ES2363448T3 - METHOD FOR THE PRODUCTION OF CONCENTRATED ACTIVE PRINCIPLES. - Google Patents

Abstract

Method for the production of active ingredient concentrates, characterized in that (a) a starting material containing the active substance is contacted with a PIT emulsion, (b) the mixtures are heated to a temperature above the inversion temperature of phases of the PIT emulsion and left there for a sufficient period of time, (c) they are cooled and the mixtures are filtered as well as if necessary (d) they are subjected to ultrafiltration and / or (e) to extraction Additional solvent.

Description

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Field of the Invention

The invention is in the field of plant active ingredients and refers to the use of PIT emulsions as extraction agents.

State of the art

It has long been a tendency to observe the use of active ingredients of non-synthetic but natural origin, both for the production of cosmetic and pharmaceutical preparations as well as for food and food additives. The bases for this are very different: on the one hand the allusion to the consumer about an active principle that has been taken directly from nature and not synthesized in the laboratory, also rewarded with high prices, on the other hand the methods for the extraction of these Active ingredients from predominantly plant sources have been so strongly improved that the active ingredient concentrates thus obtained can also be produced under economically reasonable conditions. Apart from that, many active ingredients are always produced more easily in a cell than in a reactor, even when a synthetic synthesis route is known.

Under the definition "natural raw material" meanwhile, until now, a product, which is obtained by a chemical route, as a rule by extraction, although this method does not undergo any structural change. Normally the production of such extracts occurs by aqueous, alcoholic or aqueous-alcoholic extraction from plants or parts of plants or from leaves or fruits. Fundamentally, all common extraction methods such as maceration, remaceration, digestion, maceration by movement, turbulence extraction, ultrasound extraction, countercurrent extraction, percolation, repercolation, evacolation (extraction under reduced pressure), diacolation or solid extraction are suitable - liquid under continuous reflux, where percolation is the method chosen for technical reactions. As a starting material, fresh plants or parts of plants can be used, although they usually come from dry plants and / or parts of plants, which can be mechanically shredded before extraction. As solvents for carrying out the extractions, organic solvents, water (preferably hot water at a temperature higher than 80 ° C and in particular greater than 95 ° C) or mixtures of organic solvents and water, in particular low-weight alcohols, may be used. Molecular content with more or less high water content, such as methanol, aqueous ethanol, pentane, hexane, heptane, acetone, propylene glycols and polyethylene glycols, as well as ethyl acetate. As a rule, extraction occurs at 20 to 100 ° C, preferably at 30 to 90 ° C, in particular at 60 to 80 ° C.

In the meantime, a disadvantage is that the extraction agent must in each case adjust to the polarity of the desired active principle, which makes it expensive to produce one day that active principle and the next day another active principle in the same installation. Likewise, it is unsatisfactory that also with the help of in each case solvents optimized to the active principle, in short times they can be extracted only from comparatively small quantities

or on the contrary for a high degree of extraction long times are required. The use of oil-in-water emulsions for the extraction of vegetable oils from pressing cakes is known from SU 1763475 A1.

Accordingly, the objective of the present invention was to provide new extraction agents, with which the disadvantages of the prior art could be overcome and with whose help it was possible in particular to achieve high extraction yields in a short time, so broadly independent of the nature of the active ingredient that is going to be extracted, with low technical costs.

Description of the invention

The object of the invention is a method for the production of active ingredient concentrates which is distinguished in that a starting material containing the active principle

(i)

(to)

it is contacted with a PIT emulsion, heated in the mixtures at a temperature above the phase inversion temperature of the PIT emulsion and left there for a sufficient period of time, or

(b)

it is brought into contact with a suitable aqueous mixture of lipids and emulsifiers suitable for the formation of PIT emulsions, the mixture is heated under strong shearing at a

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temperature above the phase inversion temperature under the formation of a PIT emulsion and left there for a sufficient period of time,

(ii) cool and filter the mixtures as well as appropriate

(iii) they are subjected to ultrafiltration and / or

(iv) to another solvent extraction.

Surprisingly, it was found that the extraction of starting materials containing active ingredients, especially plant starting materials, for example roots, leaves, husks, stems, nuggets, seeds, and the like with the help of emulsions above the inversion temperature of phases leads to clearly higher yields in shorter times. In this, the applicability of PIT emulsions is largely independent of the nature and in particular of the polarity of the active substance to be extracted, which facilitates its technical use. Another advantage is that the PIT emulsions can be used immediately as extraction agents or their components - lipids, emulsifiers, water - are added separately to the starting material and then, in the course of extraction, the PIT emulsion is produced in situ .

Active ingredients and their starting materials

Without limiting the present invention, the preferred active ingredients represent active ingredients that are extracted from leaves, flowers, fruits, husks, stems, roots, seeds or nuggets of different vegetables. Typical examples are the extracts of the following vegetables: Ginkgo biloba, Camellia sinensis, Oleacea europensis, Glyzyrrhiza glabra, Vaccinium myrtillus, Trifolium pratense, Litchi sinensis, Vitis vinifera, Brassica oleracea, Punica granatum, Petroselinium astranacyta, incense, Incense, incense. officinalis, Medicago sativa, Valeriana officinalis, Hoodia gordonii, Castanea sativa, Salix alba, Tagetes as well as Hapagophytum procumbens. In the following, the composition and essential active ingredients in the extracts are briefly discussed.

Ginkgo biloba

The active ingredients of the extracts that are obtained from the leaves of the ginkgo tree (Ginkgo biloba) are flavonoidglycosides, which contain among others (iso) quercitinglycoside, kaempferol, kaempferol-3-rhamnoside, isoramnetine, luteolinglycoside, sitosterolglycoside and in particular hexacyclic terpenlactone, the so-called ginkgolides A, B, C, J, M and bilobalides.

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Isoramnetine (R1 = H), kaempferol (R1 = OH), ginkgolida A (R1 = OMe)

Camellia sinensis

Green tea leaves contain a multitude of substances, such as polysaccharides, volatile oils, vitamins, minerals, purines and also alkaloids, such as caffeine, in particular polyphenols, which as a rule are catechins and flavonoids and are also defined like "tea tannins."

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Catechin type Flavonoid type

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Components

R1 R2 R3 R4

(-) - Epicatechin

H H

(-) Epigallocatechin

H OH

(-) Epicatequingalate

Galoil H

(-) Epigallocatequingalate

Galoil OH

Teflavin

H H

Teflavinmonogalate A

Galoil H

Teflavinmonogalate B

H Galoil

Teflavindigalate

Galoil Galoil

Oleacea europensis

The main component of olive tree leaves (Oleacea europensis) is the antioxidant oleuropein, which represents the most important source of hydroxytyrosol.

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Oleuropein Glyzyrrhiza glabra The main component of the extract of the sweet root Glyzyrrhiza glabra is glycyrethrinic acid.

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Glycyretinic acid 10 Vaccinium myrtillus Extracts from common blue berries (Vaccinium myrtillus) contain a mixture of at least 15 different anthocyanosides, such as the following:

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Commonly, the extracts exhibit 20 to 25% by weight of anthocyanosides, 5 to 10% by weight of tannins as well as small amounts of different alkaloids, such as myrtin and epimirtin, phenolic acids as well as quercitrin glycosides, isoquercitrin and hyperoside.

Trifolium pratense

The main components of red clover extract (Trifolium pratense) are isoflavones, such as daidzein, genestein, formononentin and biochanin A as well as their glycosides such as ononin or sisostrine:

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Isoflavonglucoside

R1 R2 R3 R4

Daizidin

H H Glucose H

Genistin

H H Glucose OH

Ononin

H CH3 Glucose H

Sisostrine

H CH3 Glucose OH

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Litchi sinensis

Extracts that are obtained from the rambutan shells (Litchi sinensis) exhibit high content of flavone derivatives, such as 2-phenyl-4H-1-benzopyranos, flavans, flavan-3-oles (catechins, catechin oligomers ), flavan-3,4-diols (leucoanthocyanides), flavones, flavonols and flavonones. However the component

The principal is constituted by condensed tannins, called procyanols (OPC). These substances contain 2 to 8 catechin monomers or a type of catechin, such as procyanidin, proanthocinidine, procyanidels, oligoprocyanidin, leucoanthocyanidin, leucodelfinin, leukocyanine and anthocyanogen. OPC, preferably proanthocyanidin A2 (OPCA2) behaves like vitamin P, especially in view of the inhibition of matrixmetalproteinases.

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Vitis vinifera proanthocyanidine oligomer The main components of the leaves, roots and in particular grape husks (Vitis vinifera) are polyphenols of the

5 OPC type described above. Brassica oleracea The main components of cauliflower extract (Brassica oleracea) are amino acids, in particular methionine and

cysteine as well as glucosinolates, such as glucorafanine. Punica granatum

10 In the extracts of pomegranate (Punica granatum) are found, apart from sugars and citric acid, in particular delfinidin-1,2-glycosides as well as their aglycones. Petroselinium crispum The main component of parsley fatty oil (Petroselinium crispum) is petroselinic acid. Conversely

The extract shows high content of apiol (1-allyl-2,5-dimethoxy-3,4- (methylenedioxy) benzene), as well as apiin, myristin, pinene and selinen.

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Asiatic spark

Main components of the extract of Centella asiatica are highly condensed naphthenic acids, especially Asian acid, madecasic acid as well as their glycosides.

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Asian acid Madecanic acid

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Asiaticoside Madecasicoside Passiflora incarnata Passion fruit extracts (Passiflora incarnata) are rich in flavones of the apigenin and luteolin type as well

as your C-glycoside.

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Apigenin Luteolin In addition they contain 2 "-BD-glycosides, scaphosides and isoscaphosides, isovitexin, isoorientin, vicenin-2, incenin-2, daponanine as well as trace elements, that is, especially calcium, phosphorus and iron. 10 Medicago sativa extracts Alfalfa (Medicago sativa) are rich in isoflavones, such as daidzein, genestein, formononetin, biocanin A and tricine:

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Daidzein Genestein

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Formononetin Biocanina A Tricina

Valeriana officinalis

The main components of the extracts of valeriana officinalis are valerianic acid, valerianone as well as borneolyester.

Castanea sativa

Extracts of horse chestnut (Castanea sativa) contain mainly saponin as well as escina, which represents the mixture of two glycosides, whose aglycone is derived from proteoscigenin, when they are the glucuronic acid sugars or two D-glucose molecules. The two glycosides differ in the nature of the acyl group in the C22 position.

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10 R = tígic acid or angelic acid

While α-escina represents an amorphous powder that melts at 225 to 227 ° C and is easily soluble in water, βescina (which is also defined as flogencil) is present in the form of scales that are practically insoluble in water although easily soluble in water. alcohol.

Hoodia Gordonii

15 Hoodia, especially Hoodia gordonii is a cactus plant, native to South Africa and has been known for a long time as an agent to combat the sensation of hunger. It is reported that in ancient times the Bushmen on their hunting expeditions subsisted for several weeks without food only by chewing on hoodia roots. In past years it was found that the prodigious properties of this plant are related to its high content of especially active steroid glycosides. In 2001/2002 it was had

20 success for the first time in the isolation and characterization of one of these species; since then she is described in the literature as substance P57:

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In the patent literature little has been known so far about Hoodia and Hoodia extracts. However, pharmaceutical preparations are known from the international patent registration WO 98/046243 A1 (CSIR)

25 base of extracts of plants of the genus Trichocaulon or Hoodia, which should have an appetite moderation effect.

Salix alba

The main components of Salix alba extract are phenolglycosides and in particular salicylates such as salicin, salicortin and tremulacin:

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Tagetes

The different species that belong to the genus Tagetes, are rich in carotenoids, particularly in lutein and zeaxanthin Harpagophytum procumbens The main components of the devil's claw extract (Harpagophytum procumbens) are iridoidglycosides,

harpagósids, harpagida and procumbida.

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Iridoidglycoside R = H = Harpagida

R = PhCH = CHCO = Harpagósido

In addition there are stalkose and glycosylated phytosterols (for example β-sitosterol), flavonoids (for example kaempferol, luteolin), phenolic acids and glycosidic esters of phenylpropanoic acid (for example verbacosides, isoacteosides).

Other examples of suitable starting materials, which can be subjected to extraction with PIT emulsions, are citrus peels or roasted and ground coffee beans.

PIT emulsions

An emulsion is understood as a finely distributed mixture of two different liquids (usually not miscible) without visible separation. Hydrophilic liquids mainly form intermolecular forces in the form of hydrogen bonds. The lipophilic liquids, on the contrary, form intermolecular forces of Van-der-Waals. If oil is added in water, the oil floats. Between the water and the oil a boundary surface has been formed as small as possible. The forces mentioned above cannot be minimally formed between the two phases. On the contrary, a boundary surface tension is formed on the boundary surface. This boundary surface tension is the impulse to form a boundary surface as small as possible and thereby prevent the existence of an emulsion. Therefore, special surface-active substances with emulsifying properties are necessary for the formation and stabilization of an emulsion. The boundary surface tension at the oil-water phase boundary surface is clearly reduced by the emulsifier, whereby mixing is now possible. Despite this, emulsions are unstable systems, therefore have limited durability. The so-called "emulsion rupture" occurs, since the size of the boundary surfaces is reduced by the convergence of droplets to larger drops. A PIT emulsion differs from other emulsions in that it forms very stable oil particles in the µm range and can be diluted with water at appropriate temperatures. It is very characteristic that the oil: emulsifier ratio is several times that of normal emulsions, that is, in general, 10 to 20% by weight of emulsifier based on lipid. The production of such systems is sufficiently known from the prior art; as representative of this it refers to the publication of

T. Förster et al. in Cosm. Toil 106, 49-52 (1991) and Int. J. Cosm. Sci. 16, 84-92 (1994).

Lipids

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For the production of PIT emulsions, the following representatives are considered as lipids, for example: Guerbet alcohols based on fatty alcohols with 6 to 18, preferably 8 to 10 carbon atoms, linear C6-C22 fatty acid esters with C6- fatty alcohols Linear or branched C22 or esters of C6-C13 carboxylic acids branched with linear or branched C6-C22 fatty alcohols, such as myristyl myristate, myristyl palmitate, myristyl stearate, myristyl sucrose, myristyl oleate, myristylbehenate, myristyl rucate, cetyl ethylethaterate, cetyl ethyl acetate, cetyl ethyl acetate , cetilbehenato, cetilerucato, estearilmiristato, estearilpalmitato, estearilstearato, estearilisostearato, esteariloleato, estearilbehenato, estearilerucato, isostearilmiristato, isostearilpalmitato, isostearilestearato, isostearilisostearato, isosteariloleato, isostearilbehenato, isosteariloleato, oleilmiristato, oleilpalmitato, oleilestearato, olei Lysostearate, oleyl oleate, oleylbehenate, oleylrucate, behenylmyristate, behenyl palmitate, behenylstearate, behenylyl stearate, behenyl siloleate, behenyl behenate, behenylerucate, erucilmiristato, erucilpalmitate, erucilstearato, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate, erucilylate. Apart from this, linear C6-C22 fatty acid esters with branched alcohols are suitable, in particular 2-ethylhexanol, C18-C38 alkylhydroxycarboxylic acid esters with linear or branched C6-C22 fatty alcohols, in particular dioctyl malate, linear fatty acid esters and / or branched with polyvalent alcohols (such as propylene glycol, dimerdiol or trimertriol) and / or Guerbet alcohols, triglycerides based on C6-C10 fatty acids, liquid mixtures of mono- / di- / triglycerides based on C6- fatty acids C18, esters of C6C22 fatty alcohols and / or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C2-C12 dicarboxylic acids with linear or branched alcohols with 1 to 22 carbon atoms or polyols with 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched C6-C22 fatty alcohol carbonates, com or for example dicaprilyl carbonate (Cetiol® CC), Guerbet carbonates based on fatty alcohols with 6 to 18, preferably 8 to 10 C atoms, benzoic acid esters with linear and / or branched C6-C22 alcohols (for example Finsolv ® TN), linear or branched dialkyl ethers, symmetrical or asymmetric with 6 to 22 carbon atoms per alkyl group, such as dicaprilyl ether (Cetiol® OE), ring opening products of epoxidized fatty acid esters with polyols, oils silicone (cyclomethicone, types of siliciomethicone among others) and / or aliphatic or naphthenic hydrocarbons, such as, for example, scalane, scalene or dialkylcyclohexanes.

Emulsifiers

For the production of PIT emulsions, emulsifiers, for example non-ionogenic surfactants of at least one of the following groups, are considered as emulsifiers:

•

addition products of 2 to 30 mol of ethylene oxide and / or 0 to 5 mol of propylene oxide on fatty alcohols with 8 to 22 C atoms, on fatty acids with 12 to 22 C atoms, on alkylphenols with 8 a 15 C atoms in the alkyl group as well as alkylamines with 8 to 22 carbon atoms of the alkyl radical;

•

alkyl and / or alkenyl oligoglycosides with 8 to 22 carbon atoms in the alkyl (en) yl radical and their ethoxylated analogs;

•

addition products of 1 to 15 mol of ethylene oxide on castor oil and / or hardened castor oil;

•

addition products of 15 to 60 mol of ethylene oxide on castor oil and / or hardened castor oil;

•

partial esters of glycerin and / or sorbitan with unsaturated, linear or saturated fatty acids, branched with 12 to 22 carbon atoms and / or hydroxycarboxylic acids with 3 to 18 carbon atoms as well as their addition products with 1 to 30 moles of oxide of ethylene;

•

partial esters of polyglycerin (average degree of condensation 2 to 8), polyethylene glycol (molecular weight 400 to 5000), trimethylolpropane, pentaerythritol, sugar alcohols (for example sorbitol), alkylglucosides (for example methylglucoside, butylglucoside, laurylglucoside as well as polyglycoside) (for example cellulose) with saturated and / or unsaturated, linear or branched fatty acids with 12 to 22 carbon atoms and / or hydroxycarboxylic acids with 3 to 18 carbon atoms as well as their addition products with 1 to 30 mol of oxide ethylene;

•

mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and / or mixed esters of fatty acids with 6 to 22 carbon atoms, methylglucose and polyols, preferably glycerin or polyglycerin.

•

Mono-, di- and trialkyl phosphates as well as mono-, di- and / or tri-PEG-alkyl phosphate and their salts;

•

wool wax alcohols;

•

polysiloxane-polyakyl-polyether copolymers or their corresponding derivatives;

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block copolymers or polyethylene glycol -30 dipolyhydroxystearate;

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polymeric emulsifiers, such as pemulene type (TR-1, TR-2) from Goodrich or Cosmedia® SP from Cognis;

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polyalkylene glycols as well as

•

glycerin carbonate.

Alkoxylates

The addition products of ethylene oxide and / or propylene oxide on fatty alcohols, fatty acids, alkylphenols or on castor oil represent known products, commercially available. In this, they are homologous mixtures whose average degree of alkoxylation corresponds to the ratio of the amounts of substances of ethylene oxide and / or propylene oxide and substrate, with which the addition reaction is carried out. C12 / 18 fatty acid mono and diesters of ethylene oxide addition products on glycerin are known as re-greasing agents for cosmetic preparations.

Alkyl and / or alkenyl oligoglycosides

The alkyl and / or alkenyl oligoglycosides, their production and their use are known in the state of the art. In particular, its production occurs by reacting glucose or oligosaccharides with primary alcohols with 8 to 18 carbon atoms. With respect to the glycoside radical, both the monoglycoside are suitable, in which a cyclic sugar radical, as well as an oligomeric glycoside with an oligomerization degree of up to about 8, is glycosidically linked to the fatty alcohol. Oligomerization is a statistical average value, which is based on a common homologous distribution for such technical products.

Partial glycerides

Typical examples of suitable partial glycerides are hydroxystearic acid monoglyceride, hydroxystearic acid diglyceride, isostearic acid monoglyceride, isostearic acid diglyceride, oleic acid monoglyceride, oleic acid diglyceride, ricinoleic acid glycerol, ricinoleidic acid linoleic acid, linoleic acid diglyceride, linolenic acid monoglyceride, linolenic acid diglyceride, erucic acid monoglyceride, erucic acid diglyceride, tartaric acid monoglyceride, tartaric acid diglyceride, citric acid monoglyceride, citric acid monoglyceride malic, diglyceride of malic acid as well as its technical mixtures, which may contain even small quantities of triglycerides subordinated to the production process. Also, the addition products of 1 to 30, preferably 5 to 10 mol of ethylene oxide over the mentioned partial glycerides are suitable.

As sorbitan esters are sorbitan monoisostearate, sorbitan sesquiisostearate, sorbitan diisostearate, sorbitan triisostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan dioleate, sorbitan trioleate, sorbitan monoerucate, sorbitan sorbitan, sorbitan sorbitan of sorbitan, sorbitan monoricinoleate, sorbitan sesquiricinoleate, sorbitan diricinoleate, sorbitan triricinoleate, sorbitan monohydroxystearate, sorbitan sesquihydroxystearate, sorbitan dihydroxystearate, sorbitan sorbrate dihydrate, sorbitan sorbrate sorbrate, sorbitan sorbrate , sorbitan monocyrate, sorbitan sesquicitrate, sorbitan dicitrate, sorbitan tricitrate, sorbitan monomaleate, sorbitan sesquimaleate, sorbitan dimaleate, sorbitan trimaleate as well as their technical mixtures. Also suitable are the addition products of 1 to 30, preferably 5 to 10 mol of ethylene oxide on said sorbitan ester.

Polyglycerin esters

Typical examples of suitable polyglycerin esters are polyglyceryl-2-dipolyhydroxystearate (Dehimuls® PGPH), polyglycerin-3-diisostearate (Lameform® TGI), polyglyceryl-4 isostearate (Isolan® GI 34), polyglyceryl-3 oleate, diisostearoyl 3-diisoterateyl polyglyceryl dihydroetheryl (Isolan® PDI), polyglyceryl-3 methylglucose distearate (Tego Care® 450), polyglyceryl-3 beeswax (Cera Bellina @), polyglyceryl-4 caprate (polyglycerol caprate T2010 / 90), polyglyceryl-3 cetyl ether (Chimexane @ NL), polyglyceryl-3 distearate (Cremophor® GS 32) and polyglyceryl polyyricinoleate (Admul® WOL 1403) polyglyceryl dimerate isostearate as well as mixtures thereof. Examples of other suitable polyol esters are

mono-, di- and tri-esters of trimethylolpropane which, if necessary, have reacted with 1 to 30 mol of ethylene oxide or

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of pentaerythritol with lauric acid, coconut fatty acid, tallow fatty acid, palmitic acid, stearic acid, oleic acid, behenic acid and the like.

Anionic emulsifiers

Typical anionic emulsifiers are aliphatic fatty acids with 12 to 22 carbon atoms, such as palmitic acid, stearic acid or behenic acid, as well as dicarboxylic acids with 12 to 22 carbon atoms, such as azelaic acid or sebacic acid.

Amphoteric and cationic emulsifiers

In addition, zwitterionic surfactants can be used as emulsifiers. Zwitterionic surfactants are defined as those superficially active compounds that carry in the molecule at least one quaternary ammonium group and at least one carboxylate group and one sulfonate group. Particularly suitable zwitterionic surfactants are the so-called betaines such as N-alkyl-N, N-dimethylammonioglycinates, for example cocoalkyldimethylammonioglycinate, N-acylaminopropyl-N, N-dimethylammonioglycinate, for example cocoacylaminopropyldimethyl-ammonium glyceryl-3-alkyl-methylinate, and -3-hydroxyethylimidazoline with in each case 8 to 18 C atoms in the alkyl or acyl group, as well as cocoacylaminoethylhydroxyethylcarboxymethylglycinate. Particularly preferred is the fatty amide derivative known under the name CTFA as cocamidopropyl betaine. Likewise, ampholytic surfactants are suitable emulsifiers. Ampholytic surfactants are understood as those superficially active compounds, which apart from a C8 / 18 alkyl or acyl group contain in the molecule at least one free amino group and at least one -COOH-or -SO3H group and which are capable of forming internal salts Examples of suitable ampholytic surfactants are N-alkylglycine, N-alkylpropionic acids, Nalkylaminobutyric acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycine, N-alkyltaurine, Nalkylsarcosine, approximately 2-alkylaminopropyl acids and alkylamino acids 8 to 18 C atoms in the alkyl group. Particularly preferred ampholytic surfactants are Ncocoalkylaminopropionate, cocoacylaminoethylaminopropionate and C12 / 18-acylsarcosine. Finally, cationic surfactants are also considered emulsifiers, where those of the quaternary ester type are preferred, preferably methyl quaternized salts of esters of dihydric fatty acid ethanolamine.

For the production of PIT emulsions, lipids and emulsifiers are used as described above, commonly in amounts by weight in the range of 90:10 to 70:30 and preferably at 80:20 and transformed into the emulsion with the water in quantities 3 to 10 times in a manner known per se, that is, under application of high agitation energy. The emulsions obtainable by this route exhibit an average diameter of droplets in the range of 0.01 to 0.5 µm and preferably 0.03 to 0.3 µm, where preferably at least 50% of all the droplets have a diameter of 0.05 to 0.09 µm and in particular 0.04 to 0.06 µm. Correspondingly to the state of the art, the production of PIT emulsions can occur discontinuously, therefore in batch operation, however it is preferably carried out continuously, since by this means a reduced size distribution of the droplets On the one hand, such products are naturally useful for technical reuse, they are also suitable for example for use in mass discriminations ("screening tests"), which are commonly oriented by aqueous test solutions.

Performing the extraction method

In the first way of operating of the present invention, first of all the PIT emulsion is produced according to one of the methods described above, by using an oil phase and an aqueous phase, where the continuous microreaction production form is preferably used . As a general rule, the starting material containing the active substance is suspended in the PIT emulsion and heated to above the respective phase inversion temperature. If this is not known, then the formation of the emulsion by the conductivity can be followed: with the rising temperature the conductivity decreases with the reduction of the amount of continuous aqueous phase and reaches the zero value above the PIT. The extraction is carried out when reaching or exceeding the PIT for a sufficient period of time, the individual cases can be very different, however as a rule it is at least one hour and rarely is more than four hours. The samples are then cooled again and the insoluble components are filtered off. Concentrates thus obtained from the active ingredient may already represent finished products that can be sold, however in many cases further purification and enrichment is recommended. To them belong in particular a new separation of the PIT emulsion in an aqueous phase and an oil phase which is achieved for example by rupture of the emulsion by ultrafiltration or membrane filtration. Analytically it is verified that - depending on the active principle - a very large part, that is to say more than 80 and in particular more than 90% of the active principles - as a rule lipophilic - are in the organic phase. Likewise, the organic phase can now be used as such as a product for sale for example for the cosmetic industry. However, it is possible to use another solvent extraction and enrich the active ingredients in a polar organic phase, from which it is obtained in solid form by crystallization or spray drying or freezing.

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Alternatively, extraction is also performed by insitu formation of PIT emulsions. For this purpose, instead of the ready PIT emulsions, their individual components are used here and heated with the starting materials containing the active ingredient, above the phase inversion temperature. This preferably occurs by application of stirring energy, to generate droplets as small as possible.

The advantage of this way of operating is that wet material is also used for the extraction, the extraction components are chosen according to operational requirements (for example explosion risk prevention), by selecting the surfactant / oil mixture the control is controlled. selectivity, and the type of process conduction makes it possible to adjust an effectively minimal boundary surface tension.

Commercial applicability

Another objective of this patent registration concerns the use of PIT emulsions as extraction agents for starting materials that contain active ingredients, in particular plant materials, especially their leaves, flowers, fruits, husks, stems, roots, seeds or nuggets. .

Examples

Example 1

Discontinuous production ("batch") of a PIT emulsion

In a 250 ml flask, 3.1 g of glycerin stearate (Cutina® GMS), 6.9 g of Ceteareth-12 (Eumulgin® B1), 22.5 g of dicaprilyl ether (Cetiol® OE) were mixed with intense stirring ), 22.5 g of dioctylcyclohexane (Cetiol® S), 5 g of glycerin and 40 ml of water and heated over a period of 140 min from 25 ° C to 95 ° C. The mixture was then cooled again in a period of 20 min to the starting temperature. To follow the formation of the emulsion, conductivity was monitored as a function of time. Figure 1 shows the course curve.

image 1

Fig. one

Temperature / conductivity diagram

The conductivity drops with the rising temperature and around the PIT temperature reaches the zero value; with falling temperature the conductivity increases again. This is to clarify that below the PIT temperature an oil-in-water emulsion is present, in which the water represents the continuous phase, above the PIT temperature the oil then forms the phase continues, which leads to the loss of conductivity In the course of the curve it also clearly indicates the formation of a PIT emulsion. The mixture thus obtained showed the known properties for PIT emulsions, that is to say high stability, any miscibility with water, very small droplet size as well as a slight bluish hue. In addition, samples were taken and their droplet size was determined with a Coulter LS apparatus for particle size measurement (illustration 2)

image 1

Fig. 2

Particle size distribution in batch production of PIT emulsions

Example 2

Continuous production of a PIT emulsion

For the rapid tempering and subsequent rapid cooling in the continuous production of the PIT emulsion, a micromixer of the Starlaminator 30, IMM type was interconnected with two heat exchangers. Two 15-liter double jacketed glass reactors served as vessels for the water and oil phases; The flow chart is shown in illustration 3.

image 1

10

Fig. 3

Flowchart for continuous production of PIT emulsions

They were placed separately in a supply tank and preheated to T = 60 ° C the oil phase consisting of 1.24 kg of Cutina® GMS, 2.76 kg of Eumulgin® B1, 9.00 kg of Cetiol® OE and 9.00 kg of Cetiol® S 15 as well as the aqueous phase consisting of 2 kg of glycerin dissolved in 16 kg of distilled water. In this, both phases were stirred. The two phases (oil phase: aqueous phase -1.22: 1) were pumped into the micromixer with two different volume streams (6 L / h and 12 L / h) and mixed there. The mixture was heated in a heat exchanger at 85 ° C directly after the StarLam30 mixer, so that the phase inversion temperature (81 ° C) was exceeded. The emulsion was then cooled in a heat exchanger at a temperature of T = 25 ° C and assembled in a storage container. After the micromixer and after the two heat exchangers a sample was taken in each case and its temperature was determined and

conductivity. Before the first heat exchanger, the conductivity was at approximately 55 µS / cm, after the first heat exchanger it dropped to a value of 0.1 µS / cm to rise after cooling the emulsion to approximately 60 µS / cm. This could prove the formation of true PIT emulsions.

Additionally, samples were taken and their droplet size was determined with a Coulter LS particle size measuring device (illustration 4).

image 1

Fig. 4

Particle size distribution in continuous production of PIT emulsions

The average particle sizes are approximately 0.125 µm smaller than the particle sizes 10 that were reached in the batch method (approximately 0.165 µm).

Example 3

Extraction of plant materials with PIT emulsions

Different starting plant materials (olive leaves, orange peels, coffee powder) were shredded and added to an emulsion produced according to examples 1 or 2. Then the seeds were heated

15 preparations under stirring for 4 h at a temperature of approximately 90 ° C, that is near the phase inversion temperature. After cooling, they were filtered first than all mixtures to separate insoluble residues, and then subjected to ultrafiltration to generate an aqueous phase and an oil phase. The content of plant active ingredients in the two phases was determined by extraction with acetonitrile and subsequent HPLC analysis. The results are compiled in table 1:

20 Table 1 In this way it was possible to show that the plant active ingredients are very predominantly enriched, that is, in amounts between 85 and 97%, in the oil phase.

Extraction of aqueous and oily phase

Starting material

Aqueous phase [mg] Oil phase [mg] Total amount [mg] Fraction of the active substance in the oil phase [%]

Olive leaves

60.0 340.0 400.0 85

Orange peel

46.0 114.0 160.0 91

Coffee powder

2.4 91.6 94.0 97

Example 4 PIT emulsions compared to other extraction agents

1 kg of olive leaves were treated with in each case 2 liters of different extraction agents for 4 h at 90 ° C and then the oleuropein content was determined by HPLC; the highest content was equal to 100% and all other results referred to it. Table 2 compiles the results:

Table 2

Oleuropein Extraction

Extraction agent

Oleuropein Content

PIT emulsion according to example 2

100

Ethanol

74.3

Acetonitrile

42.0

Ethyl methyl ketone

40.7

Dicaprilyl ether

0

10 The results clearly show that approximately 25% more active substance is extracted by using PIT emulsions than with the standard ethanol extraction agent.

Example 5

In situ extraction of zeaxanthin and lutein

2 kg of an oil phase according to example 2 were mixed at T1 = 50 ° C with 750 g of flowering taget leaves

15 per t = 30 min. Then 5 liters of distilled water were added and the mixture was heated to T2 = 95 ° C (ΔT = 0.5 ° C / min). After cooling, they were filtered first of all mixtures, to separate insoluble residues and then subjected to ultrafiltration to generate an aqueous phase and an oil phase. The content of zeaxanthin and lutein - referred to the total amount - amounted to 92% in the oil phase and 8% in the aqueous phase.

Claims (8)

1. Method for the production of active ingredient concentrates, characterized in that (a) a starting material containing the active substance is contacted with a PIT emulsion, (b) the mixtures are heated to a temperature above the phase inversion temperature of the PIT emulsion and left there for a sufficient period of time,

(C)

the mixtures are cooled and filtered as well as appropriate

(d)

they are subjected to ultrafiltration and / or

(and)

to additional solvent extraction.

2. Method for the production of concentrated active ingredients characterized in that 10 (a) a starting material containing an active ingredient is contacted with an aqueous mixture of lipids and emulsifiers, suitable for the formation of PIT emulsions, (b) the mixture is heated under strong shear at a temperature above the phase inversion temperature to form a PIT emulsion and is left there for a sufficient period of time, (c) the mixtures are cooled and filtered as well as given case 15 (d) they are subjected to ultrafiltration and / or (e) to another solvent extraction. 3. Method according to claims 1 and / or 2, characterized in that as starting materials containing the active ingredient leaves, flowers, fruits, husks, stems, roots, seeds or vegetable seeds are used, which are chosen from the group formed by Ginkgo biloba, Camellia sinensis, Oleacea europensis, Glyzyrrhiza glabra, 20 Vaccinium myrtillus, Trifolium pratense, Litchi sinensis, Vitis vinifera, Brassica oleracea, Punica granatum, Petroselinium crispum, Centella asiatica, Passiflora incarnata, Melissa officinalis, Medicago sativa, Valeriana officinalis, Hoodia gordont, Castanea albatiates, Castanea albatiates, Castanea albatapates as Castanea albaumiates, Castanea albaivatum, Castanea albaivatum, Castanea albaivatum, Castanea albatapates procumbens 4. Method according to at least one of claims 1 to 3, characterized in that citrus fruits or coffee powder peels are used as starting materials containing active ingredients. Method according to at least one of claims 1 to 4, characterized in that PIT emulsions are used, which contain lipids and emulsifiers in weight ratios 90:10 to 70:30.

6.

Method according to at least one of claims 1 to 5, characterized in that either PIT emulsions are used or produced, which exhibit a droplet size distribution in the range of 0.01 to 0.5 µm.

7.

Method according to at least one of claims 1 to 6, characterized in that they are used or

30 produce PIT emulsions insitu, which exhibit a droplet size distribution in which at least 50% of all the droplets have a diameter in the range of 0.05 to 0.09 µm. 8. Use of PIT emulsions as extraction agents for starting materials that contain active ingredients. 9. Use according to claim 8, characterized in that the starting materials containing active ingredients represent leaves, flowers, fruits, husks, stems, roots, seeds or pepitpepitasas.