self-organizing structure of nanoscale formed at a given temperature and a given amount of added lipophilic additive (value of α) inside drops of oil (for a more detailed description of the mentioned structures, see Evans, D.F.; Wennerström, H. (Eds.); The Colloidal Domain', Wiley-VCH, New York (1999)). The number of added LPA allows you to precisely control the type of self-organization patterns, the amount of water present in the hydrophilic domains, the number of the inner surface of the partition and its size, the self-organizing nanostructures formed inside drops ISAMULSION. In the depending on the type of oil, type of lipophilic additive (LPA) the minimum number of LPA (α), required to initiate the spontaneous formation of self-organizing the internal structure of the droplets ranges from 0.1 to 15 wt.% in terms of the oil phase.

Internal self-organized nanoscale structure of drops of oil in the emulsion can be detected using transmission electron cryo-microscopy or SAXS.

Cryo-THE image in figure 2 obtained using standard techniques Adrian et al. (Adrian et al. Nature, (1984) 308, 32-36). For freezing samples was used homemade guillotine. A drop of the dispersion of the sample, 3 μl was placed on a copper grid covered with a carbon film with holes with a diameter of about 2 μm. To the surface of the grid-side fluid clung filter paper (blotting) to remove excess sample solution. Immediately after removing the fluid mesh is held by tweezers, was set in motion in liquid ethane. Frozen grids were stored in liquid nitrogen and shipped to clouderati, which maintained the temperature of -180°C. Analysis of samples was performed in a Philips CM THOSE at a voltage of 80 kV. In order to minimize losses of the electron beam was applied treatments with low doses. In some cases (7, examples 1, 4 and 5) were used Luggage artisanal production with the maintenance of environmental conditions similar to those described Egelhaaf et al. (Egelhaa et al. J. Microsc. (2000) 200, 128-139). Temperature before dilution and glass formation was set at 25°C, humidity - 100%. ISAMULSION can be identified by the presence of small shiny bumps inside drops of oil. In figure 2, 7a presents obtained using cryo-THOSE micrograph of a typical emulsions ISAMULSION showing the characteristic distance between the brilliant roughness of about 7-8 nm. It should be noted that this kind of gloss unevenness is not found in the standard unstructured emulsions, nor is there and contrasts inside drops unstructured emulsions (fig.7b).

SAXS curves shown in figure 3, obtained using standard equipment (Bergmann et al. J. Appl. Cryst. (2000) 33, 869-875) using x-ray generator (Philips, PW 1730/10), operating at 40 kV and 50 mA with a Cu-anode in the form of a sealed tube. To convert divergent polychromatic x-ray beam in a focused linear beam Cuαradiation (λ=0,154 nm) was used mirror Goebel (Göbel). Sample 2D scattering were recorded on a detector plate with the image and integrated into a one-dimensional scattering function I (q) using the software package SAXSQuant (Anton Paar, Graz, Austria), where q is the length of the scattering vector defined by q=(4π/λ)sinθ/2; λ is the wavelength, and θ is the scattering angle. Broad peaks in the profiles Russ is being "read" by bringing these data in accordance with the generalized indirect method Fourier transform (Bergmann et al. (2000), 33, 1212-1216). Typical distances are d=2π/q. Figure 3 shows samples of small-angle scattering of x-rays emulsion ISAMULSION (the same which was investigated in figure 2) together with the corresponding non-dispersible total oil phase (nanostructured adding LPA), from which it was prepared, and the corresponding conventional emulsion (without LPA, without the nanostructures). You can see that the ISAMULSION shows the same location of the peaks, and non-dispersible total oil phase, from which it was prepared. The characteristic length in the case of both is about 7.5 nm. This characteristic distance greater than the diameter of the hydrophilic domain. Therefore, the hydrophilic domains have a size of less than 7 nm. Qualified in this field specialist such small size of the hydrophilic domains suggests that the internal structure of the oil droplets is thermodynamically stable. Moreover, in the case of the corresponding conventional emulsion in which LPA were added (without CVD), a peak was not observed. This is an additional proof of the presence of nanoscale self-organizing patterns inside drops of oil ISAMULSION. It does not change when the dispersion in water, which indicates that the internal structure of drops ISAMULSION is in a thermodynamic equilibrium state.

Over the CSOs, was not observed changes nanostructures drops ISAMULSION and after a few months of storage of the product (see figure 5), which indicates that thermodynamic equilibrium of internal self-organizing nanoscale structure drops. The reversibility of the process of formation of the internal structure in drops ISAMULSION at heating and cooling (see Fig.6) is another indicator of thermodynamic equilibrium of the resulting nano-sized self-organizing patterns inside drops of oil. Figure 11 shows a schematic representation of a drop of oil, which was nanostructured addition of LPA. Structural characteristics of the hydrophilic domain is figure 11. Hydrophilic domains include polar part (the parent group) LPA (not hydrocarbon tail region and the water part). The minimum diameter of the hydrophilic domain may be approximately 0.5 nm, which is greater than or less than the cross-sectional 2 head groups that do not contain water molecules. The minimum size of the polar part of the lipophilic additive or emulsifier is about 0.2 nm. The diameter of a molecule of water is about 0.3 nm.

Information confirming the possibility of carrying out the invention

Different ways of practical implementation of the present invention provide an emulsion of oil-in-water, in which the dispersed oil droplets show manorism the RNA self-organizing structure of the hydrophilic domain as a consequence of the presence of a lipophilic additive (LPA). The following examples serve only to illustrate the invention and in no way limit the invention, the scope of which is regulated by the attached claims.

Example 1: Typical examples of the emulsion ISAMULSION obtained by homogenizing

In typical cases 1-5 wt.% mineral oils, such as tetradecane, was added to 95 wt.% water already containing the 0.375 wt.% emulsifier (Tween 80 or Pluronic F127 from BASF). Then to the mixture was added 0.5 to 4 wt.% LPA (glycerol monolinoleate). The total number of lipophilic molecules (mineral oil + LPA) was 4,625 wt.%.

This was followed by sonication for 20 minutes. ISAMULSION-th character of the emulsions was confirmed received by cryo-THOSE images and SAXS curves presented in figure 2 and figure 3-4. The results, shown in figure 2, figure 3, figure 5 and 6 were derived from the same characteristic examples of the composition of the 2.4 wt.% mineral oil (tetradecane) - 2.2 wt.% LPA - the 0.375 wt.% primary emulsifier (Pluronic F127) - 95 wt.% water. In addition, were prepared and subjected to the analysis of the corresponding random samples (not dispersed samples containing oil and LPA, but without stabilizer emulsion). The mass ratio of oil (tetradecane)/LPA (glycerol monolinoleate) was 1.1/1.0 in. The mixture of oil-LPA-water was heated and stirred in a Vortex to obtain g is morenogo sample. After addition of 0, 5 or 10 wt.% water to mix oil/LPA sample became transparent, which indicates that the water was completely solubilities in a mixture of oil/LPA and formed a microemulsion In/M After adding high amounts of water sample showed separation. It is noted that the samples containing 15 and 20 wt.% water, gave the same SAXS curves, and the corresponding sample ISAMULSION (2.4 wt.% mineral oil is 2.2 wt.% LPA - the 0.375 wt.% emulsifier). This indicates that the drops ISAMULSION show the same characteristic distance of 7.5 nm, what was observed in the corresponding General phases (see figure 2 and 3). As follows from figure 5, the internal structure of the ISAMULSION is stable for more than 4 months. As is evident from Fig.6, ISAMULSION may heat up and cool down to room temperature, preserving exactly the same internal structure. This indicates that the internal structure of drops of oil ISAMULSION is in thermodynamic equilibrium. Moreover, as follows from figure 4, the emulsion ISAMULSION are formed (for example, you can see the peak on the curve SAXS) already at relatively low concentrations of LPA and high oil content (e.g., 3.9 wt.% mineral oil (tetradecane) - 0,725 wt.% LPA (glycerol monolinoleate) - the 0.375 wt.% emulsifier (Pluronic F127) - 95% water). However ISAMULSION is not formed in the absence of LPA, as shown in figure 3 (composition of 4,625 m is S.% oil (tetradecane), the 0.375 wt.% Pluronic F127, 95 wt.% of water). ISAMULSION is formed also at elevated quantities LPA values (α) (examples of composition: composition 1: 1.32 wt.% tetradecane was 3.3 wt.% LPA - the 0.375 wt.% Pluronic F127; composition 2: a 1.75 wt.% tetradecane - 2.9 wt.% LPA - the 0.375 wt.% Pluronic F127). Structure more ordered than at low value of α (the contents of the LPA), and shows a reversed micellar cubic structure of the hydrophilic domain, which shows SAXS curves (Fig).

Example 2: Typical examples of the emulsion ISAMULSION received hydrotropism by

1 wt.% emulsifier (Pluronic F127) was solubilizers 89 wt.% water to obtain an aqueous solution. 2.5 wt.% mineral oil (tetradecane) and 2.5 wt.% LPA (glycerol monolinoleate) was dissolved in 5 wt.% ethanol with obtaining the lipid solution. The aqueous solution was slowly added to the lipid solution under intensive stirring in a Vortex. By the end of the process spontaneously formed ISAMULSION, i.e. drops with internal self-organizing nanoscale structure.

Example 3: ISAMULSION containing aromatic oil

2 wt.% essential oils (R + lemon) was introduced in 95 wt.% water already containing 0.4 wt.% emulsifier (Pluronic F127). To the mixture was added 2.6 wt.% LPA (glycerol monolinoleate). Was conducted by sonication for 20 minutes. Formed dispersion. As in the case of example 1, SAXS revealed ISAMULSION-th character of the EP emulsion. Education ISAMULSION occurred spontaneously during the stage of processing ultrasound. This example shows that aromatic oils, such as lemon can be used as the oil phase for the formation of ISAMULSION structure.

Example 4: ISAMULSION containing nutrient

2 wt.% oil (d-alpha tocopherylacetate was introduced in 84,625 wt.% water already containing the 0.375 wt.% emulsifier (Pluronic F127) and 10 wt.% maltodextrin. To the mixture was added to 2.5 wt.% LPA (Dimodan U/J (approximately 62% of glycerol monolinoleate, 22% glycerol monooleate, 14% saturated monoglyceride) Danisco, Denmark) and 0.5% ascorbic acid. We then conducted sonication for 2 minutes. As in the case of example 1, SAXS revealed ISAMULSION-th character of the emulsion. The formation of nanoscale self-organizing patterns inside drops of oil occurred during the processing stage of the ultrasound. This ISAMULSION may be spray or freeze-drying to obtain a free flowing powder which can re-dispergirujutsja in the water. This example shows that nourishing oils such as vitamin E, can be used as the oil phase for the formation of ISAMULSION structure.

Example 5: Emulsion ISAMULSION using triglyceride oil

Emulsion ISAMULSION can also be prepared with other oils, for example, with diglyceride or triglidae serednie oils. 0.5 to 4.5 wt.% soybean oil was mixed with 0.5 to 4 wt.% LPA (Dimodan U/J, Danisco, Denmark). This mixture was added to 95% water containing 0,375% emulsifier (Pluronic F127). The total number of lipophilic molecules (oil + LPA) was 4,625 wt.%.

The mixture was subjected to the efforts of the slice transmitter station (Kinematica, Switzerland) for five minutes.

ISAMULSION-th character of the emulsions was confirmed received by cryo-THOSE images (figa), SAXS (figa) and evaluating the corresponding random samples (as was done in example 1). Figa-8A were obtained based on the characteristic examples of the composition of 1,525 wt.% triglyceride oils - 3.1 wt.% LPA - the 0.375 wt.% primary emulsifier (Pluronic F127) - 95 wt.% water. SAXS showed that emulsion ISAMULSION formed also in the reduced content of LPA, for example, when 2,775 wt.% triglyceride oils and 1.85 wt.% LPA in the presence of the 0.375 wt.% primary emulsifier (Pluronic F127) and 95 wt.% water (fig.8b) and 3,2375 wt.% triglyceride oils - 1,3875 wt.% LPA - the 0.375 wt.% primary emulsifier (Pluronic F127) - 95 wt.% water (Fig with). No internal structure was not observed inside drops conventional soybean oil, for example, in the absence of LPA (fig.7b; fig.8d).

Figure 9 presents SAXS curves for 3 different dispersions: (i) a dispersion containing only the LPA and the emulsifier (4,625 wt.% LPA - 0,375% emulsifier - 95% water); (and) conventional emulsion comprising oil and does not contain LPA (4,625 wt.% oil - 0,375%emulsifier - 95% water) and (iii) mixtures of dispersions (i) and (ii), namely: 60% (i) and 40% (ii). The mixture (iii) was mixed in the transmitter station within 5 minutes. SAXS curve for the mixture (iii) (Fig.9) shows that the internal structure of the mixture was very different from the dispersion with LPA (i) and from conventional emulsion (ii) (figa). This indicates that the resulting internal structure of the ISAMULSION drops does not depend on the sequence of mixing and processing.

Example 6: ISAMULSION containing a mixture of 2 LPA, namely: a mixture of saturated and unsaturated monoglycerides

0-1,8 wt.% mineral oil (tetradecane) was added to 0.2-2% of LPA. LPA was a mixture of saturated monoglycerides (Dimodan HR (saturated monoglycerides containing 90% glycerol monostearate), Danisco, Denmark) with unsaturated monoglycerides (Dimodan U/J, Danisco, Denmark). The total number of lipophilic molecules (oil + LPA) was 3%. The mixture was added to 96.7% of water containing 0.3% Tween 80 as emulsifier. Sonication was carried out for 2 minutes. As shown by chart pseudobinary phase, a mixture of saturated monoglyceride (Dimodan HR) with unsaturated monoglyceride (Dimodan U)obtained with 20% water (figure 10), the formation of a stable L2 phase may occur at high temperatures after adding saturated monoglyceride to the sample with unsaturated monoglyceride, which indicates that the emulsion ISAMULSION based on L2 can be formed at you is okeh temperatures. For example, in the case of compositions of 1% tetradecane - 1% saturated monoglycerides - 1% of unsaturated monoglycerides and 0.3% Tween 80 are formed emulsion ISAMULSION, and they are stable at temperatures above 60°C.

Example 7: Emulsion ISAMULSION cooked with monoglyceride (MLO) and diglycerin monooleate (DGMO)

Mixtures containing mineral oil (tetradecane), glycerol-monolinoleate and diglycerin-monooleate (DGMO), was added to 95,375 wt.% water already containing the 0.375 wt.% emulsifier (Pluronic F127). We then conducted sonication for 20 minutes.

SAXS revealed ISAMULSION-th character of the mixtures (Fig-15). Compared with emulsions ISAMULSION, prepared with only the glycerol-monooleate, but without DGMQ (Fig-15), SAXS peaks were shifted towards larger distances, typical use case DGMO that indicates that the hydrophilic domains become larger and that the increased amount of water can solubilisates in droplets in the presence of DGMO. This example shows that mixtures of different LPA can be used to generate characteristic patterns ISAMULSION drops of oil, and that the characteristic size of the hydrophilic domains can be regulated by regulating used LPA.

Example 8: Emulsion ISAMULSION cooked with monoglyceride and phospholipid

Mixtures containing mineral oil (tetradecane), phosphotidyl is in soybean oil (PC) and monolinolein (MLO), added to 95,375 wt.% water already containing the 0.375 wt.% emulsifier (Pluronic F127). We then conducted sonication for 20 minutes.

SAXS revealed ISAMULSION-th character of the mixtures (Fig). This example shows that phospholipids can be used for the formation of characteristic patterns ISAMULSION drops of oil.

Example 9: Solubilization of molecules, which are only moderately soluble in oil at room temperature

A mixture of 1.1 wt.% soybean oil, 0.3 wt.% free phytosterol (ADM, USA) and 1.7 wt.% LPA (Dimodan U) was heated to 130°C to obtain a clear solution. Then it was cooled to 80°C and was added to 0.2% solution of Tween 80 at 80°C. the sonication was carried out for 2 minutes. The dispersion was cooled to room temperature. Method polarized microscopy was not detected in any of the lumps, no (or very little) crystals. Control emulsion system (oil did not contain LPA; 2.8 wt.% soybean oil - 0.31 wt.% the phytosterol - 0.2 wt.% Tween 80) showed a lot of phytosterol crystals having a size in the millimeter range, which was observed under a polarized microscope. This example shows that crystalline lipophilic ingredients or nutrients can solubilisates inside the structure ISAMULSION drops of oil in their molecular form, slowing or preventing their rakista is the implementation.

Example 10: ISAMULSION containing polysaccharides

1.2 wt.% soybean oil is 1.7% Dimodan U (LPA) - 0,0075 wt.% dextran from Fluka (molecular weight 1500 Da) to 0.14 wt.% water is first mixed, then heated and gomogenizirovannykh in the Vortex before the formation of a homogeneous transparent solution. This solution was added to 96,75 wt.% the water in which were dispersed 0.2 wt.% Tween 80. The mixture was treated with ultrasound for 2 minutes. Was obtained ISAMULSION. This example shows that the molecules of the polymers can solubilisates in ISAMULSION.

Example 11: ISAMULSION containing amino acid

of 0.51 wt.% soybean oil - 2,49 wt.% Dimodan U (LPA) - 0.01 wt.% L-leucine - 0.5 wt.% water is first mixed, then heated and gomogenizirovannykh in the Vortex before the formation of a homogeneous transparent solution. This solution was added to 96,29 wt.% the water in which were dispersed 0.2 wt.% Tween 80. The mixture was treated with ultrasound for 2 minutes. Was obtained ISAMULSION.

Example 12: ISAMULSION containing sugar

0.02 wt.% soybean oil - 2.98 wt.% Dimodan U (LPA) - 0.02 wt.% xylose is 0.35 wt.% water is first mixed, then the mixture was heated and was gomogenizirovannykh in the Vortex, and then was cooled to room temperature. This solution was added to 96,43 wt.% the water in which were dispersed 0.2 wt.% Tween 80. The mixture was treated with ultrasound for 2 minutes. Was obtained ISAMULSION. This note is R shows that hydrophilic ingredients can solubilisates in ISAMULSION.

Example 13: ISAMULSION containing antioxidant

of 0.51 wt.% soybean oil - 2,49 wt.% Dimodan U (LPA) - 0.03 wt.% Lyc-O-Mato from Lycored (contains 10% lycopene) were first heated and mixed in a Vortex before the formation of a homogeneous solution. The solution was added to 96,77 wt.% the water in which were dissolved 0.2 wt.% Tween 80. The mixture was treated with ultrasound for 2 minutes. Was obtained ISAMULSION containing lycopene, the solubilized in the inner nanostructure drops of oil. This example shows that lipophilic antioxidants can solubilisates inside the structure ISAMULSION drops of oil, giving a homogeneous emulsion.

Example 14: ISAMULSION using phosphatidylcholine (PC) as the LPA

0,1912 g of triolein - 0,2643 g of phosphatidylcholine (PC) from soybean (Epikuron 200 from Lucas Meyer; LPA) was mixed with 9.5 g of water and 0,0375 g Pluronic F127 (emulsifier), and the mixture was treated with ultrasound for 20 minutes. The emulsion obtained had signs ISAMULSION, i.e. droplets having an internal nanoscale samoorganizovannoe structure, which was formed spontaneously revealed SAXS (see Fig). ISAMULSION could also, if 0,1912 g of vitamin E acetate - 0,2643 g phosphatidylcholine (PC) from soybean (Epikuron 200 from Lucas Meyer; LPA) was mixed with 9.5 g of water and 0,0375 g Pluronic F127 (emulsifier), and the mixture was processed in ultraslo the ohms for 20 minutes (Fig).

Example 15: ISAMULSION using mixtures of phospholipids as LPA and mixtures of different oils

2.2 wt.% phosphatidylcholine from egg yolk, soy beans (Lucas Meyer) was mixed with 2.2 wt.% diolein and 0.6 wt.% tetradecane. This mixture was added to 94,625 wt.% water containing the 0.375 wt.% emulsifier (Pluronic F127). We then conducted sonication for 40 minutes. Was obtained emulsion with typical signs ISAMULSION. PC can also be mixed with phosphatidylethanolamine (PE) or other phospholipid in order to achieve the characteristics ISAMULSION. You can use any combination of different phospholipids and oils to achieve the typical signs ISAMULSION described in this invention.

Example 16: ISAMULSION using phosphoethanolamine (PE) as the LPA and oils

2.2 wt.% 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (AvantiPolar Lipids) were mixed with 0.8 wt.% soybean oil. This mixture was added to 96,7% by weight water containing 0.3 wt.% emulsifier (Pluronic F127). We then conducted sonication for 40 minutes. Was obtained emulsion with typical signs ISAMULSION.

All of these examples, the size of the hydrophilic domains of the dispersed droplets of the emulsion was varied from 0.5 nm to 15 nm.

Emulsion ISAMULSION prepared according to the above examples, can be used as such or as an additive.

After reading Paul is the first description of the invention is skilled in this area specialists clear its practical implementation can be performed within a wide and equivalent range of conditions, compositions and other parameters without prejudice to the scope of the invention or some of its variants.

1. Emulsion oil-in-water for food, cosmetics and pharmaceutical preparations containing dispersed oil droplets having nanoscale samoorganizuyuschejsya structured internal content, including:
(i) an oil selected from the group consisting of mineral oils, hydrocarbons, vegetable oils, waxes, alcohols, fatty acids, mono-, di-, triacylglycerides, essential oils, aromatic oils, lipophilic vitamins, esters, nutraceutical, terpinol, terpenes and mixtures of the above,
(ii) a lipophilic additive (LPA) or mixtures of lipophilic and hydrophilic additives, with the final value of the HLB (figure hydrophilic-lipophilic balance) of less than about 10,
(iii) hydrophilic domains (areas) in the form of drops or tubules containing water or non-aqueous polar liquid, such as a polyol,
and
continuous water phase, which contains the emulsion stabilizers or emulsifiers,
in which oil droplets with a diameter of 5 nanometers (nm) to 900 micrometers (μm) possess self-organizing nanoscale structuring with the formation of the hydrophilic domains have their diameter from 0.5 to 200 nm, due to the presence of lipophilic additives.

2. Emulsion oil-in-water according to claim 1, in which the oil droplets contain soluble in oil, not soluble in oil or water-soluble material selected from the group consisting of fragrances, predecessors, fragrances, medicines, nutraceuticals selected from the group consisting of lutein esters, lutein, β-carotene, tocopherol, tocopherol acetate, tocotrienol, lycopene, Co-Q10oils from flax seed, lipoic acid, vitamin B12, vitamin D, α - and γ-polyunsaturated fatty acids or phytosterols; biologically active additives to food, food additives, plant extracts, medicaments, peptides, proteins or carbohydrates, nutrients, aromatic substances, precursors of aromatic substances.

3. Emulsion oil-in-water according to claim 1, in which the LPA is selected from the group of long chain alcohols, fatty acids, PEG-fatty acid esters of glycerol and fatty acids, monoglycerides, diglycerides, derivatives of mono - and diglycerides, PEG vegetable oils, esters sorbitan, esters of polyoxyethylenesorbitan, mono - and diesters of propylene glycol, phospholipids, phosphatides, cerebrosides, gangliosides, kefallinos, lipids, glycolipids, sulphatides, esters of sugars, simple esters of sugars, esters of sucrose, sterols, with whom you esters of polyglycerol.

4. Emulsion oil-in-water according to claim 3, in which the oil is selected from the group consisting of myristic acid, oleic acid, lauric acid, stearic acid, palmitic acid, PEG 1-4 stearate, PEG 2-4 oleate, PEG-4 dilaurate, PEG-4 dioleate, PEG-4 distearate, PEG-6 dioleate, PEG-6 distearate, PEG-8 dioleate, PEG 3-16 castor oil, PEG 5-10 hydrogenated castor oil, PEG 6-20 corn oil, PEG 6-20 almond oil, PEG-6 olive oil, PEG-6 peanut oil, PEG-6 palm kernel oil, PEG-6 hydrogenated palm kernel oil, PEG-4 capric/Caprylic triglycerides, mono-, di-, tri-, Tetra-esters of vegetable oil and sorbitol, pentaerythritol di-, Tetra-stearate, isostearate, oleate, kaprilat or caprate, polyglyceryl-3-dioleate, -stearate or-isostearate, polyglyceryl 4-10 pentolate, polyglyceryl 2-4 oleate, -stearate or-isostearate, polyglyceryl-6 dioleate, polyglyceryl-10 trioleate, polyglyceryl-3 distearate, mono- or diesters of propylene glycol and fatty acids6-C20, monoglycerides of fatty acids With6-C20derived lactic acid and monoglycerides, derivatives of lactic acid and diglycerides, dietilovogo of ester of tartaric acid and monoglycerides, triglycerin-monostearate-cholesterol, phytosterol, PEG 5-20 soy Sterol, PEG-6 sorbitan Tetra-, exactearth, PEG-6 is orbital of tetrazolate, sorbitan of monolaurate, sorbitan of monopalmitate, sorbitan mono - and trioleate, sorbitan mono - and tristearate, sorbitan of monoisostearate, sorbitan of sesquioleate, sorbitan of sesquistearate, PEG 2-5 olejowego simple ether, PEG 2-4 lauric simple ether, PEG-2 cetyl simple ether, PEG-2 stearyl simple ether, distearate sucrose, dipalmitate sucrose, ethyloleate, isopropylmyristate, isopropylpalmitate, ethyllinoleate, isopropylmalate, poloxamers, phospholipids, lecithins, kefallinos, oat lipids and lipophilic amphiphilic lipids of other plants and mixtures of the above.

5. Emulsion oil-in-water according to claim 1, in which the stabilizer or emulsifier selected from the group consisting of low molecular weight surfactants having HLB>8, milk proteins or soy peptides, protein hydrolysates, block copolymers, surface active hydrocolloids such as gum Arabic, xanthan gum.

6. Emulsion oil-in-water according to any one of claims 1 to 5, in which the emulsion is in the form of powder.

7. Emulsion oil-in-water according to any one of claims 1 to 5, in which the emulsion is prepared product.

8. Emulsion oil-in-water according to any one of claims 1 to 5, in which the emulsion is a starting material, intermediate product or an additive to the finished product.



 

Same patents:

FIELD: industrial biotechnology; methods of production of the microcapsules.

SUBSTANCE: the invention is pertaining to the industrial biotechnology and is intended for production of the micro-capsulated biopreparations of the natural compounds. The purpose of the invention is development of the effective method of production of the microcapsules of the liquid-phase natural substances. The method is exercised by the emulsification of the encapsulated substance in the polymer solution and sedimentation of the polymer on the surface of the emulsion drips. The sedimentation(is conducted three times at the temperature of 75-80°C during 5-10 minutes at the continuous stirring with the subsequent treatment with the acetone In the capacity of the polymer solution use 1-2.5 % solution of methyl cellulose with the content of the metoxyl groups from 27.5 up to 32 %. In the capacity of the emulsifier use the rape oil in amount of 7.5-40 mass % from the amount of the polymer solution.

EFFECT: the invention ensures development of the effective method of production of the microcapsules of the liquid-phase natural substances.

4 cl, 4 ex

FIELD: colloid chemistry.

SUBSTANCE: method comprises dispersing water emulsion of hydrophobic polymer in a liquid immiscible with water containing emulsifier, producing the emulsion with enriched phase that comprises water dispersed phase containing the hydrophobic polymer, and inducing inter-phase reaction of polycondensation at least of one of the reagents of the inter-phase polycondensation to produce polymeric film around the hydrophobic polymer.

EFFECT: enhanced efficiency.

40 cl, 5 ex

The invention relates to a method of encapsulation of pesticide

The invention relates to microparticles having improved stability during storage, and to a process for the preparation of such microparticles

The invention relates to the field of microcapsulation, in particular to the microencapsulation of liquid-phase materials with limited solubility in water

The invention relates to the production of microcapsules, the core of which is a liquid-phase material with limited solubility in water

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and pharmaceutical industry, namely to method of obtaining poly-DL-lactide-co-glycolide nanoparticles with antituberculosis medications, incapsulated in them, which includes: obtaining lyophilised particles of stable medications, including: stage 1: obtaining lyophilised particles of stable medications, including: stage 2: obtaining lyophilised particles of unstable medications, including: stage 3 combination of lyophilised particles obtained at stages 1 and 2 with obtaining said composition.

EFFECT: claimed is method of obtaining novel nanoparticles.

14 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and concerns composition, which stimulates immune answer, containing nanoparticles, based on copolymer of methylvinyl ether of maleic anhydride. Mentioned nanoparticles can additionally contain allergen or antigen and/or immunostimulating agent, which can be inside of said nanoparticles and/or at least partially cover surface of mentioned nanoparticles and optionally crossing-linking agent. Composition, which stimulates immune response, can be applied as adjuvant in immunotherapy and vaccines.

EFFECT: increase of activity.

32 cl, 7 ex, 2 tbl, 13 dwg

FIELD: medicine.

SUBSTANCE: at first component microspherolites of carbonates of alkaline earth metals and encapsulatable protein are prepared, then capsules are made by sequential adsorption into composite microsperolites of oppositely charged polyelectrolytes to be preselected by sequential examination of each polyelectrolyte effect on encapulatable protein in the solution. The carbonates of alkaline earth metals are removed from capsules by means of EDTA or another chelating agent or by means of acidification. Polyelectrolytes are taken as biodegradable biodegradation deficient complex cations and polyanious of predominantly linear structure. After absorption of required quantity of polyelectrolyte layers the protein activity shall be controlled.

EFFECT: retention of functional properties of protein during its encapsulation.

6 cl, 2 ex, 5 dwg

FIELD: medicine.

SUBSTANCE: invention concerns oncological area of medicine (along with genetic engineering and biochemistry) and methods of obtaining magnetosensitive liposome systems of medication delivery with controlled release. Method of obtaining magnetosensitive liposomes carrying medication involves dissolution of phospholipids in chloroform, addition of magnetic effect carrier and ultrasonic processing. Badger's fat is used as phospholipid source, ferromagnetic metal nanopowder with 2-5 nm particle size, obtained by gas phase method, is used as magnetic effect carrier and coated with carbon shell, and liposome system is sterilised in betatron chamber.

EFFECT: novel method of magnetosensitive liposome obtainment.

2 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: invention relates to topical formulation with: spironolactone nanoparticles, containing medium-diameter nanoparticles measured by photonic correlation spectroscopy technique, in the range approximately 300 nm to 900 nm, and dispersion of solid polar lipids crystals in polar liquid, with additional stabiliser. The nanoparticles are included in crystal structure formed by solid polar lipids crystals; the lipids mentioned being directed their hydrophilic ends outside, and hydrophobic ends inside, relative to spironolactone nanoparticles. Items of the patent application are also as follows: method of producing the formulation, the crystal lattice arrangement of solid polar lipids crystals with spironolactone nanoparticles included, and use of the nanosuspension with structure mentioned for medication producing, intended for therapy in anti-androgen responding conditions.

EFFECT: achieving of high stability formulation and increased bioavailability of spironolactone.

17 cl, 4 ex, 8 tbl, 11 dwg

FIELD: medicine.

SUBSTANCE: means has micro-particles of practically pure active substance immersed into biologically compatible pharmacologically permissible polymer. The polymer is ester of polyol and copolymer of polylactide and glycolide. The polyol has at least three hydroxide groups and molecular weight not greater than 20000.

EFFECT: enhanced effectiveness in introducing drug as depot; supporting therapeutically effective dose of active substance.

9 cl, 1 tbl

FIELD: chemistry of polymers, medicine.

SUBSTANCE: invention describes a micelle-formed composition including hydrophobic core covered by hydrophilic envelope and a therapeutic agent as a component of micelle said wherein hydrophobic core is chosen from group consisting of poly-(ortho-ester), polyanhydride, pseudopoly-(amino acid) prepared from tyrosine, polyphosphazene or poly-(β-benzyl-L-aspartate) and their combinations, or polyester chosen from group consisting of poly-(glycolic acid), poly-(lactic acid), poly-(D-lactic acid), poly-(D,L)-lactic acid), copolymers of lactide/glycolide, polycaprolactone and their derivatives and wherein hydrophilic envelope represents poly-(N-vinyl-2-pyrrolidone). Indicated composition can be easily dispersed or dissolved repeatedly after addition of water or aqueous solution to a form obtained after sublimation drying the indicated micelle-formed composition. Using hydrophilic envelope allows avoiding aggregation of micelles. Also, invention provides simplifying stages in preparing micelles.

EFFECT: improved and simplified preparing method.

10 cl, 4 tbl, 1 ex

FIELD: medicine, biochemistry, pharmacy, biotechnology.

SUBSTANCE: invention relates to a method for preparing polyelectrolyte microparticles containing the end substance and showing sensitivity to alteration of the environment composition. Method involves preparing oppositely charged polyelectrolytes on microaggregates containing an encapsulated substance. These polyelectrolyte microparticles can be used both in medicine as systems used in delivery drugs and providing pH-sensitive release of encapsulated substance and in biotechnology as biocatalysts stabilized with respect to unfavorable conditions. Invention provides preparing polyelectrolyte microparticles characterizing by the high content of active substance - up to 90% of microparticles mass. Proposed method is sample and involves lesser amounts of steps.

EFFECT: improved preparing method.

9 cl, 3 tbl, 2 dwg, 61 ex

The invention relates to a pharmacy and concerns microspheres

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention refers to chemical-pharmaceutical industry, and concerns an emulsion of perfluororganic compounds (PFOC) for medicine and biology, containing mixed perfluorocarbons (PFC) with a main ingredient being perfluorodecahydronaphthalene (PFD) and mixed perfluorochemical tertiary amines (PFTA) with a main ingredient being perfluoro-N-(4-methylcyclohexyl)-piperidine (PFMCP), having smaller excretion rates than PFD, a stabilising agent and a physiologically acceptable water-salt solution with energy metabolism substrata, differing that all the ingredients of PFOS have critical hexane solution temperatures (TcrH), differing no more than by 2-4°C, and the stabilising agent represents mixed block copolymers from the group of block copolymers polyoxyethylene-polyoxypropylene with an average weight content of polyoxypropylene 20%. The invention also concerns a method for making said emulsion, and a method of treating with applying the declared emulsion.

EFFECT: prepared emulsions show high stability and are non-toxic.

21 cl, 5 tbl, 17 ex, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and concerns a pharmaceutical composition containing ivermectin in the form of cream gel, including in a physiologically comprehensible medium an oil phase, dispersed in an aqueous phase with a polymer emulsifier which is not a surfactant, and said oil phase contains oils of fusion temperature lower than 30°C and are free from hard fats of fusion temperature higher than 30°C.

EFFECT: making the composition for the pharmaceutical preparation for treating dermatological conditions, particularly acne rosacea.

20 cl, 11 ex, 6 tbl

FIELD: medicine.

SUBSTANCE: invention concerns an anhydrous aerosol composition containing a combination of clobetasol propionate and calcitriol as an active pharmaceutical ingredient, an alcoholic phase and an oil phase in a physiologically acceptable medium, and relates to its application in cosmetology and dermatology.

EFFECT: increased efficiency of the composition.

9 cl, 18 ex, 24 tbl

FIELD: veterinary science.

SUBSTANCE: agent contains sapropelic composition, emulsifier OP-10 and water at the following ratio of components, wt %: sapropelic composition 20-60; emulsifier OP-10 5-15; distilled water - the rest.

EFFECT: improvement of medical effect, simplified application, production of agent does not require high financial and time expenditures.

2 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical industry and concerns galenicals that ensure to improve intestinal absorption of the oral agents; to the method of making thereof, and also to application if lipid excipients combined with one or more surface-active substances for inhibition of an efflux pump.

EFFECT: invention allows improving intestinal absorption of the oral agents.

34 cl, 2 ex, 4 tbl, 5 dwg

Up!