DE3446219A1 - Process for the production of a composition with antiinflammatory effect - Google Patents

Abstract

Process for the production of a composition which has an antiinflammatory effect and which contains at least 30 mg% chamazulene, and at least 100 mg% (-)- alpha -bisabolol and less than 50 mg% other bisaboloids from a tetraploid and bisabolol-rich camomile.

Description

Process for the preparation of a new agent with

anti-inflammatory effects drugs and cosmetic products Preparations of the flower heads of the real chamomile (Chamomilla recutita (t.) Rauschert, synonymous with Matricaria chamomilla L.) because of their anti-inflammatory and spasmolytic effect a wide use.

The active ingredients (-) - C <-Bisabolol are of particular importance and Chamazulen too. A remedy made from chamomile should therefore be as good as possible have a high content of these two substances.

There has now been a method of making a new agent using beneficial properties found using tetraploid chamomiles.

The object of the invention is to produce a new agent with anti-inflammatory effect, which is characterized in particular by an increased content in bisabolol and chamazulene, with the chamazulene content at least 30 mg%, bisabolol at least 100 mg% and the content of other bisaboloids less than 50 mg%.

The term "other bisaboloids" means in particular: (-) - α-bisabolol oxide A and B; (-) -α-Bisabolonoxid A.

The invention relates to the subject matter defined by the claims or facts.

The following camomiles are used to produce the agent according to the invention uses: Well-known diploid chamomiles, where (-) - 6 (-Bisabolol is the main component of the essential oil.

These camomiles are tetraploidized (genome mutation), the resulting tetraploid plants selected from and selected from these tetraploid plants In turn, the plants are selected whose flowers, dried at 40 ° C, have a minimum content of chamazulene of 100 mg%; a minimum content of (-) - O <-Bisabolol of 200 mg% and have a content of other bisaboloids of at most 50 mg% (harvest of the Flowers at the point in time when 30-70% of the tubular florets of a flower head have opened are), and optionally further customary selection and propagation steps connected (parent tree breeding for vegetatively reproducible cross-pollinators) The initial diploid chamomiles are obtained from the following chamomiles, for example: German "Kamille (see L.Z. Padula, R.V.D. Rondina and J.D. Coussio, Quantitative Determination of Essential Oil, Total Azulenes and Chamazulene in German Chamomile, Matricaria chamomilla, Cultivated in Argentina; Planta med. 30, pages 273-280, 1976) as well as all camomiles which have clearly measurable concentrations in the essential oil an (-) - O (-Bisabolol (usually more than 5% of the essential oil), for example Such diploid camomiles come into question, which are described in the following literature references are: Schilcher, H. More recent findings in quality assessment of chamomile oil or chamomile flowers ", Planta med.

23: 132-144 (1973); Motl, O., M. FelklovE, V. Lukes & M. Jasicova "For gas chromatographic analysis and chemical types of chamomile oil", Arch. Pharm. 310: 210-215 (1977); Franz, Ch., J. Hölzl & A. Vömel ¢ Preliminary Morphological and Chemical Characterization of some Populations and Varieties of Matricaria chamomilla L. ", Acta Hort. 73, 109-114 (1978).

The diploid chamomile variety DEGUMILL is also used as the starting chamomile (German Patent 24 02 802) in question. In this case, too, one obtains, for example a tetraploid chamomile with a chamazulene content of at least 150 mg% and one Bisabolol content of at least 200 mg% if the chamomile flower heads are harvested this chamomile takes place in the vegetation stage where only 30 - 70% of tubular flowers of a head are open, and drying at an air temperature of at most 500 C is carried out.

By subsequent selection and propagation steps according to this Registration-the specified bisabolol and azulene values can also be found here further increase.

The essential oil of chamomile (blossom) usually consists of the Main components Farnese, Spathulenol, Chamazulen (or Matricin), one the 4 bisaboloids ((-) - «- bisabolol, bisabolol oxide A, bisabolol oxide B or bisabolon oxide, as far as the individual plant is concerned; in the mixed sample of the population several Bisaboloids are contained next to each other) as well as from the spiroethers. The mentioned Together, substances usually make up 70-80% of the essential oil. Particularly suitable are hence diploid starting chamomiles, where (-) - o (-Bisabolol is the predominant component (more than half of the sum of the aforementioned substances). In particular Diploid chamomiles come into question as starting chamomiles, for example the (-) - «- Bisabolol at least 40% of the essential oil or at least 90% of the bisaboloids represents.

In particular, such diploid ramilla populations come into consideration, which in the mixed drug sample usually contain at least 100 mgE chamazulene and 50 - have 100 mg% (-) - d-bisabolol (based on the dry substance of the 400 C dried flowers), that is, such chamomile populations become seeds obtained and this seed tetraploidized (without consideration and / or knowledge the bisabolol content of the parent plants).

The suitable initial diploid chamomiles are determined by examinations of individual plants selected out.

Generally it is required from an initial population for example Examine 1000 - 10000 individuals to find some individuals that have one have a high (-) - «bisabolol content according to the criteria given above and are suitable as starting chamomile. From such selected individuals then becomes seeds obtained in the usual way and tetraploidized. After the completed The tetraploid plants are tetraploidized from the rest of the plants that have remained diploid Plants selected.

Of the tetraploid plants obtained in this way, optionally after the previous one Propagation, all the plants are now selected, those that have dried at 400 ° C Flowers at least 100 mg% chamazulene, at least 200 mg% (-) - OC-bisabolol and less than 50 mg% of the rest Contain bisaboloids. The harvest of this Flowers takes place in the development stage where 30 - 70% of all tubular flowers of the flower head are open. If necessary, further selection and Follow propagation steps that, for example, an improvement with regard to the following characteristics or properties: Simultaneous flowering date, uniform basal branching and narrow flowering zone (that means better suitability for mechanical harvest), large flower heads, better shelf life of the drug, particularly aromatic smell.

It is particularly favorable if, in the selection according to the Chamazulen- and (-) - & -Bisabolol content of such plants (known or manufactured according to the process) are selected from whose chamazulene content at least 200 mg%, preferably 250 mg% and their (-) - d-bisabolol content is at least 300 mg%, preferably 400 mg% (Content of other bisaboloids always below 50 mg%).

The tetraploidization can be carried out in a manner known per se by treatment parts of plants (seeds, roots, shoot tips, germs, axillary buds) or tissue of the original diploid chamomile plants with chemicals, X-rays, gamma rays or UV rays.

It can continue through anther culture or through the application of high or low temperatures on the chamomile plants or plant parts or tissue of the chamomile plants. This is done, for example, on the Book by Werner Gottschalk "The importance of polyploidy for the evolution of the Plants ", Gustav Fischer Verlag, Stuttgart, 1976, in particular pages 13 to 22 referenced.

Tetraploidization by chemicals.

The chemicals used for tetraploidization are, for example, in Question: Colchicine, acenaphthene, alkaloids such as atropine, veratrine, nicotine, sanguinarine, Derivatives of benzene, diphenyl and phenanthrene, naphthalene and naphthalene derivatives, Diphenylamine, tribromaniline, paradichlorobenzene, methylnaphthoquinone, methylnaphthohydroquinone, Salicylic acid and related substances, hexachlorhexane, methamphetamine (hydrochloride), Alkyl alkali carbamates such as isopropyl sodium carbamate, phenyl urethane, salts of the Cacodylic acid (e.g. sodium salt), glycosides of convallaria such as convallarin, Convallatoxin and convallamarin, heteroauxin, germisan (phenylmercuric catechin), organic mercury compounds such as ethyl mercury phosphate, ethyl mercury chloride, Phenyl mercury hydroxide, phenyl mercury dinaphthyl methane disulfonate, chloroform, Laughing gas (N2O) and mixtures of these substances. There are also oil cakes and compost and cow dung into consideration.

The treatment with the substances mentioned here takes place, for example at temperatures between 0 and 350 ° C., preferably between 12 and 300 ° C., in particular 15 and 250 C.

The application takes place, for example, by treating seeds, Shoot tips, roots (especially root tips or roots of seedlings), Ovaries, from cut surfaces on leaves or stems, from cell suspensions from meristem tissue, from callus cultures or by injection into the basal Stem region or in the area of the axillary buds. The chemicals are generally in the form of solutions in water, weakly alcoholic (alcohol content usually less than 5%) or weakly acidic solutions.

The pH of the weakly acidic solutions is, for example, 5.5 - 6.5, the acidification for example by means of lower organic aliphatic Acids like acetic acid takes place. If you use alcoholic solutions, you can this will also be slightly acidic. The concentrations of the chemicals in these Solutions can be, for example, 0.01 to 0.5%, preferably 0.02 to 0.2%, in particular 0.05 to 0.1%. Gaseous substances come as such, possibly under Pressure (for example 1 to 10 bar) are used. The duration of treatment is, for example 1 to 36, preferably 2 to 12, especially 4 to 6 hours.

The most effective concentrations as well as the duration of exposure should suitably be tested in preliminary tests.

Treatment with colchicine, for example, is particularly beneficial Temperatures between 0 and 350 C, preferably 12 to 300 C, in particular 15 to 250 C. This can be done, for example, by having seeds of the diploid Starting chamomile in a 0.01 to 0.2% strength, in particular 0.02 to 0.1% strength, preferably 0.05 show that colchicine solution is caused to swell or that germinated, 5 up to 7 days old well-developed seedlings of the diploid parent chamomile (with the Cotyledons down) into a 0.01 to 0.2%, in particular 0.02 to 0.1%, preferably 0.05% colchicine solution are immersed. In the latter case the surrounding atmosphere should have almost 100% relative humidity. The duration of the colchicine treatment is, for example, 3 to 36 hours, in particular 4 to 10 hours. When using seedlings, there is generally an exposure time sufficient for up to 10 hours. When using seeds, the exposure time can increase extend up to 36 hours if necessary.

After the treatment with the chemicals, the swollen seeds, Seedlings, or other parts of the plant, rinsed several times with water. For example, the soaked seeds are sown. The plants treated with Roots or other parts of plants or the treated seedlings are for example pricked out in plant boxes. From the seeds or seedlings treated in this way the plants are raised (for example in a greenhouse: temperature between 18 to 250 C during the day and 10 to 160 C at night) and the plants selected whose Pollen are about 1 1/2 times larger than the pollen of the starting material respectively have a somatic cell chromosome number of 36.

If you have other parts of the plant (above or below ground) If subjected to the chemical treatment, only those from the treated Share emerged shoots, roots or flowers / seeds for a later examination on tetraploidization that has taken place subjected. For example, if a shoot treatment or an armpit treatment is carried out afterwards only the new shoot arising from this armpit or from this shoot and the flowers or seeds formed on it examined for the number of chromosomes.

The pollen size measurements and the chromosome count can for example carried out as indicated in Example 3.

Tetraploidization by rays.

The action takes place, for example, on seeds or root tips at temperatures between 0 and 350 ° C., preferably 10 and 300 ° C., in particular 15 and 250 C.

Total exposure: 5 to 50 Krad. Preferably gamma or X-rays in question.

UV rays, for example, come with one wavelength from 400 to 30 nm, preferably from 350 nm in question.

The so irradiated plants or plant parts are then treated in the same way as after treatment with chemicals.

Use of high and low temperatures.

Temperatures between, for example, come as high temperatures 33 and 500 ° C., preferably 42 to 450 ° C., are possible. These temperatures are for example exposed: swollen seeds, seedlings, shoot tips and meristematic tissue. Duration of treatment: for example 1 to 48, preferably 12 to 24 hours.

Examples of low temperatures are: orb to 5 ° C, preferably 0.5 to 40 C, in particular 20 C. These temperatures are for example way exposed: swollen seeds, seedlings, shoots and meristematic tissue. duration of treatment: for example 1 to 100, preferably 20 to 40 days.

The plants or parts of plants treated in this way are the same further treated as after treatment with chemicals.

Anther culture (creation of plants with a single set of chromosomes from the anthers with subsequent tetraploidization by chemicals or Rays).

Closed tubular flowers are harvested from flowering plants, whose anthers (anthers) are in the stage before the first pollen mitosis. The anthers are removed from the flower buds using a micromanipulator and transferred into Petri dishes, for example with the nutrient medium according to Nitsch and Nitsch (Table 1) are filled. The Petri dishes are then placed in a culture room stored in the 16-hour day at 280 C day and 200 C night temperature. After approx four weeks the anthers begin to break open and small plants to grow out. These are haploid in the diploid parent and dihaploid in the tetraploid parent; she are potted in garden soil, for example, after the roots have formed and in the greenhouse brought to bloom. These (di) haploid plants are sterile, but can pass through Sprout tip, root or stem treatment with chemicals such as Colchicine can be polyploidized, producing homozygous plants that grow then let it propagate via seeds. For further procedure, see under treatment with chemicals (for example colchicine treatment).

Table 1 Culture medium according to Nitsch and Nitsch (Science, 1969) mg / l KNO3 950 NH4NO3 720 MgSO4 x 7 H2O 185 CaCl2 166 KH2PO4 68 MnSO4 x 4 H2O. 25 H3BO3 10 ZnSO4 x 7 H20 10 Na2MoO4 x 2 H2O 0.25 CuSO4 x 5 H2O 0.025 5 ml of a solution 7.45 g of ethylenediaminetetraacetic acid disodium salt and 5.57 g of FeSO4 x 7 H2O to 1000 ml myo-inositol 100 glycine 2 nicotinic acid 5 pyridoxine HCl 0.5 thiamine HCl 0.5 folic acid 0.5 biotin 0.05 sucrose 20 g ready-to-use culture medium (DIFCO-Bacto-Agar) 8 g indole acetic acid 0.1 pH of the medium adjusted to 5.5 From the by pollen size measurement and / or chromosome counting of selected tetraploid chamomile plants that are after the possibilities described above can be obtained, then the Plants selected that have a minimum content of chamazulene of 100 mg% and one Have a minimum content of bisabolol of 200 mg%, while the content of the rest Bisaboloids (especially bisabolol oxides) below 50 mg% (based on the dried Flowers, see example 1).

The plants selected in this way will already be after they have been removed Open flower heads in the greenhouse at 18 - 24 ° C day and 12 - 140 C night temperature and a day length of at least 14 hours, with about one Period of 4 weeks for all flower heads that have faded or are about to decay are harvested for seed production. After drying at an air temperature between 20 - 350 C, for example, the reproductive material of such a chamomile is obtained.

The the following are used: a) approximately simultaneous flowering, b) uniform, Basal branching and a narrow flowering zone of around 10, especially 5 cm, c) large flower heads with an outer diameter of about 30 mm (20 to 40 mm), in particular 25 - 35 mm, The application of the additional criteria a), b) and / or c) leads, for example, to high flower and drug yields and better suitability for machine harvesting.

To get a chamomile that except a content of at least 100 mg% chamazulene and at least 200 mg% (-) - O (-Bisabolol (based on the dried Flower heads) also has a high flower yield and for the machine If harvesting is more suitable, the following procedure is recommended: The selected Plants (as described above) are propagated vegetatively by cuttings and over 3 to 5 generations read out, the selection always being according to the above Criterion and, if applicable, the additional criteria a) - c). According to Plants selected according to these criteria are cloned from the cloned plants If seeds are obtained, the plants obtained therefrom in turn according to the above Minimum content of chamazulene and bisabolol and, if applicable, the additional Criteria a) - c) selected from and seeds obtained again from the latter.

The sequence of sowing - selection according to the minimum content given above of chamazulene of 100 mg% and (-) - oL-bisabolol of at least 200 mg% (other bisaboloids below 50 mg%) and, if applicable, the additional criteria a) - c) - seed production can be repeated 3 - 5 times.

This is followed by another sowing sequence - as indicated above Selection (possibly cloning) - seed production on.

The seed obtained last is then the propagation material of the invention Chamomile.

The propagation of cuttings takes place in the following way: For propagation of cuttings the parent plants (clone mother plants) must be free of flower buds under short-day conditions Form short shoots. This is done in the greenhouse without additional lighting in the winter half-year or in climatic chambers with a day length of 6 to 10, preferably 8 hours and Temperatures from 10 to 150 C, preferably 120 C. For cloning respectively Propagation are suitable for leaf, shoot and especially rump shoot (side shoot) cuttings. Their rooting takes place at 12 to 180 C, preferably 150 C and day lengths of 12 to 16, preferably 14 hours in a stressed atmosphere (approx. 100% relative Humidity). For example, a peat-sand mixture can be used as a substrate 1: 1 can be used; however, pure quartz sand, rockwool cuttings cubes are also suitable, Peat cuttings cubes and the like.

For example, the following soils can be used for sowing: Garden soil; humus, medium-heavy clay soils; loamy or humus sandy soils.

It can be sown in the greenhouse or outdoors. the Temperatures for germination and growth of the plants are, for example, between 12 to 240 C, in particular 18 to 200 C. If sown outdoors, this is preferred sown in autumn (September / October) or in spring (March / April). These dates apply to all possible cultivation areas (e.g. northern hemisphere, temperate to subtropical climates).

It is particularly favorable if the following process conditions are used Application come: From the tetraploid chamomile plants that have a minimum content of chamazulene of 100 mg% and of (-) - d-bisabolol of 200 mg%, while the content of other bisaboloids (especially bisabolol oxides) is below 50 mg% (all values related to the dried flower heads), only those are selected, which - bloom approximately at the same time - a uniform basal Branches and a narrow flowering zone of approx. 10 cm as well as - large flower heads have an outside diameter of approx. 30 mm.

The plants selected from are propagated vegetatively using cuttings and read out over 3 - 5 generations, whereby the selection is always based on the above Criteria takes place. The selected plants are propagated vegetatively (cloned), let bloom together, and the seeds are obtained from this. The ones from the Plants obtained from seed are again obtained according to the criteria given above selected and the sequence sowing-selection-seed production-sowing is 3 - 5 times repeated.

The chamomile, which is used for the preparation of the agents according to the invention belongs to the cultivated plant species of real chamomile with the botanical name Matricaria Chamomilla IJ. (synonym Chamomilla recutita (L.), Rauschert). That at a temperature of not more than 700 C dried material from the flowers of these Chamomile, which is harvested at the vegetation stage where 30-100% of tubular flowers of a flower head are open, contains at least 30 mg% chamazulene, at least 100 mg% d-bisabolol and less than 50 mg% of other bisaboloids.

If the chamomile flowers are harvested at a time in where the flower development stage is more advanced, that is, where for example 100% or up to 100% of all tube flowers of a flower head are open (at Example stage of the whole leaves) and / or if the harvested flowers are dried takes place at a temperature higher than 40 ° C, the content of the active ingredients (-) - d-Bisaboo and Chamazulen be lower because of higher drying temperatures and / or at A greater breakdown of the azulene and bisabolol can occur later in the harvest.

For example, contain those dried in a drying cabinet at 400 C. Flowers (harvested as indicated above) of the chamomile according to the method between 100 up to 200 mg% chamazulene, between 200 to 450 mg% (-) - d-bisabolol and only a little, that means between 5 to 50 mg% other bisaboloids based on the dry substance (i.e. based on the absolute dry weight of the flowers).

This absolute dry weight is obtained by drying a separate Sample of chamomile flowers in a drying cabinet at 1050 C until constant weight (72 up to 96 hours). The active ingredient content of, for example, 35 to 500 C dried flowers is then determined at 1050 C to the dry mass of the flowers calculated.

A particularly effective remedy is obtained (with maximum salary on the active ingredients chamazulene and (-) - OC-bisabolol) when the chamomile flower heads are harvested takes place in the vegetation stage where, for example, 30 to 70%, preferably 40 up to 60%, that is to say generally 50% of the tubular flowers of a flower head are open are and drying at an air temperature of at most 500 C, for example 35 to 500 C, in particular 400 C takes place. For example contained in the drying cabinet Flowers dried at 40 ° C (harvested where 40-60% of the tubular flowers of a flower head are open) at least 100 mg%, for example between 100 to 150 mg% chamazulene, at least 200 mg%, for example between 200 and 300 mg% (-) - a-bisabolol and only little, i.e. between 5 to 50 mg% of other bisaboloids based on the dry substance (i.e. based on the absolute dry weight of the flowers). This absolute Dry weight is determined by drying a separate sample of chamomile flowers in the Drying cabinet determined at 1050 C to constant weight (72 to 96 hours).

The active ingredient content of those dried at, for example, 35 to 50 ° C Flowers is then calculated on the basis of the dry mass of the flowers determined at 1050 C.

The drying of the chamomile flowers can either be done by artificial air supply or by drying in the shade, possibly also in the sun, However, care should be taken that the heat supply does not use the to complete drying is required. So it is advantageous that one can convince oneself of the achieved weight constancy by checkweighing. the Drying can take place spontaneously or artificially (for example with artificial warm air). The active ingredient yield is greatest with spontaneous drying with the exclusion of the Sunlight, preferably at 40 - 600 C, especially 40 - 500 C.

The drying process should be carried out as soon as possible or immediately take place after the harvest. Drying should be done in thin layers, for example from 5 to 20 cm, preferably 10 cm thick. The drying is for example also in well-ventilated halls with an air temperature between 20 - 300 C possible. In general, the air temperature should not be used for drying higher than 600. C. For example, an air temperature between 35 is favorable and 500 C.

The active ingredient content of the agents according to the invention, in particular at the main active ingredients chamazulene and (-) - d-bisabolol, depends on the vegetation stage, in which the chamomile flowers are at the time of harvest and from drying of the harvested flowers. The higher the drying temperature, the stronger it is the degradation of the active ingredients, that is, the lower the content of the dried Flowers on the active ingredients.

For the same reason, it has direct sunlight when drying an adverse effect and should be avoided if possible.

The vegetation stage of a flower is characterized by how much % of tubular flowers one Flower head at a specific point in time (here the time of harvest) are open. So flowers can be harvested where, for example, between 30 - 50%, 30 - 70%, 40 - 60%, 60 - 100% or 90 - 100% of the tubular florets of a head are open; The active ingredient content is dependent of the stage in which the flowers are and it is in the chamomile, which is used according to the invention, greatest when 40-60% of all tubular flowers are open and decreases as the percentage of tubular florets opened of a flower head increases. It is therefore a great advantage of this chamomile, that with her the blooming of the individual plants takes place evenly, that is, that from a sowing the majority of the plants each have the same flowering stage have, that is, for example, in the vast majority of plants 40 - 60 % of all tubular flowers of a flower head are open at the same time. This ensures that the flower heads are fully recorded at the optimal point in time possible.

The chamomile, which is used for the preparation of the agents according to the invention is therefore particularly suitable for mechanical harvesting.

The connection between the content of chamazulene and (-) - oL-bisabolol on the one hand with the flowering stage at the time of harvest and on the other hand with the drying temperature the following table shows, for example, how to obtain the agents according to the invention (the content of other bisaboloids is in all cases less than 50%).

Drying stage of vegetation of the flowers at the time of harvest temperature 30 - 70% of all tubular flowers - 70 - 100% of all tubular flowers of a flower flower of a flower temperature) head open head open Active substance content in the active ingredient content in the dried material: dried material: not higher Chamazulene: Chamazulen: as 500 C at least 100 mg% at least 40 mg% (-) - α -Bisabolol: (-) - α-Bisaholol: at least 200 mg% at least 120 mg% active ingredient content in the Active ingredient content in the alcoholic extract: alcoholic extract: not higher Chamazulen: Chamazulen: as 500 C at least 5.0 mg% at least 2.0 mg% (-) - i-Bisabolol: (-) - «-Bisabolol: at least 10.0 mg% at least 6.0 mg% active ingredient content in the active ingredient content in the dried material: dried material: between chamazulene: chamazulene: 50-70 ° C at least 50 mt% at least 30 mg% (-) - α-bisabolol: (-) - α-bisabolol: at least 150 mg% at least 100 mg% active ingredient content in the active ingredient content in the alcoholic Extract: alcoholic extract: between chamazulene: chamazulene: 50-70 ° C at least 2.5 mg% at least 1.5 mg% (-) - α-bisabolol: (-) (-) - «- bisabolol: at least 7.5 mg% at least 10 mg% From this it follows that from chamomile, the is used to produce the agents according to the invention, for example at a harvest that takes place in the vegetation stage, where between 30-100% of tubular flowers the flower heads are open and drying at tuft temperatures up to 70C C, a dry material is obtained, the chamazulene content of which is in in each case at least 30 mg% and its (-) - d-bisabolol content at least 100 mg% while the content of other bisaboloids is always less than 50 mg%.

The alcoholic extracts contain the remaining bisaboloids always lower than 10 mg%.

The essential oil content, which according to the conditions of the the above table is made from a dried material, Chamazulene and bisabolol are always at least 3.5% chamazulene, at least 10 % (-) - «- bisabolol and less than 10% of other bisaboloids.

The chamomile, which is used for the preparation of the agents according to the invention is, has a mid-late harvest date, a uniform height with a narrower Flowering zone and large flower heads and is therefore particularly suitable for mechanical harvesting suitable In addition, the new tetraploid plants sown at the same time Chamomile generally bloom together practically at the same time, so that too this greatly simplifies and facilitates the harvest.

This new chamomile also has a high yield.

The bisabolol and bisabolol produced according to the invention from this chamomile Compounds rich in chamazulas with anti-inflammatory effects are used, for example, in the Used in medicine, cosmetics and in the form of teas.

Thus, from the dried material obtained according to the invention for example by extraction with alcohols or aqueous alcohol mixtures or by extraction with supercritical gases chamomile extracts or chamomile extracts can be obtained.

Furthermore, chamomile oil, (-) - «-Bisabolol, Chamazulene and other chamomile ingredients can be obtained.

So contain alcoholic extracts of the dry material according to claim 1 at least 1.5 g%, preferably 5.0 mg% chamazulene and at least 5.0 mg%, preferably at least 10.0 mg% (-) - «-bisabolol in the alcoholic drug extract and less than 8 mg% of other bisaboloids.

Such extracts are produced in the usual manner.

For the extraction, for example, mixes in directions, for Example of so-called trough mixers, percolators and other suitable extraction equipment The temperature during the extraction is, for example, 10 up to 500 C. A cooling is not mandatory.

Straight or branched aliphatic, monohydric or polyhydric alcohols with 1 to 6 carbon atoms and solketal (2-dimethyl-4-oxymethyl-1,3-dioxolane) in question, such as methanol, ethanol, propanol (2), butanol, glycerin and similar ones, as well as mixtures of these solvents with water.

Mixtures of these solvents can also be used. the Minimum amount of solvents is 2 parts of solvent to 1 part of the dried Materials. In general, 2 to 20 parts of solvent are used per 1 part of the dried material, in particular 3 to 10 parts of solvent to 1 part of the dried material.

An essential ingredient obtained from the dry material according to claim 1 Oil contains at least 3.5%, preferably at least 5% chamazulene and at least 10%, preferably at least 15% (-) - d-bisabolol and less than 10% of the rest Bisaboloid.

The essential oil is generally made by that the dried material with water, for example in the presence of ascorbic acid (for example as a salt, especially as a sodium salt) at a pH between 4 and 6, preferably 5 to 5.5 heated to the boil. The pH is for example adjusted by means of an acid such as hydrochloric acid.

For example, on 1 part by weight of the dried material 10 to 50 parts by weight of water and optionally 0.1 to 1 part by weight of ascorbic acid used.

It is generally heated for 2 to 8 hours.

The aqueous distillate obtained is several times with a lower aliphatic, liquid hydrocarbon (for example petroleum ether (for example Bp 35 - 600 C), pental, xylene, decalin) shaken out several times, the organic Phase dried (for example using sodium sulfate) and the organic solvent gently removed (for example by distilling off in a rotary evaporator or by distillation at 40-700 ° C., preferably at 50-600 ° C.).

In the case of higher-boiling solvents, this distillation is reduced Vacuum carried out.

The determination of chamazulene is carried out in a similar way by spectrophotometry the usual way with chamomile extracts.

The determination of the (-) - d-bisabolol and the other ingredients of chamomile oil is carried out using the gas chromatographic method customary for this purpose.

Contains a precise description of the analytical methods of determination Appendix A.

The active ingredient chamazulene is not found in chamomile flowers as such, but in the form of the sesquiterpene lactone Matricin. The Matricin has one pharmacological action equivalent to that of chamazulene. From this preliminary stage Matricin is created, for example, when heating (e.g. steam distillation, Tea infusion) immediately chamazulen. It is therefore common not to use the chamomile Content of Matricin, but the analytically ascertainable content of the resulting content Chamazulens to indicate.

Example 1 Obtaining an agent with an anti-inflammatory effect from a diploid parent chamomile: A chamomile that is obtained as follows is described, is sown in the usual manner in the field.

Once the plants have developed and the flower heads are in are at the vegetation stage where about 50% of the tubular flowers are open these flower heads are harvested with a chamomile picking machine, keeping the distance between the combs the picking machine are set so that only the flower heads, their tubular flowers 50% open should be stripped. The crop is delivered to you as quickly as possible shaded place and transported there until further processing in a thin layer spread out. Then the flower heads are in a sieve from the Stalks freed and dried to constant weight. The weight loss is about 80%. Drying takes place in the shade in a well-ventilated place Horde in a layer thickness of about 10 cm.

After about 2 - 3 days, the drying process is complete. To remove Stalk parts and flower grit are sifted and then the dried material pressed into bales.

Analysis of essential oil: 910 mg% Chamazulene: 117 mg% (-) - oL-bisabolol: 252 mg% The initial diploid chamomile used is obtained as follows: By Single plant variability tests of the diploid, little bisabolol-containing, but not bisabolol-free chamomiles, which are described in Franz, Ch., J. Hölzl and A. Vömel: Acta Horticulturae 73, 109-114 (1978), it was found that maximal Up to 20% of all individuals in the essential ö have a chamazulene content of around 20 % By weight and / or have a high (-) - i-bisabolol content of 50% by weight, at the same time the content of the other bisaboloids (especially (-) - Ot-bisabolonoxide) is very low.

These individuals were selected from and tetraploidized as follows: Seeds of the camomile plants selected in this way were diluted with a 0.05% aqueous solution Colchicine solution soaked filter paper applied and at room temperature (200 C) Let it swell for 6 hours. They were then removed from the filter paper, with Rinsed with water several times and sown in seed boxes (greenhouse): Earth: peat-sand mixture 1: 1, temperature: 18 to 200 C, relative humidity: approx. 60%, length of day with artificial light: 14 hours.

The germinating plants were observed up to flowering, the polyploidization success was determined by comparative measurements of pollen and seed sizes and by counting chromosomes of the plants (F1 progeny = first offspring of the colchicinized plants confirmed as tetraploid).

Tetraploidization can also be done in the following ways: On 5 to 7 days old, well developed chamomile seedlings germinated on filter paper soaked in water were after at room temperature (200 C) for 4 to 6 hours with the cotyledons placed below in a 0.05% colchicine solution. The sensitive radicles were spared; in order to avoid drying damage to them, the surrounding Atmosphere have almost 100% relative humidity. After treatment were the seedlings rinsed several times with water and pricked out in plant boxes.

Further treatment was the same as for the seeds.

The pollen size measurements are made with a Leitz binocular research microscope carried out with micrometer measuring eyepiece and micrometer slide.

Chromosome counting takes place on root tips: From those in the greenhouse Young plants that are grown or cuttings become 1 to 2 cm long fresh root ends collected, 5 hours in 0.002 molar hydroxyquinoline solution and then 15 Immersed in 1N HCl for minutes. About 1 mm of the root tips are examined Stained with 2% orcein-acetic acid and examined microscopically in oil immersion.

The cells in mitosis can have 4 times the chromosome set of the somatic cells can be determined (4n = 36).

Those plants in which the pollen diameter is around 50 % larger than that of the diploid starting material (approx. 30 instead of approx. 20 Fm) and where the Set of chromosomes of the somatic cells 36 was doubled (for the diploid starting material is the corresponding number 18) are tetraploid. These were selected out. About 0.1-0.5% of the seeds or the seedlings were tetraploidized in the method given above and developed intact plants capable of flowering. It now close, for example steps 1 and 2.

Step 1: From the tetraploids selected as described above Chamomile plants were selected from those individuals who had a minimum content for chamazulene of 100 mg% and for (-) - d-bisabolol of 200 mg% and their content of other bisaboloids (especially bisabolol oxides) below 50 mg%. All values relate to flower heads that have dried at approx. 400 C. were harvested at the stage when approx. 30 - 70% of all tubular flowers of a head are open.

Step 2: Of the plants obtained after Step 1, all of the The flowers were removed and the plants were placed in a greenhouse and bloomed together in isolated conditions. The plants stood here in 11 cm pots filled with garden soil, at 18 to 240 C daytime and 12 to 140 ° C Night temperature.

The day length was at least 14 hours and was in the winter half-year achieved by additional exposure (200 watts / m2). The water supply took place after Requirement.

From the totality of the selected individuals were over a period of time For seed production, those heads that have faded over a period of 4 weeks are continuously harvested and were about to fall apart. Drying took place in a good ventilated hall with an air temperature between 20 - 300 C; subsequently became the seeds are sifted through a slot sieve (5 x 0.4 mm) and passed through a vertical sifter cleaned afterwards.

The seed obtained after step 2 is the propagation seed of the procedural chamomile.

Flowers of plants from this propagation material (sowing September / October, Harvest at the beginning of June of the following year), which are picked at the time when 30 - 70% of the tubular flowers are open, and then immediately afterwards in the drying cabinet Were dried at 400 C for 72 hours, based on the weight of the dried Flowers, at least 100 mg% chamazulene, at least 200 mg% (-) - oL-bisabolol and at most 50 mg% remaining bisaboloids.

Example 2 Obtaining an anti-inflammatory agent a diploid parent chamomile: a chamomile obtained as follows is described, is sown in the usual manner in the field.

Once the plants have developed and the flower heads are in are at the vegetation stage where about 50% of the tubular flowers are open these flower heads are harvested with a chamomile picking machine, keeping the distance between the combs the picking machine are set so that only the flower heads, their tubular flowers 50% open should be stripped.

The crop is transported to a shady place as quickly as possible and spread out there in a thin layer until further processing. Then be the flower heads freed from the stalks in a sieve and until their weight is constant dried. The weight loss is about 80%. The drying takes place in the shade in a well-ventilated place on shelves with a layer thickness of about 10 cm.

After about 2 - 3 days, the drying process is complete. To remove Stalk parts and flower grit are sifted and then the dried material pressed into bales.

Analysis of essential oil: 1020 mg% Chamazulene: 173 mg% (-) - o (-Bisabolol: 418 mg%.

The initial diploid chamomile used is obtained as follows: By Single plant variability tests of the diploid, little bisabolol-containing, but not bisabolol-free chamomiles, which are described in Franz, Ch., J. Hölzl and A. Vöme: Acta Horticulturae 73, 109-114 (1978), it was found that maximal Up to 20% of all individuals in the essential oil have a chamazulene content of around 20 % By weight and / or have a high (-) - OC bisabolol content of 50% by weight, at the same time the content of the other bisaboloids (especially (-) - OC-bisabolonoxide) is very low.

These individuals were selected from and exactly as in Example 1 indicated is tetraploidized and the tetraploid individuals selected.

About 0.1 to 0.5% of the seeds and the seedlings, respectively, were tetraploidized and developed intact plants capable of flowering.

For example, steps 1 to 6 now follow.

Step 1: From the selected tetraploids (as described above) Chamomile plants were selected those individuals who A) at about the same time bloom, B) a uniform, basic branch and a have a narrow flower zone of approx. 10 cm, preferably 5 cm, C) large flower heads with an outside diameter of approx. 30 mm, preferably 25 - 35 mm, D) achieve a minimum content for chamazulene of 150 mg% and bisabolol of 300 mg% or exceed and their content of other bisaboloids (especially bisabolol oxides) is well below 50 mg%. (All values refer to flower heads, which were dried at 400 C and harvested at the stage where 30 - 70% of all tubular flowers of a flower head are open.

These plants have been cloned. For this purpose, the plants (clone mother plants) first cut back to about 15 cm shoot length, less than 8 to 10 hours day length and 12 to 140 C for new shoots (short side shoots). The short shoots were cut and put in a peat-sand mixture. At around 100% relative humidity, The rooting lasted 15 ° C air temperature and a day length of 14 hours the cuttings 7 to 14 days.

Instead of the specified conventional cloning (cuttings propagation) the in-vitro propagation of divisible parts of the plant's tissue can also be used (so-called meristem propagation). Suitable for establishing a camomile culture different parts of the plant, preferably the shoot tips or the axillary buds.

After rinsing the plants with H202, use aseptic conditions in "Laminar Flow" (high-performance suspended matter Filter with low turbulence Displacement flow) sprout tips of the axillary buds removed and placed in test tubes transferred with a nutrient medium, for example according to Murashige and Skoog (Physiol.Plant. 15, 473-497, 1962) are filled. The test tubes are in a climatic room with 12-18, preferably 16 hours day length (achieved with fluorescent fluorescent tubes), a light intensity of 500-10,000 lux, preferably 1,000-3,000 lux and one Temperature of 15-300 ° C., preferably 22-270 ° C., is set.

Once the explants show good growth, they will be on a the above nutrient medium, but with a higher cytokinin concentration (30 mg / l N6-isopentenyladenine) and little or no auxin (0-0.3 mg / l indole acetic acid) convicted. As a result, the axes stretch and there are adventitious organs as well increased axillary buds formed. These can be removed in the aforementioned manner and be attracted.

The explants intended for plant reproduction in large numbers (the 3rd passage = 3rd generation of reproduction) become after growth and training of the leaves on the first-mentioned nutrient medium transferred to a nutrient medium, which 10 mg / l indole acetic acid or 3-indole butyric acid or 0.1 - 0.3 mg / l i-naphthylacetic acid contains. The plants take root and can be in with after about 4 weeks Sterilized garden soil (steamed for 12 hours at 1200 C) filled pots are planted and in the greenhouse (under conditions as for conventional propagation of cuttings usual) can be further cultivated.

Nutrient medium according to Murashige & Skoog: mg / l mg / l NH4N03 400 indole acetic acid 2.0 Ca (NO3) 2.4H2O 144 Furfuryladenine 0.1 KN03 80 Thiamine 0.1 KH2PO4 12.5 Nicotinic acid 0.5 MgSO4.7H2O 72. Pyridoxine 0.5 KCl 65 Glycine 2.0 NaFe-EDTA 25 myo-Inositol 100 H3BO3 1.6 Casein hydrolyses. 1000 MnSO4. 4H2O 6.5 sucrose 2% ZnS04.7H20 2.7 purified KJ 0.75 agar powder 1% Step 2: The plants obtained after Step 1 bloomed together under isolated conditions in the greenhouse.

The plants were in 11 cm pots filled with garden soil, at 18 to 240 C day and 12 to 140 C night temperature. The day length was at least 14 hours and was achieved in the winter months with additional exposure (200 watts / m2). The water supply was provided as required.

From the totality of the selected individuals were over a period of time For seed production, those heads that have faded over a period of 4 weeks are continuously harvested and were about to fall apart. Drying took place in a well-ventilated Hall with an air temperature between 20 - 300 C; subsequently became the seed sieved by means of a slot sieve (5 x 0.4 mm) and through a vertical sifter cleaned afterwards.

Step 3: The seeds obtained after step 2 became a random sample taken and raised about 2000 offspring (ecological conditions such as selected in step 2) and according to the same criteria A) to D) from step 1. Step 2 was then carried out with the individuals selected in this way.

Step 4: From the seed according to step 3, one part became two sown in different locations in autumn.

Location I) 450 m above sea level, 48.50 N / 11.50 0, 750 mm total annual precipitation, humid-temperate climate, January -10 to 0 ° C, July +10 to + 20 ° C, location II) 200 m above sea level, 420 N / 10 0, 400 mm total annual precipitation, Mediterranean climate, January 0 to + 10 ° C, July +20 to +300 C.

The sowing took place at both locations at the end of September / beginning of October.

The field test stands obtained in this way were homogeneous in terms of Growth, flower size and harvest date checked and assessed (rated), in addition were NN = north sea level = sea level ON = north latitude (ngrad) 00 = easterlings Length (ngrad) Samples of the flowers examined for the active ingredient content.

Those individuals were selected again from the field stock, which correspond to the parameters mentioned in step 1. These become seeds won according to step 2, last sentence.

Step 5: With the seeds according to step 4, steps 3 and 4 repeated in the order and manner shown.

Step 6: From the seeds obtained after step 5, approx 1500 individuals drawn (ecological conditions as in step 2) and after the same principle as indicated in step 1 is selected. From the so selected Plants were selected from 34 individuals and cloned according to step 1. 10 plants each of each clone were randomly distributed at a distance of 40 x 30 cm in the field (location I, see step 4) planted in an isolated location. The soil was loess loam, pH 7.0; the planting took place at the beginning of June, the first harvest of the seeds in mid-July, after that the plants were cut back, bloomed again and delivered mid to A second seed harvest at the end of August.

The seed extraction of this material was carried out according to step 2.

The seeds obtained after step 6 are the propagation material of the so preserved chamomile.

Flowers of plants from this propagation material (sowing September / October, Harvest at the beginning of June of the following year), which are picked at the time if 30 - 70% of the tubular flowers are open, and immediately afterwards were dried in the drying cabinet at 400 72 hours, based on the Weight of the dried flowers (dry matter), for example at least: 150 mg% chamazulene, 300 mg% (-) - O (-Bisabolol and a maximum of 50 mg% other bisaboloids.

Example 3 Production of an essential oil: 200 g according to the invention Dried chamomile flowers obtained (drying was carried out at an air temperature of 500 ° C.) with exclusion of sunlight) are in a 5-liter round bottom flask with 3.6 liters Water and 2 g of sodium ascorbate are added and the mixture is adjusted to pH 5.0 with 1 N HCl set. After adding boiling stones, the mixture is heated to boiling. Within approx. 1.2 liters of distillate are collected for approx. 3 hours.

After the distillation has ended, the distillate is three times with 100 ml of petroleum ether extracted and dried over anhydrous sodium sulfate. the The dried solution is filtered and the solvent is then used in a rotary evaporator distilled off. The yield is 1.44 g of essential oil.

In the obtained essential oil, the content of chamazulene is then determined and (-) - <-Bisabolol determined. Appendix A Extraction of the Essential bls starting material is a dried material from a chamomile, which according to the invention for the preparation of the anti-inflammatory agent comes into question.

Only those flower heads are used to make the oil, in which 30 to 70%, in particular 40 to 60% of the tubular flowers are open. Drying takes place in a drying cabinet at 400 ° C. for 72 hours.

Chamomile flower essential oil is described as follows Obtained by steam distilling the dried material for two hours: 2.0 g of whole, dried flowers are placed in a 250 liter round bottom flask ml of deionized water and a two-hour reflux distillation in one Clevenger apparatus (steam distillation reflux apparatus for gravimetric Determination of small amounts of essential oils). 1 ml of pentane is used as a template per analysi. The return speed is 40 + 4 drops / minute. After completion the essential oil dissolved in pentane becomes as anhydrous as possible in the distillation Test tubes drained and any residual essentials in the apparatus Rinsed oil with pentane. The solution is used to remove any water residues Add a spatula tip of dried Na2SO4 and then pour the solution through a glass funnel with porosity D 3 or D 4 is sucked off in a crimp-top bottle. After evaporation of the pentane at 40 ° C in a water bath and drying in a desiccator the amount of oil is determined gravimetrically.

The chamazulene is then added to the oil obtained in this way (approx. 20 mg) and the bisabolol determined.

Spectral botometric determination of Chamazulens Measurement solution: The entire, Essential oil (about 20 mg) obtained from 2 g of the dried material (obtained as described above) is dissolved in 25 ml of n-hexane or cyclohexane.

Measuring device: filter photometer (e.g. Eppendorf).

Wavelength: 578 nm. Cuvette: 1 cm. Specific absorbance of chamazulene (1 g / 100 ml; 1 cm): 20.8 Compensation liquid: n-hexane or cyclohexane Founder Chamazulene content in mg / 100 g: 120 E578 If there is no filter photometer for measurements available, the determination can also be carried out with a spectrophotometer are: measuring device: spectrophotometer (for example PM Q II / or PM Q III "ZEISS") Wavelength: 605 nm. Cuvette: 1 cm Specific absorbance of chamazulene (1 g / 100 ml; 1 cm): 24.5 Compensation liquid: n-hexane or cyclohexane Founder Chamazulene content in mg / 100 g: 102 E605 In the test solution, the Bisabolol determined.

Gas chromatographic determination of bisabolol and the other bisaboloids Gas chromatograph: Hewlett Packard model 5750, Erba Fractovap 2350 or similar Device Detector: Flame Ionization Detector Carrier Gas: Helium Column: 1/8 inch; 200 cm; Steel column filling: 3% nitrile silicone rubber "XE 60" silanized on kieselguhr "Chromosorb WAW HP" 125 to 150 Fm as carrier material Temperature: Detector: 320 ° C injection block: 2200 C column: 85 - 220 ° C temperature programming: 4 ° / minute Sample solution: The measurement solution for Chamazulen is used. Approx. 15 mg of standard bisabolol are dissolved in 25 ml cyclohexane Injection quantity: 5 l of sample solution and comparison solution each. Evaluation: The evaluation is carried out by Pe akf I compare surfaces Bisabolol content in mg per 100 g dried flowers: 10 x weight (comparison) / mg T x area (sample) area (comparison) The other bisaboloids can also be determined by gas chromatography, For example, take place under the following recording conditions: Devices: Packard, model 7721, series 800 or Erba Fractovap series 2350 columns: glass columns, 3 m / 2 mm in diameter; 2 m / 2 mm in diameter Filling: 3% methylphenyl silicone rubber "OV 1" silanized on kieselguhr "Gaschrom Q" 125 to 150 µm as carrier material Carrier gas: 30 ml / minute N2 temperature program: 80 to 1800 C, 2.5 (31 ° C / minute Injector / detector temperature: 2000 C Detector: Flame ionization detector Injection quantity: approx. 2 ßl of the approx. 1:50 diluted essential oil The evaluation is partly carried out without, partly with an internal standard. Methyl laurate is suitable as an internal standard or hexadecane for wise chamazule-free Oils. For oils with a chamazulene content above 5%, this is the internal standard preferable, the content being determined photometrically (at 578 nm).

Claims (6)

Process for the preparation of a new agent with anti-inflammatory Effect claims: 1. Method for obtaining funds with anti-inflammatory Action from Matricaria Chamomilla, characterized in that one has a diploid Chamomile, in which (-) - d-bisabolol is the main component of the essential oil, tetraploidized, selected the tetraploid plants obtained, now from these tetraploid plants selected those plants whose dried at 400 C. Flowers at least 100 mg% chamazulene, at least 200 mg% (-) - «-Bisabolol and less contain more than 50 mg% of other bisaboloids, and of the so obtained Plants, optionally after further selection and propagation steps, the Flowers in the vegetation stage where 30-100% of the tubular florets of a flower head are open, harvested and dried at a temperature not exceeding 70 "C to a Obtain dry material that contains at least 30 mg% chamazulene, at least 100 contains mg & (-) - O (-Bisabolol and less than 50 mg% of other bisaboloids, and optionally from the dry material thus obtained by distillation in The presence of water produces an essential oil that contains at least 3.5% chamazulene, contains at least 10% (-) - QL-bisabolol and less than 10% of other bisaboloids, or an alcoholic chamomile extract by extraction with lower alcohols produces at least 1.5 mgE chamazulene, at least 5.0 mg% (-) - O (-Bisabolol and contains less than 10 mg% of remaining bisaboloids. 2. The method according to claim 1, characterized in that the tetraploidization by means of chemicals at temperatures between 0 and 350 C, by means of gamma rays, X-rays or UV rays at temperatures between 0 and 350 C, by means of high temperatures from 33 to 50 ° C or by means of low temperatures from 0 to 50 C takes place. 3. The method according to one or more of the preceding claims, characterized in that the flowers are harvested at the vegetation stage where 30 - 70% of the tubular flowers of a flower head are open and the flowers be dried at an air temperature not higher than 50 ° C and that way Dried material obtained at least 100 mg% Chamazuen, at least 200 mg% (-) - Ot-Bisabolol and contains less than 50 mg% of other bisaboloids, and a if necessary, essential oil produced therefrom at least 3.5% chamazulene, at least 10% (-) - d-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from it at least 5.0 mg% chamazulene, at least Contains 10.0 mg% (-) - CC-bisabolol and less than 10.0 mg% of other bisaboloids. 4. The method according to one or more of the preceding claims, characterized in that the flowers are harvested at the vegetation stage where 30 - 70% of the tubular flowers of a flower head are open and the flowers be dried at an air temperature between 50 to 700 C and the resultant dried material at least 50 mg% chamazulene, at least 150 mg% (-) - d-bisabolol and contains less than 50 mg% of remaining bisaboloids, and optionally one thereof Manufactured essential oil at least 3.5% chamzulene, at least 10% (-) - OC-bisabolol and less than 10% of remaining bisaboloids and an alcoholic one made from them Extract at least 2.5 mg% chamazulene, at least 7.5 mg% (-) - oL-bisabolol and contains less than 10.0 mg% of remaining bisaboloids. 5. The method according to one or more of the preceding claims, characterized in that the flowers are harvested at the vegetation stage where 70 - 100% of the tubular flowers of a flower head are open and the flowers be dried at an air temperature not higher than 500 C and so Dried material obtained at least 40 mg% chamazulene, at least 120 mg% contains (-) - d-bisabolol and less than 50 mg% of other bisaboloids, and a if necessary, essential oil produced therefrom at least 3.5% chamazulene, at least 10% (-) - ot-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from it at least 2.0 mg% chamazulene, at least Contains 6.0 mg% (-) - OL-bisabolol and less than 10.0 mg% of other bisaboloids. 6. The method according to one or more of the preceding claims, characterized in that the flowers are harvested at the vegetation stage where 70 - 100% of the tubular flowers of a flower head are open and the flowers be dried at an air temperature between 50 - 700 C and the resultant dried material at least 30 mg% chamazulene, at least 100 mg% (-) - d-bisabolol and less than 50 mg% of the rest Contains bisaboloids, and a any essential oil produced from it, at least 3.5% chamazulene, at least 10% (-) - α-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from it at least 1.5 mg% chamazulene, at least 10 mg% (-) - O (-Bisabolol and less than 10.0 mg% of other bisaboloids contains.