WO2004080582A2

WO2004080582A2 - Ester polyols as solvents, and emulsions and dispersions containing the same

Info

Publication number: WO2004080582A2
Application number: PCT/EP2004/002385
Authority: WO
Inventors: Stefan Günter BORCHERT; Gerd Dahms; Rolf-Dieter Petersen
Original assignee: Clr-Chemisches Laboratorium Dr. Kurt Richter Gmbh
Priority date: 2003-03-11
Filing date: 2004-03-08
Publication date: 2004-09-23
Also published as: WO2004080582A3; DE10310523A1

Abstract

The invention relates to ester polyols which are derived from glycerine, C2-20-alkylene glycol, poly(C2-20-alkylene)glycol, ethylene glycol, polyethylene glycol, preferably in which up to 30 % of the ethyleneoxy units can be replaced by propyleneoxy units, polyglycerines, sorbitol and pentaerythritol, as polyol constituents, and aliphatic C3-6-carboxylic acids, as acid constituents, which, in addition to a carboxyl group, comprise at least one other functional group selected from hydroxyl and carboxyl groups; or mixtures of the ester polyols with aminofunctional polyols having a melting point lower than 100 °C; or ester polyols of general formula (I): R1-O-[EO-]n[PO-]mR2 wherein R1 represents C1-4-alkyl, R2 represents hydrogen or C1-4-alkyl, n represents on average between 1 and 100, m represents on average between 0 and n/2, and EO and PO represent base units which are derived from ethylene oxide and propylene oxide and can be in any sequence when both base units are present. According to the invention, said ester polyols can be used as solvents, solubilisers, or dispersants for organic compounds which are insufficiently soluble or insoluble in lipophile and hydrophile media, for pharmaceutical, cosmetic, washing agent, food, or agrarian active ingredients, and as dispersants or continuous phases for (micro)pigment dispersions.

Description

Ester polyols as solvents and emulsions and dispersions containing them

The invention relates to the use of este polyols as solvents or solubilizers for organic compounds which are insufficiently soluble or insoluble in lipophilic and hydrophilic media and as dispersants for (micro) pigments. The invention further relates to este polyol / polyol-in-oil emulsions (EP / O emulsions) containing este polyols, processes for their preparation, ester polyol / polyol-in oil in water emulsions (EP / O / W) containing these emulsions Emulsions), their

Use in cosmetic and / or pharmaceutical and / or detergent technology and / or food technology and / or agricultural technology active ingredient compositions and compositions of this type.

In cosmetic and / or pharmaceutical and / or agro-active ingredient compositions, emulsions with active ingredients are often used, with which suitable compositions can be produced for the desired form of use. The production of polyol-in-oil emulsions and polyol-in-oil-in-water emulsions is known per se. Such emulsions can be used to convert cosmetic and / or pharmaceutical active ingredients into a form suitable for use. DE-A-43 41 114 relates to anhydrous X / O emulsions which contain a non-aqueous, oil-immiscible phase and an oil phase. 1 h of the non-aqueous, oil-immiscible phase, an active ingredient, which can also be in the form of a solid, can be present for medical, cosmetic or technical applications, for example. The emulsion is made using a special emulsifier that has a maximum HLB of 6 or is a W / O emulsifier. Propylene glycol, butylene glycol, polyalkylene glycol, glycerin, polyglycerol and mixtures thereof are mentioned as usable polyol.

DE-A-43 41 113 relates to a stable multiple emulsion of the X / O / Y type. X is an oil-immiscible component, O an oil phase and Y an aqueous phase. W / O / W emulsions and P / O / W emulsions are described in particular, it being possible in turn to use propylene glycol, butylene glycol, polyalkylene glycol, glycerin, polyglycerol or mixtures thereof as the polyol phase.

Many cosmetic or pharmaceutical or agro active ingredients are not soluble in hydrophilic and lipophilic media. In particular, they are not soluble in water or oil. Such active substances can therefore often only be applied in the form of finely divided dispersions of the solids in carrier media, which leads to disadvantages in terms of formulation, dosage and use. The presence of solids results in complex formulations of the cosmetic or pharmaceutical compositions. In addition, active ingredients can often not be used in a suitable form for an application.

The object of the present invention is to provide cosmetically, pharmaceutically and agrotechnologically compatible solubilizers for active ingredients which are insufficiently soluble or insoluble in hydrophilic and lipophilic media. Furthermore, polyol-in-oil emulsions are to be provided with a novel polyol substitute component, the substitute component being able to act as a solubilizer for the active ingredients. The aim is to remedy the disadvantages of the known active substance formulations. Alternative solid lipid nanoparticle (SLN) systems are also to be made available.

The object is achieved by the use of ester polyols, which differ from

Glycerol, C _2-20 alkylene glycol, preferably C _-10 alkylene glycol, especially C _2-8 alkylene glycol, for example propylene glycol, butylene glycol and especially ethylene glycol, poly (C _2-20 alkylene) glycol, preferably poly (C _{2- 10-} alkylene) glycol, in particular poly (C _2- ₈ alkylene) glycol, with one or more different alkylene radicals, for example polyethylene glycol, in which up to 30% of the ethyleneoxy units can be replaced by propyleneoxy units, polyglycerols, sorbitol, pentaerythritol as the polyol component and

aliphatic C _3-6 carboxylic acids which, in addition to a carboxyl group, have at least one further functional group selected from hydroxyl and carboxyl groups, as the acid component

derive, or mixtures of the este polyols with uri-functional polyols with a melting point of less than 100 ° C or este polyols of the general formula (I) R'-O-IΈO-PO- R ²

(I)

with the meaning

R ¹ -C _-4 alkyl,

R is hydrogen or C _1-4 alkyl, n on average 1 to 100, m on average 0 to n / 2

EO, PO basic building blocks derived from ethylene oxide and propylene oxide, which can exist in any order if both basic building blocks are present,

as a solvent, solubilizer or dispersion aid for organic compounds which are insufficiently soluble or insoluble in lipophilic and hydrophilic media, pharmaceutical, cosmetic, detergent technology, food technology or agricultural technology active ingredients and as a dispersion aid or continuous phase for (micro) pigment dispersions.

The este polyols which are used according to the invention are derived from polyol components and acid components which are esterified with one another. Glycerol, ethylene glycol, polyethylene glycol, in which up to 30% of the ethyleneoxy units can be replaced by propyleneoxy units, and mixtures thereof are used as the polyol component. The polyethylene glycol preferably contains 1 to 600, particularly preferably 1 to 100, ethyleneoxy units.

Aliphatic C _3-6 carboxylic acids are used as the acid component which, in addition to a carboxyl group, have at least one further functional group selected from hydroxyl and carboxyl groups. The carboxylic acids preferably contain only carbon, hydrogen and oxygen as atoms. The carbon chain can be free of double bonds or contain a double bond. Examples of suitable acid components are lactic acid, maleic acid, tartaric acid and citric acid.

One, two, three or more, for example all, hydroxyl groups of the polyol component may be esterified in the este polyols. Likewise, one, two, more or all of the carboxyl groups of the acid component can be in ester form. The este polyols used according to the invention can be in solid, glass-like, viscous or liquid form at room temperature (25 ° C.). The properties can be specifically adjusted by mixing several este polyols. For example, lactates are usually in liquid form, while citrates are in a glass-like state and only become viscous at a temperature of around 50 ° C. A 1: 1 mixture of citrate and lactate is similar to glass. In contrast, a mixture of citrate and lactate in a weight ratio of 1: 2 is viscous. The este polyols are often crystal clear and solid at room temperature.

The este polyols can be used in combination with amino-functional polyols, ether alcohols or both compounds. The proportion of este polyols in such mixtures is preferably at least 10% by weight, particularly preferably at least 15% by weight, in particular at least 20% by weight.

Any suitable amino-functional polyol which has a melting point of less than 100 ° C., preferably less than 50 ° C., can be used as the amino-functional polyol. The term "amino-functional" polyols means that there is at least one amine group or amide group in the polyol. The polyol also has at least two hydroxyl groups. It can be an aliphatic, aromatic or aromatic / aliphatic polyol. It is preferably an aliphatic polyol. The polyol particularly preferably contains 2 to 10, particularly preferably 2 to 5, in particular 2 to 3, hydroxyl groups. In addition to the functional groups mentioned, the amino-functional polyols can have carbonyl groups, carboxyl groups, thiol groups and carbon-carbon double bonds or triple bonds. They can also have ether groups. Some of the hydroxyl groups present in the molecule can be etherified, provided that at least two free hydroxyl groups are present in the molecule. The amino-functional polyols used according to the invention preferably contain one or two amide groups.

According to the invention, it is preferred to use amino-functional polyols which have two or three hydroxyl groups and one or two amide groups. They can also have an additional thiol group or carboxyl group. The compounds preferably contain 5 to 15 carbon atoms, particularly preferably 7 to 12 carbon atoms.

The amino-functional polyol is preferably a pantothene derivative of the general formula (II) HO-CH ₂ -C (CH ₃ ) ₂ -CH (OH) -CO-NH-CH ₂ -CH ₂ -R

(II)

with R COOK ¹ , CH OR ¹ , CO-NH-CH2-CH ₂ -SR ¹

R ¹ H, Ci.u-Al yl, phenyl.

R is preferably a CH ₂ -OR ¹ radical. R ¹ is preferably hydrogen or C _1-6 alkyl, in particular hydrogen or C _1-3 alkyl.

Pantothenic acid, panthenol or panthetein are particularly preferably used. The pantothene derivatives are preferably in the (R) form. Pantothenic acid can also be used in the form of the salts, the pantothen derivative (R) - panthenol being particularly preferred.

The compounds preferably used according to the invention have a molecular segment which is derived from pantoic acid, and a molecular segment which is derived from β-alanine, provided that it is a compound comparable to pantothenic acid.

Panthenol and pantothenic acid are known from the medical field for wound healing as well as from hair treatment agents and feed additives. The preparation can be carried out via biosynthesis from 2-oxo-3-methylbutanoic acid or from pantolactone. Other manufacturing processes are generally known. Reference can also be made to Beilstein EIV 4, 2571, Beilstein EV 18/1, 22 and Beilstein E IV 4, 2569f and Isler et al., Vitamine II, pages 309 to 339, Thieme-Verlag, Stuttgart, 1988. There is also extensive patent literature dealing with the use of pantothen derivatives, in particular panthenol, in cosmetic and pharmaceutical compositions.

Basic building blocks derived from ethylene oxide and optionally additionally from propylene oxide can be present in the este polyols of the general formula (I). These basic building blocks have the structures -CH ₂ -CH ₂ -O-, -CH ₂ -CH (CH ₃ ) -O- and -CH (CH ₃ ) - CH ₂ -O-. If the two basic building blocks derived from ethylene oxide and propylene oxide are present, they can be in any order. This means that one or more blocks derived from ethylene oxide and propylene oxide can be connected to one another. The units derived from ethylene oxide and propylene oxide can also be present alternately or statistically. The continuous transitions possible between these forms are also possible according to the invention. In the general formula (I), the proportion of the basic building blocks derived from propylene oxide is at most a fraction of the amount of basic building blocks derived from ethylene oxide. While on average 1 to 100, preferably 2 to 70, particularly preferably 3 to 50, in particular 5 to 15, of ethylene oxide derived basic building blocks are present, there are 0 to n 2, preferably 0 to n / 4, particularly preferably 0 to n / 8 basic building blocks derived from propylene oxide. If basic building blocks derived from propylene oxide are present, their amount is preferably n / 10 to n / 4, particularly preferably n / 8 to n / 5. The numbers n and m are average values, since the alkoxylation range generally results in a distribution of the degree of alkoxylation. Therefore, odd-numbered values for n and m are also possible. The breadth of the distribution of the degree of alkoxylation also depends, inter alia, on the alkoxylation catalyst used. It is also possible to set discrete degrees of alkoxylation or very narrow distributions of the degree of alkoxylation.

R ¹ is a C _1-4 alkyl radical, preferably C _1-3 alkyl radical, particularly preferably C _1- alkyl radical, in particular a methyl radical. Propyl residues include n-propyl and iso-propyl, while butyl residues include n-butyl, iso-butyl, tert-butyl.

1

R represents hydrogen or a radical as defined for R above. The meaning of R ^{2 is} independent of the meaning of the radical R ¹ . R ² is particularly preferably hydrogen. The term "Estolyol" used in the description and the claims includes all compounds of the general formula (I), ie also the cases in which R ^{2 is} not a hydrogen atom and thus there are no free hydroxyl groups in the molecule.

The este polyol is preferably a methanol ethoxylate with 5 to 15 ethylene oxide units.

Polyethylene glycol monomethyl ether (12EO) and polyethylene glycol monomethyl ether (7EO) are particularly preferably used. These are pure methyl alcohol ethoxylates. Such compounds are known per se and have hitherto been used for the preparation of methyl end groups

Fatty acid polyethylene glycol esters used. The connections are commercially available.

According to the invention, particular preference is given to using este polyols of the general formula (I) which are liquid at room temperature (25 ° C.). The expression "Esteφolyol / Polyol" as used to describe Esteφθlyol / Polyol-in-Oil Emulsions (EP / O), Esteφolyol / Polyol phases and Esteφolyol / Polyol-in-Oil-in-Water Emulsions (EP / O / W) is used, indicates that an Esteφolyolphase or a mixed Esteφolyol / Polyol phase can be present. The corresponding carrier phase is thus either formed only by the ester polyols of the general formula (I), or there are mixtures of the ester polyols with polyols, ether alcohols or amino-functional polyols. In addition, as described below, organic or inorganic compounds may be present in the ester polyol / polyol phase.

One or more este polyol / polyol phases can be present in the este polyol / polyol-in-oil emulsions (EP / O emulsions) according to the invention. Preferably there is an este polyol / polyol phase which contains at least one este polyol as described above. At least 10 or at least 50% by weight, particularly preferably at least 80% by weight, in particular at least 95% by weight, of the este polyol are preferably present in the polyol phase, based on the total este polyol / polyol phase. - In the este polyol / polyol phase water may also be present in an amount of at most 20% by weight, preferably at most 10% by weight, in particular at most 5% by weight, based on the total estepolyol / polyol phase. The este polyol / polyol phase is preferably largely or completely anhydrous. The sum of este polyol, optionally ether alcohol, amino-functional polyol, other polyol and water is 100% by weight.

The customary known polyols such as propylene glycol, butylene glycol, ethylene glycol, polyalkylene glycol, glycerol, polyglycerol, glycosides, sorbitol, mannitol, pentaerythritol, trimethylolpropane or mixtures thereof can be present as polyols. Polyalkylene glycols in particular include polyethylene glycol and polypropylene glycol. Other suitable polyols are known to the person skilled in the art, for example aromatic polyols such as Emodin / Aloe Vera. These polyols can also be the basis of the above este polyols.

Particularly preferably, only esteolyols as described above are present in the estepholyol / polyol phase.

According to the invention, the este polyol / polyol phase is not miscible with oil. This means that when the EP / O emulsions according to the invention are produced, preferably no estepolyol / polyol dissolves in the oil phase or oil dissolves in the estepolyol / polyol phase. Minor deviations from this (about up to 5% by weight, preferably up to about 1% by weight, in particular up to about 0.5% by weight of solubility) are irrelevant here. It depends on the fact that in the EP / O emulsion an emulsion of the este polyol / polyol phase is obtained in the oil phase and not a solution of the este polyol / polyol in the oil.

All known suitable oils and their mixtures can be used as oil in the oil phase. Examples of suitable oils are silicone oils and derivatives thereof, which can be linear or cyclic, natural ester oils such as grape seed oil, olive oil or sunflower oil, synthetic ester oils such as neutral oils, which can be linear or branched, paraffin oils and isoparaffin oils, ester oils, for example the citrates, lactates, aleates , Salicylates, cinnamates or other organic light protection filters, or of camphor derivatives, triglycerides, fatty alcohols or mixtures thereof.

In the EP / O emulsions, the weight ratio of estepolyol / polyol phase to oil phase is preferably 10:90 to 90:10, particularly preferably 25:75 to 75:25 and in particular 40:60 to 60:40.

Any suitable emulsifiers which are suitable for producing an emulsion of the este polyol / polyols in oil can be used as emulsifiers. Examples of suitable emulsifiers are glycerol esters, polyglycerol esters, sorbitan esters, sorbitol esters, fatty alcohols, propylene glycol esters, alkyl glucose esters, sugar esters, lecithin, silicone copolymers, wool wax and mixtures or derivatives thereof. Glycerol esters, polyglycerol esters, alkoxylates and fatty alcohols and iso alcohols can be derived, for example, from castor fatty acid, 12-hydroxystearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, stearic acid, myristic acid, lauric acid and capric acid. In addition to the esters mentioned, succinates, amides or ethanolamides of the fatty acids can also be present. Suitable fatty acid alkoxylates are, in particular, the ethoxylates, propoxylates or mixed ethoxylates / propoxylates.

The amount of emulsifier can be adapted to practical requirements. The emulsifier is preferably used in an amount of 0.1 to 20% by weight, particularly preferably 0.5 to 15% by weight, in particular 1 to 8% by weight, based on the entire EP / O emulsion , In some cases, different doses may be necessary.

According to one embodiment of the invention, the este polyol / polyol phase or the este polyol solution or dispersion can contain a cosmetic and / or pharmaceutical active ingredient or perfume, perfume oils or aromas dissolved in the phase. It can also be a detergent technology, food technology technology or agricultural technology (agro) active ingredient. The active substances are preferably organic compounds which are insufficiently soluble, in particular insoluble, in lipophilic and hydrophilic media. The compounds are insufficiently soluble or insoluble, especially in water and oil. Any suitable active ingredients can be used, provided they dissolve in the este polyol or the este polyol / polyol phase containing the este polyol. Suitable active ingredients are, for example, dichlophenac, ibuprofen, acetylsalicylic acid, salicylic acid, erythromycin, ketoprofen, cortisone, glucocorticoids.

Also suitable are cosmetic active ingredients that are particularly sensitive to oxidation or hydrolysis, such as polyphenols. Catechins (such as epicatechin, epicatechin-3-gallate, epigallocatechin, epigallocatechin-3-gallate), flavonoids (such as luteolin, apigenin, rutin, quercitin, fisetin, kaempherol, rhametin), isoflavones (such as genistein, glycine, daidzein) Prunetin), coumarins (such as daphnetin, umbelliferon), Emodin, Resveratrol, Oregonin.

Vitamins such as retinol, tocopherol, ascorbic acid, riboflavin, pyridoxine are suitable.

Also suitable are total extracts from plants that include contain the above molecules or classes of molecules.

According to one embodiment of the invention, the active ingredients are light protection filters. These can be in the form of organic light protection filters at room temperature (25 ° C) in liquid or solid form. Suitable light protection filters (UV filters) are, for example, compounds based on benzophenone, diphenyl cyanoacrylate or p-aminobenzoic acid. Specific examples are (INCI or CTFA names) Benzophenone-3, Benzophenone-4, Benzophenone-2, Benzophenone-6, Benzophenone-9, Benzophenone-1, Benzophenone-11, Etocrylene, Octocrylene, PEG-25 PABA, Phenylbenzimidazole Sulfonic Acid, ethylhexyl methoxycinnamate, ethylhexyl dimethyl PABA, 4-methylbenzylidene camphor, butyl methoxydibenzoylmethane, ethylhexyl salicylate, homosalate and methylene-bis-benzotriazolyl tetramethylbutylphenol (2,2'-methylene-bis- {6- (2H-2-benzol) -4- (1, 1, 3, 3 -tetramethylbutyl) phenol}, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and 2,4,6-trianilino-p- (carbo-2'-ethylhexyl-1 ' -oxi) - 1, 3, 5-triazine.

Other organic light protection filters are octyl triazone, avobe zone, octyl methoxy cinnamate, octyl salicylate, benzotriazole and triazine. The este polyols can also be used as solubilizers and / or dispersants for antidandruff agents.

According to a further embodiment of the invention, anti-dandruff active ingredients such as are usually present in cosmetic or pharmaceutical formulations are used as active ingredients. An example of this is piroctone olamine (1-hydroxy-4-methyl-6- (2,4,4-dimethylpentyl) -2 (1H) -pyridone; preferably in combination with 2-aminoethanol (1: 1)). Other suitable agents for the treatment of skin flakes are known to the person skilled in the art.

According to a further embodiment of the invention, organic dyes are used as active substances or instead of active substances.

Any suitable amounts of the active ingredient can be introduced into the ester polyol / polyol phase. The amount that can be introduced is often determined by the solubility and the ultimate field of application of the preparation. As a rule, 0.01 to 95% by weight, preferably 0.1 to 80% by weight, in particular 2 to 50% by weight, of the active ingredient are introduced into the estepolyol or the estepolyol / polyol phase, the proportion by weight refers to the sum of active ingredient and este polyol / polyol. In other words, in the amount of estepolyol / polyol phase stated above, the stated proportion by weight of estepolyol / polyol can be replaced by the active ingredient. For example, based on the pure este polyol / polyol phase, 0.01 to 95% by weight of the este polyol / polyol phase can be replaced by the active ingredient. This means that the above statements regarding the proportion of the este polyol / polyol phase in the emulsion remain applicable. The content of Esteφolyol / Polyol or Esteφolyol then just decreases by the proportion of active ingredient which is then present in the Esteφolyol / Polyolphase.

It is also possible to fill a conventional carrier system for the active ingredient with the este polyol in order to arrive at the este polyol / polyol phase mentioned.

The EP / O emulsion or dispersion described above can also be emulsified in water or a water-in-oil emulsion. The result is an este polyol / polyol in oil in water emulsion (EP / O / W emulsion) which contains at least one emulsion as described above and additionally at least one aqueous phase. The structure of such multiple emulsions can correspond to the emulsions described in DE-A-43 41 113, the polyol component being varied in the manner according to the invention. The structure of the Esteφolyol / polyol-in-oil emulsion can be the structure of the in DE-A-43 41 114 correspond to the emulsions described, the este polyol / polyol phase according to the invention being used as the polyol phase.

When the EP / O emulsion according to the invention is introduced into water or aqueous systems, the weight ratio of the individual phases can be varied within wide ranges. In the EP / O / W emulsion ultimately obtained, the weight fraction of the EP / O emulsion is preferably 0.01 to 80% by weight, particularly preferably 0.1 to 70% by weight, in particular 1 to 30% by weight. %, based on the total EP / O / W emulsion.

When the EP / O emulsion according to the invention is introduced into an O / W emulsion, the proportion of the EP / O emulsion is preferably 0.01 to 60% by weight, particularly preferably 0.1 to 40% by weight, in particular 1 up to 30% by weight, based on the EP / O / W emulsion ultimately obtained. 3 hours of the O / W emulsion used for this purpose, the oil content is preferably 1 to 80% by weight, particularly preferably 1 to 30% by weight, based on the O / W emulsion used.

The individual phases of the emulsions can also have the usual ingredients known for the individual phases. For example, the individual phases can contain further pharmaceutical or cosmetic active ingredients that are soluble in these phases. The aqueous phase can contain, for example, organic soluble light protection filters, hydrophilically coated micropigment, electrolytes, alcohols, etc. Some or all of the phases can also contain solids, which are preferably selected from pigments or micropigments, microspheres, silica gel and similar substances. The oil phase can contain, for example, organically modified clay minerals, hydrophobically coated (micro) pigments, organic oil-soluble light protection filters, oil-soluble cosmetic active ingredients, waxes, metal soaps such as magnesium stearate, petroleum jelly or mixtures thereof. Titanium dioxide, zinc oxide and barium sulfate, as well as wollastonite, kaolin, talc, Al ₂ O ₃ , bisnut oxide chloride, micronized polyethylene, mica, ultramarine, eosin dyes, azo dyes, can be mentioned as (micro) pigments. In particular, titanium dioxide or zinc oxide are used in cosmetics as light protection filters and can be applied to the skin particularly smoothly and evenly by means of the emulsions according to the invention. Microspheres or silica gel can be used as carriers for active ingredients, and waxes can be used, for example, as the basis for polishes.

The este polyols according to the invention can also be used as dispersing agents or continuous phase for (micro) pigment dispersions. Systems of this type consisting of este polyols and (micro) pigments according to the invention typically contain 10 to 50% by weight of (micro) pigments, particularly preferably 35 to 45 % By weight of (micro) pigments. The dispersions obtainable from the (micro) pigments and the este polyols can be introduced in water or in oil without the dispersion being adversely affected. It is thus possible, by using the este polyols, to make hydrophilic pigments hydrophobic and to introduce them into an oil phase without the degree of dispersion deteriorating. The invention thus also relates to a dispersion of (micro) pigments and / or insoluble organic compounds in este polyols.

The water phase can also contain glycerol, polyethylene glycol, propylene glycol, ethylene glycol and similar compounds and derivatives thereof.

In a corresponding manner, drugs which are administered orally but which are not stable under the conditions prevailing in the stomach or which are intended to act in other places on the digestive tract can be brought to their place of action with an emulsion according to the invention. This emulsion or dispersion is not broken in the stomach, so that it passes through the stomach unchanged. The active ingredient contained is therefore only subsequently released in the digestive tract by breaking down or dissolving the emulsifier. The choice of emulsifiers can be adjusted to the conditions existing at the sites of action.

The skilled worker is familiar with the use of customary auxiliaries and additives in the emulsions or dispersions.

The EP / O emulsions or dispersions according to the invention can be prepared by known processes, as described, for example, in DE-A-43 41 114 and DE-A-43 41 113. For the preparation, the este polyol / polyol phase and the oil phase, which can each contain emulsifier, are usually heated separately to a temperature in the range from 20 to 90 ° C. and then combined with stirring.

The emulsions or dispersions can be prepared and present as solid or flowable emulsions or dispersions, depending on the composition, the phase volume ratio and the solids content which may be present. These are very stable emulsions or dispersions that have high long-term stability under normal handling conditions. In particular, they meet the usual stability requirements in the temperature range from -5 ° C to + 45 ° C. The droplets or particles present in the emulsion or dispersion are very stable, which is why the emulsions or dispersions are particularly suitable as carriers for many types of active ingredients. The emulsions or dispersions prepared with the aid of the emulsifiers mentioned can be obtained by a simple mixing process with stirring, the stability of the emulsions or dispersions generally being hardly or not influenced by the agitator energy input and the type of stirring tool. Any suitable commercially available stirrer can be used to produce the emulsion or dispersion according to the invention.

The invention also relates to an Esteφθlyol-in-oil dispersion containing Esteφolyolparticles in oil as a dispersant, which are derived from glycerol, ethylene glycol, polyethylene glycol, in which up to 30% of the ethyleneoxy units can be replaced by propyleneoxy units, as a polyol component and aliphatic C ₃ _ ₆ - carboxylic acids, which in addition to a carboxyl group have at least one further functional group selected from hydroxyl and carboxyl groups, are derived as acid components which are solid or glassy at 25 ° C., with an average particle size in the range from 10 to 10,000 nm, at least an emulsifier which forms lamellar structures, the estepolyol particles being able to contain a pharmaceutical, cosmetic, detergent-technological, food-technological and / or agricultural-technological active ingredient dissolved or dispersed in the phase.

This dispersion is in particular an SPN dispersion (solid polyol nanoparticles) analogous to an SLN dispersion (solid lipid nanoparticles), the lipid phase being replaced in whole or in part by the solid este polyols used in accordance with the invention and working in oil instead of water. The structure and production of the SPN dispersion according to the invention is described, for example, in EP-B 0 605 497 and EP-B 0 167 825. The dispersion can be prepared as described there, and the dispersion can contain the pharmaceutically active substances described.

According to one embodiment of the invention, the dispersion is produced by mechanical mixing of the este polyol phase with an oil phase at a temperature above the melting or softening point of the este polyol, the weight ratio of este polyol phase to oil phase being 1: 5 to 5: 1, preferably 2: 1 to Is 1: 2. The mixing is preferably carried out without high-pressure homogenization using stirrers in which the shear effect corresponds to the shear effect of a household stirrer. The mixed phase thus obtained can then be further diluted with oil until a desired degree of dispersion is achieved. Emulsifiers suitable for the preparation of the dispersion are again described in EP-B 0 605 497 or EP-B 0 167 825. The average particle diameter in the solid ester polyol phase is preferably 40 to 1000 nm. The oil phase can contain the additives customary for SPN dispersion, such as gel formers, cross-polymers, cellulose derivatives, xanthan gum, gelatin or pectins. Other ingredients are known to the person skilled in the art.

The emulsions or dispersions according to the invention are preferably used in cosmetic and / or pharmaceutical and / or active ingredient compositions. The invention thus also relates to such cosmetic and / or pharmaceutical and / or agro-active substance compositions which contain at least one of the emulsions mentioned. The cosmetic and / or pharmaceutical compositions can be hand or body lotions, oils, ointments, pastes, gels, lip care products, face care products and similar compositions. The compositions can be used in solid, liquid or aerosol form.

The invention further relates to the use of este polyols as solvents, solubilizers or dispersants for slightly soluble (<10% solubility) or insoluble organic compounds in lipophilic and hydrophilic media. Suitable molecules or groups of molecules are, for example, salicylic acid, sphingosines, ceramides, triteφenic acid such as oleanolic acid, betulinic acid, betulin, ursolic acid, boswellic acid, 18-ß-glycyrrhetic acid, forskolin, sclareolide, andrographolides.

The oils mentioned above can be considered as lipophilic media and aqueous media with a water content of at least 80, preferably at least 90, in particular at least 95% by weight as hydrophilic media. Compounds whose solubility is below 3%, preferably below 1%, in particular below 0.5%, are regarded as insoluble.

The invention also relates to a solution of organic compounds insoluble in lipophilic and hydrophilic media in este polyols, which are structured as defined above.

The invention further relates to the use of este polyols as solubilizers for introducing cosmetic and / or pharmaceutical and / or agroactive ingredients into polyol-in-oil emulsions or polyol-in-oil-in-water emulsions or corresponding dispersions. The emulsions or dispersions according to the invention can have a transport and a depot effect for the active substances contained therein. They can not only act as carriers but also as depots, which allow a delayed release of the active ingredient over a certain period of time.

The emulsions or dispersions according to the invention have the following advantages:

Active substances which are sensitive to oxidation and sensitive to hydrolysis can be encapsulated in a stable manner and in particular in a stable manner over a longer period of time. The emulsions and dispersions according to the invention can reliably prevent moisture attack on the active ingredients.

Active ingredients which are insoluble in hydrophilic and lipophilic media can be administered in the form of an emulsion or dispersion.

The penetration properties of the cosmetic or pharmaceutical compositions can be positively influenced by using the emulsions according to the invention. A depot effect and improved penetration can be achieved in particular in the multiple emulsions described.

The skin permeability barrier is overcome in that by forming liquid-crystalline gel network structures in the multiple emulsions described, an order is established which corresponds to that of the lipid barrier of the skin. In such a carrier system, the penetration properties of the pharmacological and cosmetic active ingredients mentioned are decisively improved. The same applies to the dispersions.

The invention is illustrated by the examples below.

Examples

example 1

Phase A

DGCL Citrate 30.00

GLC lactates 30.00

Ascorbic acid 10.00

Phase B

Dow Coming DC 5225 C Formulation Aid 15.00

Abil EM 97 10.00

Wacker Belsil CM 040 5.00 total 100.00

production:

Heat phases A and B separately to 65 ° C;

Stir phase A until the ascorbic acid is dissolved;

Add phase A slowly to phase B while stirring;

Homogenize until a droplet size below 450 nm is reached;

Cool the batch to room temperature.

Example 2

Phase A

PEG 6000 15.00

Glycerol lactate 40.00

Ascorbic acid 10.00 Phase B

Dow Corning DC 5225 C Formulation Aid 15.00

Abil EM 97 10.00

Wacker Belsil CM 040 10.00 total 100.00

production:

Heat phases A and B separately to 65 ° C;

Stir phase A until the ascorbic acid is dissolved;

Add phase A slowly to phase B while stirring;

Homogenize until a droplet size below 450 nm is reached;

Cool the batch to room temperature.

Example 3

Phase A

PEG 6000 40.00 retinol 5.00 polysorbate 20 5.00

Phase B

Dow Corning DC 5225 C Formulation Aid 25.00

Wacker Belsil CM 040 15.00 total 100.00

production:

Heat phases A and B separately to 65 ° C;

Stir phase A until the retinol is dissolved;

Add phase A slowly to phase B while stirring;

Homogenize until a droplet size below 450 nm is reached;

Cool the batch to room temperature. Example 4

Phase A

DGCL Citrate 25.00

GLC lactates 35.00

Polyphenols 10.00

Phase B

Dow Corning DC 5225 C Formulation Aid 15.00

Abil EM 97 10.00

Wacker Belsil CM 040 * 5.00 total 100.00

production:

Heat phases A and B separately to 65 ° C;

Stir phase A until the polyphenol is dissolved;

Add phase A slowly to phase B while stirring;

Homogenize until a droplet size below 450 nm is reached;

Cool the batch to room temperature.

Claims

claims

1. Use of Esteφolyolen, which differs from

Glycerin, C _2-20 alkylene glycol, poly (C ₂ _ ₂₀ alkylene) glycol, preferably ethylene glycol, polyethylene glycol, in which up to 30% of the ethyleneoxy units can be replaced by propyleneoxy units, polyglycerols, sorbitol, pentaerythritol, as the polyol component and

derive, or mixtures of the este polyols with amino-functional polyols with a melting point of less than 100 ° C. or este polyols of the general formula (I)

(I)

with the meaning

R ¹ C _1-4 alkyl,

R ^{2 is} hydrogen or C _1-4 alkyl, n on average I to 100, m on average 0 to n / 2

as solvents, solubilizers or dispersing agents for organic compounds which are insufficiently soluble or insoluble in lipophilic and hydrophilic media, pharmaceutical, cosmetic, detergent technology, active ingredients in food technology or agricultural technology and as a dispersing aid or continuous phase for (micro) pigment dispersions.

Solution of inadequately soluble or insoluble organic compounds in lipophilic and hydrophilic media in este polyols, which differ from

Glycerin, ethylene glycol, polyethylene glycol, in which up to 30% of the ethyleneoxy units can be replaced by propyleneoxy units, as the polyol component and

aliphatic C _-6- carboxylic acids which, in addition to a carboxyl group, have at least one further functional group selected from hydroxyl and carboxyl groups, as the acid component

(I)

with the meaning

R ¹ C ^ alkyl,

R ^{2 is} hydrogen or C _1- alkyl, n on average I to 100, m on average 0 to n / 2

EO, PO basic building blocks derived from ethylene oxide and propylene oxide, which can be present in any order if both basic building blocks are present.

3. Dispersion of (micro) pigments and / or insoluble organic compounds in este polyols, which differ from Glycerin, ethylene glycol, polyethylene glycol, in which up to 30% of the ethyleneoxy units can be replaced by propyleneoxy units, as the polyol component and

(I)

with the meaning

R ¹ C alkyl,

R ^{2 is} hydrogen or C _1-4 alkyl, n on average 1 to 100, m on average 0 to n / 2

Use of este polyols that differ from

aliphatic C _-6- carboxylic acids which, in addition to a carboxyl group, have at least one further functional group selected from hydroxyl and carboxyl groups, as the acid component derive, or mixtures of the este polyols with amino-functional polyols with a melting point of less than 100 ° C. or este polyols of the general formula (I)

(I)

with the meaning

R ¹ C _1-4 alkyl,

as a solubilizer for the introduction of cosmetic and / or pharmaceutical and / or detergent technology and / or food technology and / or agricultural technology active ingredients in polyol-in-oil emulsions or dispersions or polyol-in-oil-in-water emulsions or dispersions.

5. Esteφolyol / polyol-in-oil emulsion or dispersion containing Esteφolyols, which is different from

aliphatic C _3-6 carboxylic acids which, in addition to a carboxyl group, have at least one further functional group selected from hydroxyl and carboxyl groups, as the acid component derive, or mixtures of the este polyols with amino-functional polyols with a melting point of less than 100 ° C. or este polyols of the general formula (I)

R ^ O-fEO-UPO-j _m R ²

(I)

with the meaning

R ¹ Cι -alkyl,

R ^{2 is} hydrogen or C ₄ alkyl, n on average I to 100, m on average 0 to n / 2

in an esterspolyol / polyol phase immiscible with oil, an oil phase and at least one emulsifier.

6. Emulsion or dispersion according to claim 5, characterized in that lactic acid, maleic acid, tartaric acid or citric acid are used as the acid component in the este polyols.

7. emulsion or dispersion according to claim 6, characterized in that the este polyols are solid or glassy at 25 ° C and may have an average particle size in the range of 10 to 10,000 nm.

8. Emulsion or dispersion according to one of claims 5 to 7, characterized in that there are at least 50% by weight of este polyol in the este polyol / polyol phase.

9. Emulsion or dispersion according to one of claims 5 to 8, characterized in that the Esteφolyol / polyol phase a cosmetic and / or pharmaceutical and / or detergent technology dissolved in the phase and / or contains food technology and / or agricultural technology active ingredient.

10. A process for the preparation of emulsions or dispersions according to any one of claims 5 to 9, characterized in that the Esteφolyol / polyol phase and the oil phase, each of which may contain emulsifier, heated separately to a temperature in the range from 20 to 90 ° C and then can be combined with stirring.

11. Esteφolyol / polyol-in-oil-in-water emulsion or dispersion, containing at least one emulsion or dispersion according to one of claims 5 to 9 and additionally at least one aqueous phase.

12. Use of emulsions or dispersions according to one of claims 5 to 9 or 11 in cosmetic and / or pharmaceutical and / or detergent technology and / or food technology and / or agricultural technology active ingredient compositions.

13. Cosmetic and / or pharmaceutical and / or detergent technology and / or food technology and / or agricultural technology active ingredient composition, comprising at least one emulsion or dispersion according to one of claims 5 to 9 or 11.