DE19544905A1 - Preparation of plant extracts - Google Patents

Abstract

Preparation (A) of plant extracts comprises: (a) carrying out a lipophilic extraction of a plant raw material, to give a first extract; (b) fermenting the extraction residue from step (a); (c) subjecting the fermentation broth from step (b) to a hydrophilic extraction, to give a second extract, and (d) combining the first and second extracts. Also claimed is the preparation (B) of plant extracts, comprising: (a) treating plant raw material with an aqueous medium, and fermenting the resulting mixture, and (b) subjecting the resulting fermentation broth to an alcoholic extraction, to give a total extract which contains lipophilic and hydrophilic components.

Description

The invention relates to a method for producing Plant extracts, especially concentrates, which both with lipophilic as well as hydrophilic ingredients of the plant are enriched. Furthermore, the invention relates to the with the help extracts and their use in pharmaceuticals and food products.

The production of plant extracts with gentle loading owns conditions in the field of pharmaceuticals and life Medium manufacturing is of great importance. Various physical chemical techniques are already in use. This is the example of the production of chamomile flower extract briefly explained.

The steam distilla is the most common today tion in the von Günther (The Essential Oils, Vol. 5, 438, van Nostrand publ., Princeton, New Jersey (1952)) Form application. This is the fresh and dried plant zen material usually crushed, in a still filled and the lipophilic, essential oil by introducing Steam is expelled from the drug material used.

Another method involves extraction using a Alcohol-water mixture, which is usually 20-50% (v / v) Contains alcohol, such as ethanol or isopropanol. This me too method is described in detail in the literature (Hänsel, R., Keller, K., Rimpler, H., Schneider, G., (ed.): Hager's hand book of pharmaceutical practice; Springer Verlag, Heidelberg- Berlin, Volume V (1992).

In recent years, higher levels have been achieved high-pressure ex traction with supercritical gases applied. In particular the extraction of lipophilic ingredients with supercritical CO₂ applied to coffee, hops and aromatic plants. The Extrak tion with supercritical CO₂ z. B. in DE-PS 21 27 618 for hops, in DE-PS 21 27 611 for spices, in DE-PS 20 05 293 for coffee and in DE-PS 27 09 033 for chamomile  wrote. In the case of chamomile flowers, however, are only the lipophilic components, in particular matricin, bisabolol, Extract chamazulen and spiroethers in yields of about 60% bar. With this method, enrichment factors of up to 50: 1 can be achieved.

Hydrophilic herbal ingredients won in the Ver past is increasingly of medical importance. About with For example, in the 1980s, the effectiveness became hydro phillic ingredients of the official chamomile recognized. The hy drophilic flavonoid apigenin 7-glucoside and its aglycone Api gen in proved to be very effective in the anti-inflammatory Therapy (Della Loggia, R .: Dtsch. Apoth. Ztg. 125, Suppl. 27.3 (1992)).

Pekic, B. and Zekovic, Z. describe in Biotechnology Let ters (1994), 16, 1323-1328, the auto-fermentation of camomiles tongue blossoms by incubation in sodium acetate puf for 72 hours fer, pH 5.5, at 37 ° C. After the batch has dried (4 days, room temperature), the aglycone formed is ultrasonically extracted a 70% ethanol solution. The authors beat that Use of chamomile auto-fermentation for manufacturing pharmaceutical preparations with a higher apigenin content and there with improved spasmolytic activity. The car films tion of other plant materials is, however, not preferred beat. In particular, there is none in this publication Note, instead of fresh plant material a lipophi Plant pellet obtained by extraction to a fermentation undergo. This document also deals with not with the problem of producing plant extracts, those regarding hydrophilic and lipophilic ingredients are enriched and an ingredient pattern similar to that of the nati ven plant. In addition, according to this document only chamomile tongue flowers for extract production use. However, chamomile tongue flower extracts are in German country is not monographed as a medicinal product.

However, flavonoids are due to their water solubility not to be won by CO₂ extraction. Because of this, are according to the prior art either only essentially flavonoid free chamomile oils with a high content of essential oils (Fa.  Haarmann and Reimer, Holzminden, 1993), or only dry extract with over 1% apigenin 7-glucoside and 0.1% free apigenin (Indena, Como, Italy; Radaelli, C., Formentini, L., San taniello, E .: Apigenin 7-glucoside and its 2 ′ ′ - and 6 ′ ′ acetate from ligulate flowers of matricaria chamomilla; Phytochemistry 19 (1980) 985-986).

DE-PS 27 09 033 mentions a stu in general form extraction of the chamomile drug by the first step supercritical gases and then with a polar Extractant to add other active ingredients as well as flavonoids win. However, there is no information like the Yield of hydrophilic ingredients, such as B. Apigenin, further can be improved.

Chamomile extracts that are both lipophilic and hydrophilic Contain ingredients in enriched form and one of the na tive plant have comparable ingredient patterns, ste not yet available, especially since no suitable manufacturer process exists.

Similar problems exist in the manufacture of plants Zen extracts from other medicinal and aromatic plants, in which both lipophilic and hydrophilic ingredients from Inter are eating. This is especially true for those plants that so probably valuable essential oils as well as other valuable Drug ingredients, such as B. flavonoids or their aglyka, contain.

Other problems in plant extract production arise are derived from the natural fluctuations in flavor and drugs content of the plant material, which is characterized by different Conditions of harvest, drying and storage, the respective Growth climate, the seed used, and other factors caused. It is therefore particularly difficult to medicinal and To produce spice plant extracts of constant quality.

There is thus a first object of the present invention therein, a process for the production of concentrated plants to provide zen extracts, both with regard to lipo phile as well as in terms of hydrophilic ingredients chert and in their ingredient pattern of the native plant essentially correspond.  

In particular, there is the task of producing a method To provide a total chamomile extract, so probably the lipophilic, spasmolytically active components, such as Bisabolol, as well as the hydrophilic, anti-inflammatory Contains ingredients such as apigenin.

Another task is to provide Arz Nei- and spice plant concentrates, with the help of the Mög there is fluctuation in quality due to a standard equalized dosage.

Figure description:

Fig. 1 illustrates the hydrolysis of apigenin-7-glucosid to apigenin and the extraction of these substances from chamomile flowers after having been previously extracted with supercritical carbon dioxide. The content of apigenin 7-glucoside and apigeninin (in mg / 100 ml extract) is shown for different samples:

Sample 1, commercial medicinal extract from chamomile tube flowers with 48% (v / v) isopropanol, without CO₂ extraction, ratio dro ge: extract = 1: 2.5; Sample 2, hydrolysis of the same lot Chamomile flowers at 40 ° C, 2 days and 2.5 more added Parts isopropanol 48% (v / v); Samples 3 and 4, CO₂-extracted Chamomile tube flowers as pellets without hydrolysis; Samples 5 to 17, CO₂-extracted chamomile tube flowers after subsequent two to three days hydrolysis at 40 ° C and concentration below Vacuum. Samples 5 and 6 were additionally vacuum two evaporated several times.

The tasks according to the invention are provided solved a process for the production of plant extracts, which is characterized in that one

• a) vegetable raw material of a lipophilic extraction, before preferably with a supercritical gas, undergoes you get a first extract;
• b) fermenting the extraction residue from step a);
• c) the fermentation broth from step b) a hydrophilic Undergoes extraction, taking a second extract holds, which may be further restricted; and  
• d) the first and the second extract are combined, where you get a total extract.

The first process step, lipophilic extraction, is preferably in a manner known per se with an overcritical medium performed. The technical basis for Ex traction processes with supercritical media are state of the art generally known in the art. The lipophilic extraction step the method according to the invention can for example in Anleh to the in DE-PS 21 27 611, DE-PS 21 27 618, DE-PS 27 09 033 or in Isaac, O., The Marigold, Scientific Verlagsgesellschaft mbH, Stuttgart (1992) described procedure be carried out. At the revelation of this pressure Fonts are hereby fully referenced.

The use of a is also from the prior art Series of supercritical media, such as B. of supercritical Ethylene, pentane, N₂O, or CO₂, known for plant extraction, which are basically used in the context of the invention can. However, the extraction is preferably lipophilic Components in the context of the inventive method Extraction with supercritical carbon dioxide.

Before carrying out the CO₂ extraction, the plants can parts such as B. flowers, in a suitable manner, such as. B. with help a pellet mill, to about a third to about a five of their volume are compressed. This makes active ingredient Enrichments by a factor of about 50: 1 in the lipophilic Phase achievable.

Tresterane remaining after lipophilic extraction in a second process step, a fermentati ven subjected to deglucosidation. To do this, the backlog is out the lipophilic extraction, preferably an aqueous medium Water added. The mostly dry pellets, e.g. B. from CO₂- Extraction material, with warm water in the weight ver Ratio of about 1: 1 to about 1: 3 mixed. The mixing is preferably done by a kneader or gravity mixer over a period of 1 minute to about 4 hours. That on the mixture obtained in this way then becomes a fermentative one Implementation subjected. There is an auto-fermentative De glucosidation of flavonoids. Can instead of water  also suitable additives which favor the fermentation, such as Buffers, for example phosphate or acetate buffers, are used will.

The fermentation is preferably carried out with heating, such as e.g. B. in a heating cabinet. A mixture of the fermenta approach should be carried out at least once a day will. Stir evenly throughout the fermenta duration is also possible. It should also be secured represents that during the incubation in the reaction vessel no Overpressure occurs. The fermentation temperature is around 30 ° C to 50 ° C, preferably at about 37 ° C to 45 ° C, and the Incubation time is about 1 to 7 days, preferably about 3 Days, depending on the selected temperature and type of starting material as.

The course of the reaction can be repeated, for example Sampling and chromatographic analysis of the reaction pro products are monitored.

The fermentation is stopped as soon as desired te (n) reaction product (s) in the desired concentration in Medium is available, or as soon as the implementation has ended. To the Stopping are common methods, such as. B. the increase or lowering the pH of the fermentation broth by Add an, preferably inorganic, acid or base. Before however, the addition of a lower alcohol is given if necessary in a mixture with an aqueous medium, such as. B. water or buffer solution. Preferred examples of suitable low alcohols include ethanol and isopropanol; most before However, isopropanol is added, optionally in a mixture with what ser.

In a third stage of the process the fermentation is carried out undergo another extraction to get the interest hydrophilic ingredients, especially glucosides and to separate the aglyka formed from it during fermentation nen. This can be done in a conventional manner. Is preferred however, extraction with the help of stopping the fermenta tion reaction alcohol used. This should end in one concentration in the range of about 10 to about 60% (w / w) preferably about 25 to 55% (w / w), in particular about 40 to 50%  (w / w). After the extraction, the Alko the content of the extract, if necessary, to a desired value, such as B. by evaporation under vacuum.

According to a special embodiment, the two are made th, hydrophilic extract by

• a) about a part by weight or volume of fermentation broth with about one to three parts by weight or volume of one Water / alcohol mixture, preferably a water / isopro panol mixture, with an alcohol content of at least 30% (w / w) mixed so that the alcohol in a final conc tration of about 20 to 50% (w / w),
• b) the mash obtained in this way, if necessary after a brief period Incubation e.g. B. with stirring at room temperature and the fluid phase in a ratio of about 5: 1 to about 30: 1, preferably about 20: 1, such as B. by part wise or complete evaporation of the liquid portion, and if necessary
• c) the spissum phase thus obtained is further separated, e.g. B. by filtration, sedimentation or centrifugation. This is particularly advantageous if a larger proportion of the enriched flavonoids due to aggregate formation flocculates. By centrifugation or sedimentation of the fe Most spissum phase can by a factor of up to 10: 1 white be enriched.

According to a preferred embodiment, this can be invented procedures according to the invention are carried out as follows:

_* Level a: plant material, such as B. dried camomile tubular flowers, is cut, sieved and ground; then mechanically compressed using a pelleting press (up to a factor of 5: 1, ie 5 volumes of raw material, 1 volume of material to be pressed). Then a CO₂ high pressure extraction (400 bar) according to DE-PS 27 09 033. A spissum concentrate is obtained which contains the essential oils in an enriched form. For example, chamomile flowers have a 60% yield of lipophilic active ingredients. The solvent-free lipophilic extract contains up to 4% bisabolol.

_* Step b: Water with a temperature is added to the solid extraction residue, which is depleted in lipophilic components and has a high proportion of flavonoids (e.g. in chamomile, a ratio of apigenin 7-glucoside to apigenin of about 20: 1) of about + 40 ° C. The weight ratio of plant material to water is about 1: 1 to 1: 3. After intensive mixing for about 1 to 4 hours, fermentation takes place at + 40 ° C for about 2 to 3 days in the open air. The batch is mixed daily for about 1 minute.

_* Stage c: The fermentation process is carried out by adding a water / alcohol mixture with an alcohol content of about 30% to 70% (w / w), such as. B. about 65% (w / w), in a weight ratio of about 1: 1 to 1: 3, such as. B. about 1: 3, (fermentation broth to aqueous alcohol), and intensive mixing for 1 to 4 hours. After mechanical pressing, an increased aglycon content is found in the extract. The fluid phase is then evaporated. For example, the concentration can be carried out using a conventional evaporator process (Sattler, K .: Thermal separation process; Verlag Chemie, Weinheim (1988)). A vacuum of less than 50 mbar and a temperature of 40 ° C. to 80 ° C., preferably 60 ° C., can be set here, since the flavonoids, such as apigenin, are sufficiently thermostable in contrast to the labile essential oils.

_* Level d: This hydrophilic concentrate is combined with the lipophilic extract from the lipophilic extraction to form a concentrated total extract.

With chamomile, for example, in the hydrophilic concentrate a ratio of apigenin 7-glucoside: apigenin from 1:10 to 1:20 can be achieved. The concentrate is a factor of 15: 1 to Concentrated 30: 1 compared to the feed used. This Concentrate can contain about 100 mg / 100ml apigenin 7-glu contain kosid and about 2000 mg / 100ml apigenin.

A total chamomile extract with over 1000 mg / 100ml bisabolol and at the same time over 500 mg / 100 ml apigenin can go to the first Available times using the described method be made.

If necessary, the Ge produced according to the invention velvet extract stabilizing and content-normalizing substances be added, such as. B. propylene glycol.

According to a particularly preferred embodiment, the  Completion of the fermentation of chamomile flowers, which leads to De Glucosidation of Apigenin 7-glucosid leads to Apigenin, which Fermentation batch in a ratio of 1: 3 with an isopropanol Water-solvent mixture (about 30% (w / w) to about 70% (w / w)) mixed and an intense maceration or percolation un thrown. Then the fluid phase is se by pressing parried and reused.

The method according to the invention takes place in particular Use in the production of a highly concentrated camomile len total extract. But it is also applicable to the Extracting from other flavonoid drugs, such as e.g. B. Achillea millefolium (yarrow), aesculus (horse chestnut), Angelica (Angelika), Anthemis nobilis syn. Chamaemelum (Römi chamomile), arnica (arnica), aurantium (orange), betula (Birch), calendula (marigold), Capsicum annuum (papri ka), Cardamonus (cardamons), Carthamus (safflower), Carum carvi (Caraway), cereus, cimicifuga (black cohosh), citronella (Lemon), citrus (lemon), coffea (coffee), coriandrum (co riander), Echinacea (coneflower), Eleuterococcus, Eriodictyon, Filipendula (meadowsweet herb), foeniculum (fennel), gingko biloba (Gingko), Hamamelis virginiana (Indian witch hazel), Helich rysum, Humulus lupulus (hops), Hypericum (St. John's wort), Juglans, Limona (Limone), Majorana (Majoranum), Matricaria cha momilla recutita (chamomile), melilota (stone clover), melissae (me lisse), Myristica fragans (nutmeg), Ononis (Hauhechel), Pas siflora (passion flower), piper (pepper), plantago (Spitzwege rich), polygonum, primula, prunus (peach), robinia (Robinia), rosemary (rosemary), salvia (sage), sambucus (Elder), sarothamnus (broom), Serenoa (Sabal), Sophora (Sophora), Sylibum marianum (Milk Thistle), Tabacum (Tobacco), Theobroma Cacao (Cocoa), Thymus (Thyme), Tilia (Lin de), Tussilago (coltsfoot), Urtica (nettle), Valeriana (Valerian), verbascum (mullein), veronica (angelica); like this such as the production of spice extracts, especially from fen chel, hops, coffee, cardamom, coriander, caraway, marjoram, Bell pepper, tobacco and thyme.

The present invention is based in particular on the surprising finding that the extraction residue  (Pomace) the lipophilic extraction in an advantageous manner further process mentally and then further valuable In Extract substances from it, being particularly advantageous Adhesive enrichment factors of about 8: 1 to about 20: 1 achieved are cash.

Surprisingly, using the Invention according to the process, concentrates are produced which are stable for a longer period of time. In addition, are total tex tracts can be produced that match the Dro gene plant essentially correspond.

The method according to the invention also offers the advantage that by separating the extraction process into a pure lipophilic extraction, a biotechnological intermediate treatment, and another, hydrophilic post-extraction, one up to now the prior art extraction with a Lö mixed solvent of hydrophilic and lipophilic solvents which always led to strong loss of active ingredient, well more can be omitted.

In the case of tobacco and cocoa in particular, the invention can Extraction process due to the selective and aromatic preservation the post-extraction of the hydrophilic flavors a ver improved genuine overall quality of the extract, since the Overall yield of flavorings is increased.

The invention also relates to plant extract Kon concentrates with a particularly high active ingredient or aroma content, wel che obtained using the method according to the invention will. The invention particularly relates to the following Plant extracts that he according to the inventive method are available:

• - Extract from Matricaria chamomilla recutita (chamomile), ge characterized by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) an α-bisabolol content of approximately 0.01 to 5% (w / v),
• c) and an apigenin aglyca content of about 0.1 to 3% (w / v).
• - Extract from calendula (marigold), characterized by
• a) an alcohol content of about 0.5 to 60 (v / v);  
• b) a faradiol content (after esterification) of about 5 to 20% (w / w), and
• c) a flavon content of about 0.01% to 1.0% (w / v), calculated on the basis of isorhamnetin and quercetin.
• - Roman chamomile extract (Anthemis chamaemelum nobi lis), characterized by
• a) an alcohol content of about 0.5 to 60% (v / v); and
• b) a flavon content of about 0.2 to 3% (w / v).
• - Extract from tilia (linden flowers), characterized by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils from about 0.01% to 0.02% (w / v); and
• c) a flavon content of about 0.5 to 10% (w / v), calculated on the basis of quercetin, Kämpfol and Ti liroside.
• - Passiflora extract (passion flower), characterized by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils from about 0.01% to 0.02%, based on coumarin, and
• c) a flavon content of about 0.4 to 4% (w / v), calc net based on Vitexin and C-Apigenin.
• - Carum carvi (caraway) extract, characterized by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils of 3-7% (w / w) with egg carvone content of about 40% to 80% (w / w);
• c) a flavon content of 0.01 to 2% (w / w)
• - Verbascum extract (mullein), characterized by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils from about 0.01% to 0.02% (w / v),
• c) a flavon content of about 0.5 to 5% (w / w), calc net based on apigenin, luteolin, fighter oil and Quercetin.  
• - Sarothamnus (broom herb) extract, labeled by
• a) an alcohol content of about 0.5 to 60 (v / v);
• b) an alkaloid content of about 0.1% to 4% (w / w), calculated as - (-) spartein,
• c) a flavon content of about 0.2 to 4% (w / v).
• - Extract from Hippophae rhamnoides (sea buckthorn) marked by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils of about 0.01 to 0.02% (w / v);
• c) a flavone content as glycosides of about 0.03 mg% to 20 mg%, based on the glycosides Kämpfol, Isorhamne tin and quercetin and their aglyka;
• d) an ascorbic acid content of 0.2 to 1% (w / w).
• - Nicotiana Tabacum extract (tobacco) marked by
• a) an alcohol content of about 0.5 to 60% (v / v);
• b) an essential oil content of 0.01 to 0.02% (w / w);
• - Theobroma cocoa extract (cocoa) marked by
• a) an alcohol content of about 0.05 to 60% (v / v);
• b) a fat content of <about 60% (w / w).
• c) a caffeine content of about 0.3 to 6% (w (w).
• - Coffea arabicum extract (coffee) marked by
• a) an alcohol content of about 0.05 to 60% (v / v);
• b) a caffeine content of about 1 to 6% (w / w) and one Theobromine content of about 0.01 to 2% (w / w).
• - Cola (Kola) extract marked by
• a) an alcohol content of about 0.5 to 60% (v / v);  
• b) a content of essential oils of about 0.01 to 0.02% (f / w) and
• c) a caffeine content of about 1 to 2.5% (w / w).

The invention also relates to a method for Production of plant extracts, whereby one

• a) vegetable raw material, an aqueous medium, preferably Water, and the mixture thus obtained is fermented, in particular a fermentative deglucosidation of the Ingredients, and
• b) the fermentation broth is extracted with alcohol, whereby a total extract of lipophilic and hydrophilic ingredient fe receives.

Fermentation and extraction can be carried out under the Be conditions. The above plant materials can NEN processed, such as chamomile tube flowers in particular.

According to a further preferred embodiment of the invention an extraction process is provided wherein dried, crushed chamomile tube flowers in water dium suspended and up to 3 days at a temperature of fermented about 40 ° C, the fermentation by adding about 15-60% (w / w) alcohol, such as B. ethanol or isopropanol, stops, the lipophilic and hydrophilic ingredients extra and if necessary the extract is concentrated.

Subject of the invention are also means such. B. phar pharmaceutical agents or food additives which he comprise plant extracts obtainable according to the invention.

The abbreviation used in this text (v / v) be records volume% information, (w / v) denotes weight% anga ben, each based on the total volume, and (w / w) designation net weight percentages, based on the total weight.

The present invention will now be apparent from the following Examples explained in more detail.

Experimental part example 1 Extraction of chamomile tube flowers

• a) Lipophilic extraction of the essential oils:
  Drug material (12 kg) from dried chamomile tube flowers (cut, sieved and ground) was mechanically compressed using a pelleting press (factor 5: 1). Subsequently, a CO₂ high pressure extraction (<400 bar) was carried out according to the method of Stahl and Schütz, 1978 (DE-PS 27 09 033). A solvent-free lipophilic extract (I) was obtained (yield 60% of all lipophilic active ingredients) with a bisa bolol content of 3.6%. (Bisabolol is the leading substance for the essential oils).
• b) Hydrophilic extraction of the flavonoids:
  To the solid residue (10 kg) of the lipophilic extraction from stage a) (with a genuine ratio of apigenin-7-glucoside: apigenin = 10: 1; 1.2 mg / ml apigenin-7-glucoside; 0.12 mg / ml Apigenin) was added to water heated to + 40 ° C (1 part solid; 1.5 parts H₂O). The mixture was then mixed intensively with a kneader for 20 minutes. The fermentation was carried out by incubation in a warming cabinet at + 40 ° C for 3 days. The batch was mixed daily with a free air supply for 1 minute.
  The fermentation process was stopped by adding 5 kg of water and 10 kg of isopropanol (66% (w / w) alcohol) and intensive mixing over a period of 4 hours. After mechanical pressing, an extract (12.2 kg) was obtained, which was concentrated in a vacuum evaporator (60 ° C., <50 mbar, 5 h) to give a concentrated hydrophilic extract (II) (300 g).
• c) Extract (I) and extract (II) became a lipophilic hy combined drophile extract.
• d) Test result:
  A genomic ratio of apigenin 7-glucoside to apigenin of 20 to 10: 1 is usually found in a chamomile flower extract (Bauer, R., Wagner, H .: External influences on the flavonoid content of chamomile preparations; Sci. Pharm. 59 (1991) 3-4). In the present example, 14.9 mg / 100 ml of apigenin 7-glucoside and 72.2 mg / 100 ml of apigenin were obtained from a raw extract with 120 mg / 100 ml of apigenin 7-glucoside and 20 mg / 100 ml of apigenin after fermentation. After concentration in a vacuum evaporator, 93 mg / 100 ml apigenin 7-glucoside and 966.5 mg / 100 ml apigenin were reached.

The results are summarized in Table 1.  

Table 1

Chamomile flower extract

Results of similar experiments with other chamomile flower batches are summarized in the accompanying Fig. 1.

Example 2 Marigold extraction

• a) Lipophilic extraction of the essential oils:
  Drug material (12 kg) from dried marigold flowers (cut, sieved and ground) was mechanically compressed using a pelletizing press. Subsequently, a CO₂ high-pressure extraction (up to <400 bar, at 50 ° C) was carried out according to the method described by Quirin et al. A lipophilic extract was obtained in a yield of 6% by weight with an active ingredient content of 9.5% faradiols after saponification of the esters, corresponding to 70% of the lipophilic phase extractable with hexane (see: Quirin, KW; Gerard, D. ; Grau, H .; Grau, G .: (1987), Soap-Oil-Fat-Waxes 113: 539-544).
• b) Hydrophilic extraction of the flavonoids:
  The solid residue (10 kg) from the lipophilic extraction from stage a) (with a genuine quercetin content of 0.3 mg / 100 ml and an isorhamnetin content of 2.0 mg / 100 ml) was added to + 40 ° C heated water (1 part solid: 2 parts H₂O). The mixture was then mixed intensively with a kneader for 20 minutes. The fermentation was carried out by incubation in a warming cabinet at + 40 ° C for 2 days. The mixture was mixed again for 1 minute with free air supply. The fermentation process was stopped by adding 10 kg of isopropanol and intensive mixing over a period of 4 hours. After mechanical pressing, an extract was obtained which was reevaporated in a vacuum (+ 60 ° C, <50 mbar) to form a concentrated hydrophilic spissum extract (II) in a ratio of over 3: 1 (with quercetin 18.0 mg / 100 ml and isorhamnetin 49.6 mg / 100 ml) was concentrated.
• c) Extract (I) and extract (II) became a lipophilic hy combined drophile extract.

The results are summarized in Table 2.  

Table 2

Marigold extract

Example 3 Extraction of chamomile tube flowers Test execution

• a) Fermentation of the flavonoids:
  To drug material (10 kg) from dried chamomile tube flowers, (cut, sieved and ground; with a good ratio of apigenin-7-glucoside: apigenin of about 10: 1), water (1 part of solid : 1.5 parts H₂O). The mixture was then mixed intensively with a kneader for 20 minutes. The fermentation was carried out by incubation in a warming cabinet at + 40 ° C for 2 days. The mixture was mixed again for 1 minute daily with free air supply.
• b) Total extraction:
  The fermentation process was stopped by adding 6.8 kg of water and 14.2 kg of isopropanol in a weight ratio of about 1: 1.5 and intensive mixing over a period of 4 hours. After mechanical pressing, a fluid extract with an isopropanol content of 45.73% (v / v) was obtained.
• c) For comparison purposes, a total extract from the same Chen drug material, but without fermentation perform. A total extract with an iso was obtained propanol content of 48.8%.
• d) Test result:
  The results are summarized in Table 3.

As can be seen from Table 3, fermentation takes place a conversion of apigenin-7-glucoside to apigenin. Overra Unfortunately, the lipophi have changed during the fermentation len shares not changed. Oxidative processes under change The essential oil components could not be determined put.  

Table 3

Concentration of ingredients from chamomile tube flowers

Claims (29)

1. A process for the production of plant extracts, characterized in that

• a) subjecting the raw vegetable material to a lipophilic extraction, whereby a first extract is obtained;
• b) fermenting the extraction residue from step a);
• c) subjecting the fermentation broth from step b) to a hydrophilic extraction, giving a second extract; and
• d) the first and the second extract combined.

2. The method according to claim 1, characterized in that one lipophilic extraction with a supercritical gas, preferably carbon dioxide. 3. The method according to claim 1 or 2, characterized in that the residue from step a) an aqueous medium adds and the mixture obtained in this way undergoes fermentative deglucosidation. 4. The method according to any one of the preceding claims, characterized characterized in that the fermentation temperature is about 30 ° C to 50 ° C, preferably about 37 ° C to 45 ° C, and the Fermentation time about 1 to 7 days, preferably about 3 Days. 5. The method according to any one of the preceding claims, characterized characterized in that the fermentation by addition an alcohol selected from ethanol and isopropanol, optionally in a mixture with an aqueous medium completed. 6. The method according to any one of the preceding claims, characterized in that the second extract is prepared by

• a) sets an alcohol content of about 20 to 60% (w / w) in the fermentation broth,
• b) the mash obtained in this way is mixed, pressed and the fluid phase is concentrated in a ratio of about 5: 1 to about 30: 1, and if appropriate
• c) the phase thus obtained is further separated.

7. The method according to any one of the preceding claims, characterized in that the vegetable raw material is selected from drugs containing lipophilic Ingredients such as essential oils and / or terpenes, and hydrophilic ingredients such as flavonoids. 8. The method according to claim 7, characterized in that the vegetable raw material is selected under Achillea Millefolium (yarrow), aesculus (horse chestnut), angelica (Angelika), Anthemis nobilis syn. chamaemelum (Roman Chamomile), arnica (arnica), aurantium (orange), betula (Birch), cocoa (cocoa), calendula (marigold), cardamon (Cardamom), carthamus (safflower), carum carvi (caraway), Cereus, Cimicifuga (black cohosh), Citronella (Lemon), citrus (lemon), coffea (coffee), coriandrum (Coriander), echinacea (coneflower), eluterococcus, Eriodictyon, Filipendula, Foeniculum (Fennel), Gingko biloba (Gingko), Hamamelis virginiana (Indian Witch hazel), Helichrysum, Humulus lupulus (hops), Hypericum (St. John's wort), Juglans, Limona (Limone), Majorana (Majoranum), Matricaria chamomilla recutita (Chamomile), melilota (stone clover), melissae (melissa), Myristica fragans (nutmeg), ononis, paprica (paprika), Passiflora (passion flower), piper (pepper), plantago (Ribwort plantain), Polygonum, Primula (Primel), Prunus, Marigold (calendula), robinia (robinia), rosemary (Rosemary), salvia (sage), sambucus (elder), Sarothamnus (broom), Serenoa (Sabal fruits), Sophora, Sylibum marianum (milk thistle), Tabacum (tobacco), Thymus, Tilia (Linden), Tussilago (Coltsfoot), Urtica (nettle), Valeriana (valerian), Verbascum (Mullein), Veronica (Angelica).   9. The method according to any one of the preceding claims, characterized in that

• a) dried, crushed chamomile tube flowers compressed and extracted with supercritical carbon dioxide;
• b) the extraction residue from step a) is suspended in an aqueous medium and fermented for about three days at a temperature of about 40 ° C .;
• c) the fermentation is stopped by adding about 20-60% (w / w) alcohol and the hydrophilic constituents are extracted; and
• d) the extracts from stages a) and c), if appropriate after further concentration, combined.

10. Plant extract, obtainable according to one of claims 1 to 9 from Matricaria chamomilla recutita (chamomile), in particular chamomile tube flowers, characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• b) an α-bisabolol content of approximately 0.01 to 5% (w / v),
• c) and an apigenin aglyca content of about 0.1 to 3% (w / v).

11. Plant extract, obtainable according to one of claims 1 to 8 from calendula (marigold), characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a faradiol content of about 5 to 20% (w / w) after esterification, and
• c) a flavon content of about 0.01% to 1.0% (w / v), calculated on the basis of isorhamnetin and quercetin.

12. Plant extract, obtainable according to one of claims 1 to 8 from Roman chamomile (Anthemis chamaemelum nobilis), characterized by

• a) an alcohol content of about 0.5 to 60% (v / v); and
• b) a flavon content of about 0.2 to 3% (w / v).

13. Plant extract, obtainable according to one of claims 1 to 8 from Tilia (linden flowers), characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• b) an essential oil content of about 0.01% to 0.02% (w / v),
• c) and a flavon content of about 0.5 to 10% (w / v), calculated on the basis of quercetin, kaempferol and tiliroside.

14. Plant extract, obtainable according to one of claims 1 to 8 from Passiflora (passion flower), characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils of about 0.01% to 0.02% (w / v), based on coumarin,
• c) a flavon content of about 0.4 to 4% (w / v), calculated on the basis of vitexin and C-apigenin.

15. Plant extract, obtainable according to one of claims 1 to 8 from Carum carvi (caraway), characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• b) an essential oil content of about 3-7% (w / w);
• c) a flavon content of about 0.01 to 2% (w / w).

16. Plant extract, obtainable according to one of claims 1 to 8 from verbascum (mullein), characterized by

• a) an alcohol content of about 5 to 60% (v / v);
• b) an essential oil content of about 0.01% to 0.02% (w / v),
• c) a flavon content of about 0.5 to 5% (w / w), calculated on the basis of apigenin, luteolin, kaempferol and quercetin.

17. Plant extract, obtainable according to one of claims 1 to 8 from sarothamnus (broom), characterized by

• a) an alcohol content of about 5 to 60% (v / v);
• b) an alkaloid content of approximately 0.1% to 4% (w / w), calculated as - (-) sparteine,
• c) a flavon content of about 0.2 to 4% (w / v).

18. Plant extract, obtainable according to one of claims 1 to 8 from Hippophae rhamnoides (sea buckthorn) characterized by

• a) an alcohol content of about 5 to 60% (v / v);
• b) a content of essential oils of 0.01 to 0.02% (w / v),
• c) a flavon content of about 0.03 mg% to 20 mg%, based on the glycosides kämpol, isorhamnetin and quercetin and their aglyka,
• d) an ascorbic acid content of about 0.2 to 1% (w / w).

19. Plant extract, obtainable according to one of claims 1 to 8 from Nicotiana tabacum (tobacco) characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• b) a content of essential oils of about 0.01 to 0.02% (w / w).

20. Plant extract, obtainable according to one of claims 1 to 8 from Theobroma cocoa (cocoa) characterized by

• a) an alcohol content of about 0.05 to 60% (v / v);
• b) a fat content of <about 60% (w / w), and
• c) a caffeine content of about 0.3 to 6% (w / w).

21. Plant extract, obtainable according to one of claims 1 to 8 from Coffea arabicum (coffee) characterized by

• a) an alcohol content of about 0.05 to 60% (v / v);
• b) a caffeine content of about 1 to 6% (w / w) and a theobromine content of about 0.01 to 2% (w / w).

22. Plant extract, obtainable according to one of claims 1 to 8 from cola (Kola), characterized by

• a) an alcohol content of about 0.5 to 60% (v / v);
• (b) an essential oil content of about 0.01 to 0.02% (w / w), and
• c) a caffeine content of about 1 to 2.5% (w / w).

23. Plant extract, obtainable according to one of claims 1 to 8 from sambucus (elderflower) characterized by

• a) an alcohol content of about 5 to 60% (v / v);
• b) a flavonoid content of about 0.5-3% (w / w) based on the glycosides rutin, isoquercitrin, quercitrin, hyperoside and astragalin and their aglyka.

24. Plant extract, obtainable according to one of claims 1 to 8 from Solidago (goldenrod herb) characterized by

• a) an alcohol content of about 5 to 60% (v / v);
• b) a flavonoid content of about 0.5-3% (w / w) based on the glycosides rutin, quercitrin, isoguercitrin, hyperoside, astragalin and kaempferol-3-rutinoside and their aglyka.

25. A composition comprising a plant extract according to one of the Claims 10 to 24. 26. A process for the production of plant extracts characterized in that

• a) vegetable raw material is added to an aqueous medium and the mixture obtained in this way is fermented; and
• b) subjecting the fermentation broth to an alcoholic extraction, whereby a total extract of lipophilic and hydrophilic ingredients is obtained.

27. The method according to claim 26, characterized in that

• a) dried, crushed chamomile tube flowers suspended in an aqueous medium and fermented for up to three days at a temperature of about 40 ° C;
• b) the fermentation is stopped by adding about 15-60% (w / w) alcohol and the lipophilic and hydrophilic constituents are extracted.

28. Plant extract obtainable by a process of Claims 26 or 27. 29. A composition comprising a plant extract according to claim 28.