EP2485718A1

EP2485718A1 - Use of a compound based on eremophilanolides

Info

Publication number: EP2485718A1
Application number: EP10773870A
Authority: EP
Inventors: Reiner Rittinghausen
Original assignee: Individual
Current assignee: Individual
Priority date: 2009-10-07
Filing date: 2010-10-06
Publication date: 2012-08-15
Also published as: WO2011042469A1

Abstract

The invention relates to a compound based on eremophilanolides, wherein the compound has a plant extract from the furanopetasin variety, said extract being free of pyrrolizidine alkaloids, and/or a plant extract that contains furanoeremophilane compounds from the furanopetasin variety, said compounds being converted into the corresponding eremophilanolides by means of oxidation. The compound is pharmacologically effective and does not exhibit a hepatotoxic potential in contrast to the petasites extract from the petasin variety and furan variety, said extract being free of pyrrolizidine alkaloids.

Description

Reiner Rittinghausen

Aitelstraße 29, 82266 Inning-Bachern

Use of a composition based on eremophilanolides

The present invention relates to a composition based on eremophilanolides and their use, in particular for the production of a dietary supplement or dietetic foodstuff and a pharmaceutically active composition for the treatment of disease states.

Petasites hybridus or the common butterbur is a medicinal plant known since ancient times. Depending on the type of ingredients, a distinction is made according to recent studies, two chemotypes, namely the petasin type and the furanopetasin type. The furanopetasin type, also called furanopetasin variety, contains so-called furanoeremophilans, which are not found in the petasin-type plant.

In the pharmaceutical preparations currently used in the prior art

Petasitic extract and nutritional supplements are, in particular, viscous extracts of the petasin type which have an unpleasant, bitter taste. The furanopetasin type has hitherto not been used for dietary supplements or pharmaceutical preparations as an essential ingredient, since it has hitherto been assumed that only the petasin-type petasins have a pharmacologically active action. Furthermore, it is known from the literature that, in contrast to the petasin type (Petasin chemovariancy), the furanopetasin type (Furano chemovariancyte) has cytotoxic properties.

It also contains petasin extracts of the petasin type and the furanopetasin type

PAs. These pyrrolizidine alkaloids are characterized by considerable hepatic totoxic, carcinogenic and mutagenic, but also cytostatic potentials. The toxicity of the Pyrrolizidinalkaloide is bound, inter alia, to certain structural groups, which have the following structural features:

Double bonds in the 1,2-position of the pyrrolizidine ring;

Esterification of at least the primary hydro-methyl group with a C ₅ or C ₆ -

Carboxylic acid;

Branching of the alkyl side chain with at least one of the nucleic acids.

The highest toxicity and carcinogenicity are probably due to the cyclic diesters. The Pyrrolizidinalkaloide are rapidly absorbed after peroral absorption, their N-oxides only after reduction by the intestinal flora. When metabolised in the liver, the pyrrolizidine alkaloids are converted by mixed-function oxidases into very toxic pyrrole derivatives. These are highly reactive and alkylate under physiological conditions nucleophilic groups of the DNA, such as amino, thiol and hydroxy groups.

Methods for the removal of pyrrolizide maltoids from petasin-type petasites extracts, for example by C0 ₂ extraction, are known.

However, petasin-type petasites have been shown to have cytotoxic and hepatotoxic potential despite complete removal of pyrrolizide maltoids.

The object of the present invention was to provide a composition, the composition comprising a plant extract, obtainable from plant parts of the butterbur, which is free of pyrrolizide maltoids and has no cytotoxic and hepatotoxic potential.

Another object of the present invention was to provide a composition which composition has a pharmacologically active plant extract obtainable from plant parts of butterbur, which is free from pyrrolizide maltoids and has no cytotoxic and hepatotoxic potential. Another object of the present invention was to provide a method for producing a composition, which composition comprises a pharmacologically active plant extract obtainable from plant parts of butterbur, which is free from pyrrolizide maltoids and has no cytotoxic and hepatotoxic potential.

According to the invention, it has been found that a composition comprising eremophilanolides and free of pyrrolizidine alkaloids has no cytotoxic and hepatotoxic potential.

Surprisingly, it has also been found that eremophilanolide extracts, obtainable by oxidation and / or oxidative rearrangement of Furanoeremophilanen, main components of the plant extract of furanopetasin type, has no cytotoxic and hepatotoxic potential.

Furthermore, it has surprisingly been found that the pyrrolizidinalkaloidfreie,

Eremophilanolide-containing composition of the invention obtainable by oxidation and / or oxidative rearrangement of Furanopetasin-type furanoerophilans expressing synthesis of glutathione peroxidase 2 (GPX2) and suppressing an integrin receptor (ECM receptor).

Furthermore, it has surprisingly been found that the pyrrolizidine alkaloid-free,

Eremophilanolide-containing composition of the invention on human hepatocytes does not regulate genes, in particular phase II and phase III metabolism, which can be mechanistically associated with hepatotoxicity.

The furanopetasin type includes for the purposes of this invention all petasinfreien species of butterbur. Further, all the parent plants of the genus Petasites (P.) which also contain furanopetasine-type compounds can be used in the present invention, including P. albus, P. japonicus, P. paradoxus, P. kablikianus and P. spurius. According to the invention, however, the furanopetasin type is preferred.

For the purposes of the present invention pyrrolizidinalkaloidfreier Pfianzenxtrakt means that the content of Pyrrolizidmalkaloiden in the composition, preferably solvent-free Plant extract, <10 ppm, especially <5 ppm, preferably <1 ppm pyrrolizidine alkaloid, and more preferably <0.01 ppm pyrrolizidine alkaloid, and most preferably below the detection limit.

According to the present invention, the content of Pyrrolizidinalkaloiden in the composition, based on 100 mg of solvent-free extract, for example, <1 ug and preferably <0.1 microg.

Unless indicated otherwise, the weights of the composition are based on the total weight of the composition, free from added solvents or extractants.

Free of added solvents or extractants means that a possible residual solvent content in the composition is> 0 wt% to <1 wt%, preferably less than 0.1 wt%, based on the total weight of the composition ,

Solvents may be selected from the group comprising alcohols, such as methanol or ethanol, and / or water.

The furanopetasin-type petasites extracts can be obtained from the plant, plant parts and / or plant cells, with leaves, subterranean plant parts such as rhizomes with foothills and / or roots being preferred. Most preferred is the use of the root. If appropriate, individual substances can also be obtained from a transformed plant, plant parts, and / or plant cells, preferably with

Agrobacterium rhizogenes transformed cultures thereof, in particular transformed Wurzelhaarkulturen be recovered.

The Furanoeremophilane contained in Furanopetasin type can be obtained by oxidation and / or oxidative rearrangement of the Furanoeremophilane in the plant, plant parts and / or plant cells, with leaves, subterranean plant parts, such as rhizomes with foothills and / or roots are preferred converted into Eremophilanolide become. The composition according to the invention may preferably comprise a furanopetasine-type plant extract in which the furano-eremophilanes are converted into eremophilanolides by oxidation and / or oxidative rearrangement.

For the purposes of this invention eremophilanolides are also referred to as Eremophilanlactone.

The Furanoeremophilane contained in Furanopetasin type can be obtained by oxidation and / or oxidative rearrangement of Furanoeremophilane in the plant, plant parts and / or plant cells, with leaves, subterranean plant parts, such as rhizomes with foothills and / or roots are preferred Eremophilanolide be transferred and / or converted by oxidation and / or oxidative rearrangement of Furanoeremophilane in the corresponding extract or corresponding extract fraction / s in Eremophilanolide or Eremophilanlactone.

The Furanopetasmpfianzenextrakt in which the Furanoeremophilane contained are converted by oxidation and / or oxidative rearrangement in Eremophilanolide or Eremophilanlactone, may be a pure plant extract of furanopetasin type and / or a mixture of Furanopetasinpflanzensektktraktion.

A composition in which the furano-eremophilanes are converted to eremophilanolides or eremophilan lactones by oxidation and / or oxidative rearrangement can be obtained from a mixture of furanopetasin plant extract fractions by, for example, combining at least two furanopetasin plant extract fractions which differ from each other, in particular different components the furanoerophilanes contained by oxidation and / or oxidative rearrangement in

Eremophilanolide or Eremophilanlactone are transferred.

The furano-eremophilanes may be partially, preferably substantially and preferably fully converted in the composition into the eremophilanolides or eremophilan lactones.

For the purposes of this invention, "complete" means that the proportion of furano-eremophilanes in the composition is <10 ppm, in particular <5 ppm, preferably <1 ppm and more preferably <0.01 ppm, and most preferably below the detection limit. Preferably, the furano-eremophilanes may be> 50% to <100%, preferably>60%>, more preferably>70%>, more preferably>80%>, even more preferably>90%> and even more> 99 % in the inventive composition in Eremophilanolide or Eremophilanlactone be converted.

According to the invention, the composition can contain furano-eremophilanes with> 0 wt.% To <10 wt.%>, Preferably> 0.0001 wt.% To <8 wt.%>, More preferably> 0.001 wt.%> To <6% by weight, more preferably> 0.01% by weight> to <4% by weight>,%>, more preferably> 0.05% by weight> to <2% by weight> , and furthermore preferably> 0.1% by weight to> 1% by weight, based on the total weight of the composition.

It may be preferred according to the invention that the furano-eremophilanes almost completely and particularly preferably completely in the inventive composition in

Eremophilanolide or Eremophilanlactone are transferred.

The ratio of the proportions by weight of furanoeremophilanes to eremophilanolides in the composition according to the invention may be in the range from 1: 1,000,000 to 1:10 and preferably in the range from 1: 1: 00,000 to 1: 100.

A composition according to the invention which is free of pyrrolizidine alkaloids may contain> 1% by weight to <100% by weight, preferably> 5% by weight to <90% by weight, more preferably> 10% by weight. % to <80% by weight, more preferably> 15% by weight to <70% by weight, furthermore preferably> 20% by weight> to <60% by weight, more preferably> 30% by weight %> to <50% by weight> eremophilanolides, based on the total weight of the composition.

The composition of the invention free of pyrrolizidine alkaloids may have petasins.

The petasins may be selected from the group comprising petasin, neeopetasine and / or isopetasin, iso-S-petasin, neo-S-petasin, S-petasin, 3-deoxy-isopetasol, 3-deoxyneopetasol, isobutyryl-neopetasol, methacryloyl -petasol, methacryloyl-isopetasol, 3-thiomethylacryl neopetasol, 3-thiomethylacrylisopetasol, 3-methylcrotonoyl-neopetasol, 3-methylcrotonoyl-petasol, and / or 3-methylcrotonoyl-isopetasol.

The proportion by weight of petasines, based on the total weight of the composition according to the invention, can be> 0% by weight to <20% by weight, preferably> 1% by weight to <17% by weight, more preferably> 2% by weight. % to <15% by weight, preferably> 5% by weight to <10% by weight, with a petasinfreie composition being most preferred.

According to the invention, the content of petasins in the composition can be in the range from> 0 wt.% To <5 wt.%, In particular <1 wt.%, Based on the total weight of the composition. Most preferably, the composition, especially the furan petasin extract, can be free of petasins, i. the composition contains essentially eremophilanolides and no petasins.

A composition according to the invention which is free of pyrrolizidine alkaloids may have the following components:

> 5% by weight to <100% by weight, preferably> 5% by weight to <95% by weight,

Eremophilanolide; and

> 0% by weight to <40% by weight, preferably> 1% by weight to <5% by weight, petasines;

based on the total weight of the composition, wherein the weight proportions of the components comprising eremophilanolides or eremophilanlactones and petasines are each selected so that together they make up a maximum of 100% by weight of the composition.

The composition of the invention may preferably have the following components:

> 1% by weight to <100% by weight, preferably> 5% by weight to <90% by weight, more preferably> 10% by weight to <80% by weight, more preferably> 15% by weight % to <70% by weight, moreover preferably> 20% by weight to <60% by weight, further preferably> 30% by weight to <50% by weight of eremophilanolides;

> 0% by weight to <40% by weight, preferably> 0.0001% by weight to <30% by weight, more preferably> 0.001% by weight to <20% by weight, more preferably> 0.01% by weight to <10 % By weight,%, moreover preferably> 0.05% by weight to <5% by weight, and furthermore preferably

> 0.1% by weight to <1% by weight of petasins; and

> 0% by weight to <10% by weight, preferably> 0.0001% by weight to <8% by weight, more preferably> 0.001% by weight to <6% by weight, more preferably> 0.01% by weight to <4% by weight,%, moreover preferably> 0.05% by weight to <2% by weight, and furthermore preferably> 0.1% by weight to <1% by weight .-% furanoeremophilanes;

based on the total weight of the composition, wherein the weight proportions of the eremophilanolides, petasines and Furanoeremophilane are each chosen so that together make up a maximum of 100 wt .-% of the composition.

An inventively preferred composition free of pyrrolizidine alkaloids, in addition to the aforementioned components - for example to ad 100 wt .-% - other unspecified sesquiterpene compounds, essential oil, monoterpenes, aliphatic, low molecular oxygenated compounds and hydrocarbons such as nonene have.

The eremophilanolides may be selected from the group comprising 8β-H-eremophilanolide, 8α-H-eremophilanoid, and / or 2-angeloyl-8β-H-eremophilanolide.

The eremophilanolides may be selected from the group comprising 8β-H-eremophilanolide, 8α-H-eremophilanoid, 2-angeloyl-8β-H-eremophilanolide, 2-angeloyl-8α-H-eremophilanolide, 2-senecioyl-8α-H-eremophilanolide , 2-Tigloyl-8a-H-eremophilanolide, 2-tigloyl-8a-H-eremophilanolide, 2-methacroyl-8a-H-eremophilanolide, 2-isobutyryl-8a-H-eremophilanolide, 2-senecioyl-8β-H-eremophilanolide , 2-tigloyl-8β-H-eremophilanolide, 2-methacroyl-8β-H-eremophilanolide, 8β-H-9β-hydroxy-petasitolide-A, 8β-hydroxy-dememanolanolide, 2-methylthioacryloyl-8β-H-eremophilanolide, 9 hydroxy-isobakkenolid,

Petasitolide-A, Petasitolide-B, S-Petasitolide-A, and / or S-Petasitolide-B.

According to the invention, it may be preferred if the composition according to the invention comprises at least one, preferably at least five, more preferably at least ten and more preferably at least 15 eremophilanolides or eremophilanlactones selected from the group comprising 8β-H-eremophilanolide, 8a-H-eremophilanolide, 2-angeloyl 8β-H-eremophilanolide, 2-angeloyl-8a-H-eremophilanolide, 2-senecioyl-8a-H-eremophilanolide, 2-tigloyl-8a-H-eremophilanolide, 2-tigloyl-βH-eremophilanolide, 2-methacroyl-8a -H-eremophilanolide, 2-isobutyryl-8a-H-eremophilanolide, 2-senecioyl-8β-H-eremophilanolide, 2- Methacroyl-8β-H-eremophilanolide, 8β-H-9β-hydroxy-petasitolide-A, 8β-hydroxyeremophilanolide, 2-methylthioacryloyl-8β-H-eremophilanoid, petasitolide-A, petasitolide-B, S-petasitolide-A, and / or S-petasitolide-B, and more preferably, 8β-H-eremophilanolide., 8a-H-eremophilanolide, and / or 2-angeloyl-8β-H-eremophilanolide.

A further composition suitable according to the invention may comprise at least one component, preferably at least five, more preferably at least ten, and most preferably at least 15 selected from the group of 8a-eremophilanolides, 8β-eremophilanolides, 8β-H-eremophilanolide, 8a-H-eremophilanolide, 2 Angoyl-8β-H-eremophilanolide, 2-angeloyl-8a-H-eremophilanolide, 2-senecioyl-8a-H-eremophilanolide, 2-tigloyl-8a-H-eremophilanolide, 2-tigloyl-8β-H-eremophilanolide, 2 -Methacroyl-8a-H-eremophilanolide, 2-isobutyryl-8a-H-eremophilanolide, 2-senecioyl-8β-H-eremophilanolide, 2-methacroyl-8β-H-eremophilanolide, 8β-H-9β-hydroxy-petasitolide-A 8ß-Hydroxyeremo-, and / or 2-methylthioacryloyl-8ß-H-eremophilanoid include.

The composition of the present invention may be a mixture of furanopetasin-type plant extract and petasin-type plant extract. Where compositions free of petasin-type plant extract are most preferred.

The composition of the invention may have a ratio of furanopetasin-type plant extract to petasin-type plant extract of> 100: 1 to 1: <0.1, preferably> 44: 1 to 1: <1 and preferably from 50: 1 to 5: 1, with higher plant extract fractions of the furanopetasine type being preferred in order to avoid the risk of hepatotoxic potential of the composition. For this reason, for example, compositions of the invention which are free of plant extract of the petasin type, in particular free of petasins, are also most preferred.

A preferred composition according to the invention may be the following

Eremophilanolide compounds, based on the total weight of the composition, have:

5% by weight to 40% by weight, preferably 8% by weight to 35% by weight, preferably 15% by weight to 30% by weight of 8β-H-eremophilanolide; 1% by weight to 25% by weight, preferably 3% by weight to 20% by weight, preferably 5% by weight to 15% by weight 8H-eremophilanolide;

0.01% by weight - 10% by weight, preferably 0.1% by weight - 6% by weight, preferably 0.5% by weight - 3% by weight of 8β-hydroxy-eremophilanolide

0.05% by weight to 25% by weight, preferably 0.5% by weight to 20% by weight, preferably 1% by weight to 10% by weight, of 2-angeloyl-8β-H-eremophilanolide ;

0.05% by weight to 20% by weight, preferably 0.5% by weight to 20% by weight, preferably 1% by weight to 10% by weight, of 2-angeloyl-8a-H-eremophilanolide ;

0.01% by weight - 15% by weight, preferably 0.1% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-methylthioacroyl-8β-H -eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-methacroyl-8β-H -Eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-methacroyl-8a-H -Eremophilanolid;

0.01% by weight to 15% by weight, preferably 0.2% by weight to 8% by weight, preferably 0.5% by weight to 5% by weight of 2-senecioyl-8β-H -Eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-senecioyl-8a-H -Eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-tiglioyl-8a-H -Eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-tiglioyl-8β-H -Eremophilanolid;

0.01% w / w - 15% w / w, preferably 0.2% w / w - 10% w / w, preferably 0.5% w / w - 5% w / w 8β-H-9β-hydroxy -Petasitolid-A;

> 0 wt .-% - 8 wt .-%, preferably 0.01 wt .-% - 4 wt .-%, preferably 0.1 wt .-% - 2 wt .-% isobutyryl-8a-H-Eremophilanolid;

> 0 wt .-% - 8 wt .-%, preferably 0.01 wt .-% - 4 wt .-%, preferably 0.1 wt .-% - 2 wt .-% 9-hydroxyiosbakkenolide;

<5% petasin and isopetasine, calculated as isopetasine.

The composition may additionally comprise at least one component, preferably at least two components and more preferably at least three components or else several of the following components:

Antiphlogistic, analgesic, antipyretic; Extracts of Chamomilla recutita, Rhizoma Curcumae longae, Rhizoma Curcumae xanthorrhizae, Curcumae xanthorrhiza, Cortex Salicis, Salicis purpura, Salicis daphenoides and / or Tanacetum parthenium; Rosmarinus officinalis

Trace elements, preferably salts of chromium, iron, iodine, copper, cobalt, magnesium, manganese, selenium and / or zinc;

Secretolytic, secretomotor moiety, preferably extracts of liquorice root, thyme herb and / or peppermint oil;

Bronchospasmolytic, preferably extracts of ivy leaves, calendula and / or viola;

- Vitamin, preferably vitamin A, B, C, D, E and / or K; and / or antioxidant, preferably Q10, lycopene, lutein, zeaxanthin, bioflavonoids, anthocyanidins, grapeseed extract, extracts of various fruits, for example pomegranate, kiwi, cranberry, etc .;

Urinary spasmolytic / antiphlogistic, preferably extracts of pumpkin seeds and sabal fruits;

Antimicrobial plant extract or drug, preferably sabal leaves, essential oils such as eucalyptus oil.

The composition may, but is not preferred, be added to at least one taste-masking substance, the taste-masking substance preferably comprising essential oils, essences, aromatic waters, oily sugar, fruit flavors, aromatic drug extracts, artificial flavorings, sugars, sweetness polyols, neutral-tasting thickening agents, Cyclodextrins and / or mixtures thereof.

Another object of the present invention relates to an agent containing a composition of the invention.

The composition according to the invention can have the composition according to the invention with a weight fraction, based on the total weight of the composition, of> 0% by weight to <100% by weight, in particular> 1% by weight to <95% by weight, preferably > 5% by weight to <90% by weight, more preferably> 10% by weight to <80% by weight, even more preferably> 15% by weight to <70% by weight, more preferably> 20 % By weight to <60% by weight, more preferably> 30% by weight to <50% by weight. However, such agents can also> 0.01 wt .-% to <10 wt .-% of the composition according to the invention, preferably up to 5 wt .-%, in particular up to <1 wt .-% and optionally up to <0.1 wt .-%, based on the total weight of the agent.

Compositions according to the invention may be selected from the group comprising medicaments, foods, food supplements. The agents may be used for medical and / or non-medical purposes, especially dietary and / or nutritional supplementation.

A pharmaceutical composition containing the composition according to the invention may contain the composition with a weight fraction of> 0.01% by weight to <90% by weight, preferably> 0.5% by weight to <80% by weight, more preferably> 1 % By weight to <70% by weight, more preferably> 5% by weight to <60% by weight, further preferably> 10% by weight to <50% by weight, and also preferably> 20% by weight % to <40% by weight, based on the total weight of the drug.

Another object of the present invention relates to a dietary supplement or dietetic food, which has the composition of the invention. The dietary supplement or dietary foodstuff may comprise the composition in a proportion by weight of> 0% by weight to <100% by weight, based on the total weight of the dietary supplement.

According to the invention, the dietary supplement or dietary foodstuff may contain the composition with a weight fraction of> 0.01% by weight to <90% by weight, preferably> 0.5% by weight to <80% by weight, more preferably> 1% by weight to <70% by weight, more preferably> 5% by weight to <60% by weight, further preferably> 10% by weight to <50% by weight, and also preferably> 20 Wt .-% to <40% by weight, based on the total weight of the dietary supplement or dietetic food, have.

The composition according to the invention, the medicament according to the invention and / or the food supplement or dietary food according to the invention can be used for the treatment of disease states and / or for nutritive supplementation. The composition according to the invention, the medicaments according to the invention and / or the food supplement or dietary food according to the invention can be used for the preparation of a pharmaceutically active composition or for nutritive supplementation in the treatment of diseases and / or prophylaxis of diseases comprising joint and bile tissue diseases, arthritis, osteoarthritis , Osteoarthritis, rheumatoid arthritis, chronic polyarthritis, polyps, adenomas, gastrointestinal diseases, gastrointestinal ulcerations, gastroduodenitis, and gastritis, of all kinds, spasms in the gastrointestinal tract, biliary tract dykinesia, colitis, Crohn's disease, thromboembolic disorders, coronary Diseases, cardiovascular diseases, ischemia, peripheral arterial occlusive diseases, inflammatory coronary vessels, myocarditis, myocardial infarction, unstable and stable angina pectoris, transient ischemic attack, apoplexy, reversible ischemic neurological deficit, prolonged ischemic neurological deficit, spinal syndrome, back pain, disc disease, hypertension, headache, migraine, asthma, hay fever, allergic rhinitis, obstructive pulmonary disease, skin diseases, Alzheimer's disease, tuberculosis, eczema, psoriasis, atopic dermatitis, dysmenorrhoea, hypertension, bladder disease, incontinence , painful spasms in the urogenital area, micturition disorders, tumors, tumor pain, neuro-vegetative disorders, restlessness, anxiety, sleep disorders, depression and / or pain.

The use of the composition according to the invention, of the medicament according to the invention and / or of the food supplement or dietetic food according to the invention for nutritive supplementation, treatment of diseases and / or prophylaxis of diseases comprising migraine, asthma, hay fever, allergic rhinitis and / or eczema can be particularly preferred be.

In particular, the pharmaceutically or pharmacologically active composition according to the invention, pharmaceuticals and / or dietary supplements or foods can be foods for use in Alzheimer's, Parkinson's, neurodegenerative diseases, amyotrophic lateral sclerosis, cancer, metastases, chemotherapy, atherosclerosis, diabetes, metabolic syndrome, rheumatoid arthritis, Immunodeficiency, infections, inflammation, cataract prophylaxis and / or thyroid dysfunction may be used. Furthermore, the pharmaceutically or pharmacologically active composition according to the invention, medicaments and / or food supplements or dietary foods may be used for use in atherosclerosis, thrombosis inhibition, cancer, metastases, rheumatoid arthritis and / or Crohn's disease.

Furthermore, the pharmaceutically or pharmacologically active composition according to the invention, medicaments and / or dietary supplements or dietetic foods for use as spasmolytic and / or analgesic, in particular

Spasmoanalgesic, suitable.

In addition, the pharmaceutical composition according to the invention is suitable for the manufacture of a medicament for the long-term treatment or long-term therapy of patients, in particular newborns, infants and small children. But it is also an acute treatment possible, i. no curative use, but immediately at or after the onset of the disease.

A suitable pharmaceutical and / or dietary supplement or foodstuff according to the invention may be formulated such that the administrable daily dose is between 5 mg - 600 mg of the composition of the invention, preferably between 50 mg - 500 mg of the composition, and most preferably 250 mg of the composition.

It is advantageous according to the invention if the respective individual dose of the abovementioned dosage forms is from 5 to 100 mg of the composition according to the invention, preferably from 25 mg to 100 mg of the composition according to the invention.

Particularly preferably, the use of the medicament according to the invention and / or dietary supplement or dietetic food preparation for the preparation of a spasmolytic, analgesic and / or spasmoanalgetic agent may be suitable for the treatment and / or prophylaxis of disease states.

Agents according to the invention, preferably pharmaceuticals and / or dietary supplements or dietetic foods, may be in liquid, gel, solid and / or liposomal form. Compositions according to the invention in liquid form may contain alcohol, such as ethanol, as solvent.

Compositions according to the invention, preferably pharmaceuticals and / or dietary supplements, may be in the form of a spray, an aerosol, a foam, an inhalant, a powder, a tablet, a capsule, a soft gelatin capsule, a chewable tablet, an ointment, a cream Gel, a suppository or as an injection solution.

Compositions according to the invention, preferably pharmaceuticals and / or dietary supplements or dietetic foods, can also be formulated as a tablet, capsule, in particular gel capsule or chewable tablet.

Orally administrable dosage forms may be provided with a gastric juice resistant layer.

Compositions according to the invention can be prepared by a homeopathic process technique.

Another object of the present invention relates to a process for the preparation of the composition according to the invention.

Suitable methods for the C0 ₂ extraction of the drug are described for the petasin type in DE 39 10 831, DE 41 11 141, DE 41 41 749 and WO 00/12107, to which reference is made in its entirety, wherein the Production process according to the invention differs from the processes known in the art in a number of process steps, in particular the oxidation step of the furano-eremophilanes to the eremophilanolides.

In the method according to the invention contained in the furanopetasin drug and / or furanopetasin extract Furanoeremophilane be converted by oxidation and / or oxidative rearrangement in Eremophilanolide or Eremophilanlactone.

The drug may be derived from Petasites hybridus, the furanopetasin-type or a furanopetasin-type and petasin-type mixture, from the plant, parts of plants and / or plant cells, with leaves, subterranean plant parts and / or roots are preferred.

For the oxidation of the furanoerophilanes in eremophilanolides, furanopetasin-type Petasites hybridus or a furanopetasin-type and petasin-type mixture, plant-based, plant-derived and / or plant-cell oxidant, such as oxygen and / or H ₂ O ₂ , preferably H ₂ 0 ₂ in an aqueous phase, are added and optionally subjected to a temperature treatment. Suitable temperatures are in the range of> 30 ° C bar to <80 ° C, preferably> 35 ° C bar to <70 ° C and more preferably from> 40 ° C bar to <60 ° C. The period for the oxidation of the Plant, plant parts and / or plant cells may be 1 hour to 4 weeks, preferably 1 day to 14 days, preferably 3 to 10 days and most preferably 7 days.

According to the invention, it is advantageous to convert the drug into a powder.

According to the present invention, the powdered drug has a particle diameter D ₅₀ of> 1 μιη to <3000 μιη, preferably from> 10 μιη to <2500 μιη, preferably from> 100 μιη to <2000 μιη, more preferably from> 200 μιη to <1600 μιη, from> 300 μιη to <1200 μιη, from> 400 μιη to <1000 μιη and most preferably from> 500 μιη to <800 μιη.

According to the present invention, the powdered drug has a particle diameter D ₇₀ of> 1 μιη to <3000 μιη, preferably from> 10 μιη to <2500 μιη, preferably from> 100 μιη to <2000 μιη, more preferably from> 200 μιη to <1600 μιη, from> 300 microns to <1200 microns, from> 400 microns to <1000 uιη and most preferably from> 500 microns to <800 microns.

According to the present invention, the powdered drug has a particle diameter D90 of> 1 μιη to <3000 .mu.m, preferably from> 10 μιη to <2500 μιη, preferably from> 100 μιη to <2000 microns, more preferably from> 200 μιη to <1600 microns , from> 300 μm to <1200 μm, from> 400 μm to <1000 μm, and most preferably from> 500 μm to <800 μm. The oxidation of the powdered drug with a defined particle size or particle diameter, as indicated above, is advantageous in order to obtain an almost complete oxidation of the furanoerophilanes to eremophilanolides or eremophilan lactones.

If the particle size or diameter varies too much and / or if the drug is used in the form of the plant or plant parts, i. not with a defined particle diameter or particle size, the Furanoeremophilane can not be satisfactorily converted into the corresponding Eremophilanolide or Eremophilanlactone, since the contact with oxygen, which is necessary for the oxidation, does not sufficiently penetrate the drug.

For the purposes of this invention, D ₅₀ means that> 50% by weight of the particles have a defined particle diameter or particle size.

For the purposes of this invention, D ₇₀ means that> 70% by weight of the particles have a defined particle diameter or particle size.

For the purposes of this invention, D ₉₀ means that> 90% by weight of the particles have a defined particle diameter or particle size.

The oxidation can be carried out, for example, by thermal treatment of the drug and / or the extract in the presence of oxygen.

According to the invention, oxygen flow can be supplied to the drug and / or the extract under pressure.

It may be advantageous to pressurize the drug and / or the extract with an oxygen pressure of> 1 bar to <10 bar and expose it to an elevated temperature.

The term "elevated temperature" in the sense of the present invention means a temperature of> 25 ° C. In the method according to the invention, the drug and / or the extract for the oxidation of Furanoeremophilane a temperature of> 30 ° C bar to <80 ° C, preferably> 35 ° C bar to <70 ° C and particularly preferably from> 40 ° C bar exposed to <60 ° C.

The period of oxidation of the drug and / or extract may be 1 hour to 4 weeks, preferably 1 day to 14 days, preferably 3 to 10 days and most preferably 7 days.

In addition, the drug and / or the extract can be oxidized by the addition of chemical oxidants. For example, H ₂ O ₂ can be added to the extract.

In the method according to the invention, the furano-eremophilanes in the drug and / or the extract can be converted, preferably substantially and preferably completely, into the eremophilanolides or eremophilanlactones.

According to the invention, the furano-eremophilanes in the particulate drug can be converted essentially and preferably completely into the eremophilanolides or eremophilanlactones by passing a stream of hot air through them.

Suitable temperatures for the hot air stream may be> 30 ° C bar to <80 ° C, preferably> 35 ° C bar to <70 ° C and more preferably from> 40 ° C bar to <60 ° C.

Good results can be achieved by means of a hot air flow in the range of> 40 ° C bar to <60 ° C, especially 50 ° C ± 2 ° C. Warm air cycles and cold air cycles alternating or differently tempered hot air cycles alternating or as rising and falling heat phase can also be successfully used for the gentle treatment of the drug for the oxidation of Furanoeremophilane in Eremophilanolide or Eremophilanlactone.

The treatment of the particulate drug with a stream of warm air may be 1 hour to 4 weeks, preferably 1 day to 14 days, preferably 3 to 10 days and most preferably 7 days.

The treatment time depends on the amount of drug to be treated. For the purpose of testing whether and with what proportion the furano-eremophilanes have been converted into eremophilanolides or eremophilanlactones, the drug can be analyzed by means of customary analytical methods, such as GC-MS, HPLC-MS, NMR, IR and the like.

For the purposes of this invention, "complete" means that the proportion of furano-eremophilanes in the composition is <10 ppm, in particular <5 ppm, preferably <1 ppm and more preferably <0.01 ppm, and most preferably below the detection limit.

In the method according to the invention, the furano-eremophilanes can be> 50% to <100%), preferably> 60%>, more preferably> 70%>, more preferably> 80%>, even more preferably> 90% and even more be converted to> 99% in the composition according to the invention by means of oxidation in Eremophilanolide or Eremophilanlactone.

In the process according to the invention, the furano-eremophilanes in the drug and / or the extract after the oxidation step may contain> 0% by weight to <10% by weight, preferably> 0.0001% by weight to <8% by weight. >, more preferably> 0.001 wt.%> to <6 wt.%>, more preferably> 0.01 wt.%> to <4 wt.%>,%>, furthermore preferably> 0.05 wt .%> to <2% by weight>, and furthermore preferably> 0.1% by weight> to <1% by weight, based on the total weight of the drug or of the extract.

It is preferred according to the invention if the furanoeremophilanes are completely converted into eremophilanolides or eremophilanlactones already in the drug.

It may be that the C0 ₂ extract of the drug still Furanoeremophilane, which are then converted in the post-treatment steps of the primary extract by oxidation in Eremophilanolide or Eremophilanlactone.

The process according to the invention may comprise the following process steps:

Production of a powder drug from the plant and / or plant parts of Petasites furanopetasin-type hybrid or of a mixture of furanopetasin-type and petasin-type with a defined particle size; Oxidation of Furanoeremophilanen contained in the powder to Eremophilanoliden under elevated temperature, preferably> 30 ° C bar to <80 ° C;

C02 extraction of the drug to give a primary extract after removal of C0 ₂ ;

Wash the primary extract with water to remove

Pyrrolizidinalkaloide (PA), wherein after each washing step, the added water is removed;

Repeated washing of the primary extract in countercurrent with water, optionally with the addition of HCl, wherein after each washing step, the added water is removed, this step can be repeated 1 to 20 times;

Subsequent drying of the primary extract for complete removal of water to obtain the extract according to the invention, preferably by means of thin-film dryer;

Optionally, oxidation of furanoeremophilanes contained in the primary extract and / or in the extract to eremophilanolides at elevated temperature, preferably> 30 ° C bar to <80 ° C.

The use of acids can be used only in very dilute form and / or only in small amounts, since there is a risk that acids attack and decompose the substances contained in the extract, whereby undefined compounds can arise.

For oxidation of the furanoerophilanes contained in the primary extract in eremophilanolides, the aqueous phase and / or the primary extract an oxidizing agent, such as oxygen and / or H ₂ 0 _{2 are} added, the primary extract is subjected to a temperature treatment. Suitable temperatures are in the range of> 30 ° C bar to <80 ° C, preferably> 35 ° C bar to <70 ° C and more preferably from> 40 ° C bar to <60 ° C.

As H ₂ 0 ₂ 3%, 10% and 30% aqueous H ₂ 0 ₂ solutions can be used, with 3% and 10% aqueous H ₂ 0 ₂ solutions are gentler. Most preferably from 3% to aqueous H ₂ 0 ₂ solutions are used. For almost complete or complete oxidation of Furanoeremophilane in Eremophilanolide in the primary extract of this can be added during washing, especially in the wash countercurrent process, additionally with an aqueous H ₂ 0 ₂ solution, wherein the oxidation preferably at a temperature in the range of> 35 ° C until <45 ° C and preferably at 40 ° C ± 2 ⁰ C is performed.

With the aid of a continuous centrifuge, as described in DE 41 41 749 AI, the water content of the primary extract can be lowered to less than 1 wt .-%. It may be advantageous, after at least one washing step, preferably each washing step, to reduce the water content of the primary extract to less than 1% by weight, preferably <0.1% by weight and preferably <0.01% by weight, based on the total weight of the extract, lower.

In the washing of the extract in a countercurrent process preferably> 1 part extract and <0.5 parts of water are used.

The extract according to the invention can be prepared by known separation processes, such as

Chromatography, separated into fractions:

a) about the molecular size,

b) on the polarity by means of adsorption chromatography, such as TLC or HPLC.

Chromatographic separation processes can be distinguished on the basis of the chemical-physical properties of the substances to be separated and the technical implementation of the separation process. Except for the gel filtration, which is based on different transport resistances of the components due to the molecular masses and sizes, chromatographic methods use the adsorption properties of the substance combination of separation mixture, mobile phase and adsorbent for separation. Distribution chromatographic methods are also contemplated. Composition: quality quantity

active substance

Extract of 70% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

* Other lipids in which the extract dissolves include: olive oil, corn oil, soybean oil. Therapeutic plasma concentration 1 to 1000 μg / l.

** Based on the total weight of the extract and a fluctuation of ± 2% by weight>.

Ph. Eur. = European Pharmacopoeia according to the current version for the year 2008 E 172 = iron oxide (dye number for pharmaceuticals)

Example 2

Soft gelatin capsule

Composition: quality quantity

active substance

Extract of 75% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Example 3

Soft gelatin capsule

Composition: quality quantity

active substance

Extract of 80% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70%> Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg * Other lipids in which the extract dissolves include: olive oil, corn oil, soybean oil. Therapeutic plasma concentration 1 to 1000 μg / l.

** Based on the total weight of the extract and a fluctuation of ± 2% by weight.

Example 4

Soft gelatin capsule

Example 5

Soft gelatin capsule Composition: quality quantity

active substance

Extract of 90% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Example 6

Soft gelatin capsule

Composition: quality quantity

active substance

Extract of 95% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Example 7

Soft gelatin capsule

* Other lipids in which the extract dissolves include: olive oil, corn oil, soybean oil. Therapeutic plasma concentration 1 to 1000 μg / l. ** Based on the total weight of the extract and a fluctuation of ± 2% by weight.

, Eur. = European Pharmacopoeia according to the current version for the year 2008 172 = iron oxide (dye number for pharmaceuticals)

Example 8

Soft gelatin capsule

Example 9

Soft gelatin capsule

Composition: quality quantity active substance

Extract of> 99% by weight ** 25.0 mg

Eremophilanoliden

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

** Based on the total weight of the extract.

Example 10

Soft gelatin capsule

Composition: quality quantity

active substance

Extract of 100% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70%> Ph. Eur. 17,12-20,10 mg Non-crystalline Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

** Based on the total weight of the extract.

Example 11

enteric-coated soft gelatin capsule

Example 12

enteric-coated soft gelatin capsule

Example 13

enteric-coated soft gelatin capsule Composition: quality quantity

active substance

Extract of 80% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Coating

Cellulose seacetatphthalate 1.0-15.0 mg

Example 14

enteric-coated soft gelatin capsule

Composition: quality quantity

active substance

85 wt% extract ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Coating

Cellulose seacetatphthalate 1.0-15.0 mg

Example 15

enteric-coated soft gelatin capsule

Composition: quality quantity

active substance

Extract of 90% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70%> Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Coating

Cellulose seacetatphthalate 1.0-15.0 mg

Example 16

enteric-coated soft gelatin capsule

Example 17

enteric-coated soft gelatin capsule

Example 18

enteric-coated soft gelatin capsule Composition: quality quantity

active substance

97% by weight extract ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Coating

Cellulose seacetatphthalate 1.0-15.0 mg

Example 19

enteric-coated soft gelatin capsule

Composition: quality quantity

active substance

Extract of> 99% by weight ** 25.0 mg

Eremophilanoliden

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70% Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg

Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Coating

Cellulose seacetatphthalate 1.0-15.0 mg

** Based on the total weight of the extract.

Example 20

enteric-coated soft gelatin capsule

Composition: quality quantity

active substance

Extract of 100% by weight ** 25.0 mg

Eremophilano lids

excipients

Medium chain triglycerides * Ph. Eur. 245.0 mg

capsule shell

Glycerol 85% Ph. Eur. 23.52-27.60 mg

Dry matter from sorbitol solution 70%> Ph. Eur. 17,12-20,10 mg Non-crystalline

Gelatin Ph. Eur. 80.89-94.96 mg

Iron oxide red E 172 0.47-0.55 mg Glycerol Ph. Eur. 1.60-1.88 mg

Iron oxide black E 172 1.13-1.33 mg

Coating

Cellulose seacetatphthalate 1.0-15.0 mg

** Based on the total weight of the extract.

Example 21

injection

The furanopetasin extract with> 60% by weight **,> 70% by weight **,> 80% by weight **,> 90% by weight ** or> 99% by weight ** Eremophilanolides is mixed 1:10 with highly purified soybean oil with the addition of 0.1-2% by weight of egg lecithin as emulsifier, and the mixture emulsified to 0.5-2.0% by weight in water for injections.

Example 22

Liposomal composition

The liposomes are prepared from glycerophospholipids, cholesterol and stearylamine and at least one lipid derivative, wherein the extract according to the invention with> 60 wt .-% **,> 70 wt .-% **,> 80 wt .-% **,> 90 wt .-% ** or> 99 wt .-% ** Eremophilanoliden in the lipid phase of the liposomes is dissolved.

** Based on the total weight of the extract

Claims

Patent claims

1. Composition, characterized in that the composition

Having eremophilanolides and is pyrrolizidinalkaloidfrei.

2. Composition according to claim 1, wherein the composition is> 1% by weight to <100% by weight, preferably> 5% by weight to <90% by weight, more preferably> 10% by weight to <80 % By weight, more preferably> 15% by weight to <70% by weight, moreover preferred

> 20% by weight to <60% by weight, more preferably> 30% by weight to <50% by weight of eremophilanolides, based on the total weight of the composition.

3. Composition according to claim 1 or 2, wherein the composition contains> 0% by weight to <10% by weight, preferably> 0.0001% by weight to <8% by weight, more preferably> 0.001% by weight. % to <6% by weight, more preferably> 0.01% by weight to <4% by weight,%, more preferably> 0.05% by weight to <2% by weight, and further preferably > 0.1% by weight to <1% by weight of furano-eremophilanes, based on the total weight of the composition.

4. The composition according to any one of claims 1 to 3, wherein the composition comprises the following components:

> 0% by weight to <40% by weight, preferably> 0.0001% by weight to <30% by weight, more preferably> 0.001% by weight to <20% by weight, more preferably> 0.01% by weight to <10% by weight,%, moreover preferably> 0.05% by weight to <5% by weight, and furthermore preferably> 0.1% by weight to <1% by weight .-% Petasins; and

> 0% by weight to <10% by weight, preferably> 0.0001% by weight to <8% by weight, more preferably> 0.001% by weight to <6% by weight, more preferably> 0.01% by weight to <4% by weight,%, moreover preferably> 0.05% by weight to <2% by weight, and furthermore preferably> 0.1% by weight to <1% by weight .-% furanoeremophilanes; based on the total weight of the composition, wherein the weight proportions of the eremophilanolides, petasines and Furanoeremophilane are each chosen so that together make up a maximum of 100 wt .-% of the composition.

Composition according to any one of the preceding claims, wherein the composition comprises at least one, preferably at least five, more preferably at least ten, and most preferably at least 15 eremophilanolide compound (s) selected from the group comprising 8β-H-eremophilanolide, 8a-H-eremophilanolide, 2 Angeloyl 8β-H-eremophilanolide, 2-angeloyl-8a-H-eremophilanolide, 2-senecioyl-8a-H-eremophilanolide, 2-tigloyl-8a-H-eremophilanolide, 2-tigloyl-8β-H-eremophilanolide, 2- Methacroyl-8a-H-eremophilanolide, 2-isobutyryl-8a-H-eremophilanolide, 2-senecioyl-8β-H-eremophilanolide, 2-methacroyl-8β-H-eremophilanolide, 8β-H-9β-hydroxy-petasitolide-A, 8β-hydroxy eremophilanolide, 2-methylthioacryloyl-8β-H-eremophilanoid, petasitolide-A, petasitolide B, S-petasitolide-A, and / or S-petasitolide-B, and more preferably, 8β-H-eremo-philanolide ., 8a-H-eremophilanolide, and / or 2-angeloyl-8ß-H-eremophilanolide.

A composition according to any one of the preceding claims, wherein the ratio of the proportions by weight of furano-eremophilanes to eremophilanolides in the composition is in the range of 1: 1,000,000 to 1:10 and preferably in the range of 1: 1: 1,000 to 1: 100.

A composition according to any one of the preceding claims wherein the composition is a furanopetasine-type plant extract wherein the eremophilan compounds have been converted to eremophilanolides by oxidation and / or oxidative rearrangement.

A composition according to any one of the preceding claims, wherein the composition has a ratio of furanopetasin-type plant extract to petasin-type plant extract of> 100: 1 to 1: <0.1, preferably> 44: 1 to 1: <1 and preferably from 50: 1 to 5: 1

Composition according to any one of the preceding claims, in which the proportion by weight of the following eremophilan compounds, based on the total weight of the composition, comprises: 1% by weight - 40% by weight, preferably 8% by weight - 35% by weight of 8β-H-eremophilanolide; and or

0.1% by weight - 30% by weight, preferably 3% by weight - 20% by weight of 8a-H-eremophilanolide; and or

0.1% by weight to 30% by weight, preferably 4% by weight to 20% by weight, of 2-angeloyl-8β-H-eremophilanolide; and or

0.01% by weight - 20% by weight, preferably 0.2% by weight - 8% by weight of 2-methylthioacroyl-8β-H-eremophilanolide; wherein the proportions by weight of the Eremophilanolide are each selected so that together make up a maximum of 100 wt .-% of the composition.

Composition according to any one of the preceding claims, in which the proportion by weight of the following eremophilan compounds, based on the total weight of the composition, comprises:

5% by weight to 40% by weight, preferably 8% by weight to 35% by weight, preferably 15% by weight to 30% by weight of 8β-H-eremophilanolide;

1% by weight to 25% by weight, preferably 3% by weight to 20% by weight, preferably 5% by weight to 15% by weight 8H-eremophilanolide;

0.05% by weight to 25% by weight, preferably 0.5% by weight to 20% by weight, preferably 1% by weight

10% by weight of 2-angeloyl-8β-H-eremophilanolide;

0.05% by weight - 20% by weight, preferably 0.5% by weight - 20% by weight, preferably 1% by weight

10% by weight of 2-angeloyl-8a-H-eremophilanolide;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-senecioyl-8β-H -Eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-senecioyl-8a-H -Eremophilanolid; 0.01% by weight - 15% by weight, preferably 0.2% by weight - 8% by weight, preferably 0.5% by weight - 5% by weight of 2-tiglioyl-8a-H -Eremophilanolid;

0.01% by weight - 15% by weight, preferably 0.2% by weight - 10% by weight, preferably 0.5% by weight - 5% by weight of 8β-H-9β-hydroxy -Petasitolid-A;

> 0 wt .-% - 8 wt .-%, preferably 0.01 wt .-% - 4 wt .-%, preferably 0.1 wt .-%

2% by weight of isobutyryl-8a-H-eremophilanolide;

> 0 wt .-% - 8 wt .-%, preferably 0.01 wt .-% - 4 wt .-%, preferably 0.1 wt .-%

2% by weight of 9-hydroxyiosbakkenolide;

<5% petasin and isopetasine, calculated as isopetasine; wherein the proportions by weight of Eremophilano lide are each selected so that together make up a maximum of 100 wt .-% of the composition.

11. A composition containing> 0% by weight to <100% by weight, based on the medicament, of a composition according to any one of claims 1 to 10.

12. A composition according to claim 11, wherein the agent is a drug, food or dietetic food.

13. A composition according to claim 11 or 12, wherein the agent between 5 mg to 600 mg, preferably from between 50 mg to 500 mg, and most preferably 100 to 250 mg of the composition according to any one of claims 1 to 8.

14. Use of the agent according to any one of claims 11 to 13 as a medicament for the treatment of disease states.

15. A process for the preparation of the composition according to any one of the preceding claims, wherein in the drug and / or containing in the plant extract of Furanopetasin- chemovarität furanoeremophilans are converted by oxidation and / or oxidative rearrangement in Eremophilanolide.