CH671674A5 - - Google Patents

Description

DESCRIPTION

Preparations of the flower heads of chamomile (Chamomilla recutita (L.) Rauschert, synonymous with Matrica-ria chamomilla L.) are widely used in therapy because of their anti-inflammatory and spasmolytic effects and form an important part of the herbal medicinal product. The active ingredients (-) - a-bisabolol and chamazulen are of particular therapeutic importance. A good chamomile drug should therefore have the highest possible content of these two substances.

The naturally occurring diploid chamomiles are very heterogeneous in terms of their active ingredient content. In particular, only one of the most important active ingredients chamazulen and (-) - a-bisabolol is present, or these two active ingredients are completely absent or occur together only in very small amounts, in which case the main component of the essential oil from the less effective bisaboloids ( Bisabolonoxid A or B, Bisabololoxid A) exists.

Under the name DEGUMILL (this is the chamomile variety mentioned in the claim of the German patent specification 2 402 802; GDR variety protection right Degumill; Italian patent 1 035 096) a chamomile variety is known which also has a high content of (-) - a-bisabolol and chamazulen. However, the chamazule and bisabolol content of this chamomile variety DEGUMILL is only stable if any cross-breeding or cross-pollination with other chamomile varieties whose bisabolol and chamazule content is considerably lower, or with the wild camomile low in active ingredients, is prevented. This risk of cross-breeding through cross-pollination is almost always present, as wild chamomile occurs practically everywhere.

Various tetraploid chamomile types are also known (for example BODEGOLD, DDR; POHORE-LICKY, CSSR; ZLOTY LAN, Poland; BK-2, Hungary). Although these tetraploid chamomile varieties have a satisfactory chamazule content, the important active ingredient (-) - a-bisabolol is only present in extremely small amounts in these known tetraploid chamomile varieties, and the other bisaboloids (bisabolol oxide A and B and bisabolone oxide) prevail instead ), which together make up more than half of the essential oil in the well-known tetraploid chamomile varieties.

■ It has now been found that, quite generally, bisabolol-rich tetraploid chamomile plants can be obtained from naturally occurring camomile populations or diploid or tetraploid camomile cultivars by certain treatment or procedural steps, which on the one hand are no longer susceptible to cross-pollination with naturally occurring camomiles and on the other hand have at the same time a high content of chamazulene and (-) - a-bisabolol, the content of (-) - a-bis-abolol considerably exceeding the chamazulene content, and at the same time the other bisaboloids occur practically not or only in very small amounts. It is therefore essential that the high content of the main active ingredients (-) - a-bisabolol and chamazulene is constant in the chamomile according to the invention, that is to say it is retained with every propagation.

The invention relates to the objects or facts defined by the claims, in particular a method for producing a new tetraploid chamomile with advantageous and improved properties.

The new tetraploid chamomile according to the process is surprisingly distinguished from the previously known camomiles or chamomile types by a number of new and advantageous properties. In particular, it is no longer susceptible to cross-pollination with the naturally occurring chamomile populations (wild chamomile) like the well-known chamomile variety DEGUMILL. Compared to the other known diploid chamomiles and tetraploid chamomile varieties, the chamomile according to the process surprisingly differs by a higher content of the important active ingredient (-) - a-bis-abolol (at least 200 mg%), while the content of the other bisaboloids (e.g. bisabolol oxides ) is very low and is less than 50 mg%. For example, the well-known chamomile varieties described in the literature all have a very high content of bisabolol oxides and partly bisabolon oxide, which usually accounts for approx. 50% of the essential oil of the drug (i.e. at 1% essential oil content approx. 500 mg per 100 g drug).

Furthermore, in contrast to the previously known tetraploid chamomile varieties, the chamomile according to the invention is homogeneous in terms of content, the properties being resistant to chamazulen and (-) -a-bisabolol (ie homozygous).

In contrast, the single plant test of the well-known tetraploid chamomile varieties shows that the individual individuals can be assigned to different types of ingredients, i.e. every sample of a drug produced from it

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provides a qualitatively and quantitatively different, inhomogeneous result.

In addition, the chamomile obtained according to the invention surprisingly differs from the known tetraploid chamomile varieties, for example, by one or more of the following properties: improved germination capacity of the seeds, less accumulation of unusable herb mass (ie higher flower yield); lower water content of the flowers (that means better yield of dried flowers and shorter drying times); better suitability for mechanical harvesting because the flowers are largely localized in one plane and most flowers bloom at the same time (this also enables a uniform harvest date); better shelf life of the drug (less tendency to decay and horror formation); particularly aromatic and typical camomile scent.

The last-mentioned advantages occur, for example, if, in addition to the active ingredient content, selection is made for one or more of the abovementioned characteristics, seed is obtained from the selected plants, is selected again from the progeny derived therefrom and this measure is repeated 3-5 times .

The object of the invention is the production of a new tetraploid chamomile with improved properties, in particular an increased content of (-) - a-bisabolol.

The present invention accordingly relates to the methods and products defined in the claims.

The following diploid camomiles are for example: "Chamomile of Argentinian provenance" (see LZ Pa-dula, RVD Rondina and JD Coussio, Quantitative Determination of Essential Oil, Total Azulenes and Chamazu-lene 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 of (-) - <z-bisabolol (generally over 5% of the essential oil) in the essential oil. For example, such diploid chamomiles come into question, which are described in the following literature references: Schilcher, H. “Recent findings in the quality assessment of chamomile oil or chamomile flowers”, Planta med. 23, 132-144 (1973); Moti, O., M. Felklovâ, V. Lukes & M. Jasicovâ “For gas chromatographic analysis and chemical types of chamomile oil”, Arch. Pharm. 310, 210-215 (1977);

Franz, Ch., J. Hölzl & A. Vömel "Preliminary Morphologi-cal and Chemical Characterization of some Populations and Varieties of Matricaria chamomilla L.", Acta Hort. 73: 109-114 (1978).

The camomile essential oil usually consists of the main components Farnesen, Spathulenol, Chamazulen one of the 4 bisaboloids ((-) - a-Bisabolol, Bisabololoxid A, Bisabololoxid B or Bisabolonoxid, as far as it concerns diploid single plants; in the mixed sample of the population as well In tetraploid individuals, several bisaboloids can be contained side by side) as well as from spiro ethers. The above-mentioned substances usually make up 70 - 80% of the essential oil. Therefore, diploid camomiles are particularly suitable, where (-) - a-bisabolol is the predominant component (more than half of the sum of the aforementioned substances). Diplomatic camomiles are particularly suitable as starting camomiles, in which, for example, the (-) - a-bisabolol represents at least 40% of the essential oil or at least 90% of the bisaboloids.

In particular, such diploid and chamomile populations come into consideration, which in the mixed drug sample generally have at least 100 mg% chamazulen and 50-100 mg% (-) - a-bisabolol (based on the dry matter of the flowers dried at 40; C) In other words, in the case of a diploid camomile, seed is obtained from such camomile populations and this seed is tetraploidized (without taking into account and / or knowledge of the bisabolol content of the parent plants).

The appropriate diploid camomiles are selected by single plant examinations. In general, it is necessary to examine, for example, 1,000-10,000 individuals from a starting population to find some individuals that have a high (-) - a-bis-abolol content according to the criteria given above and are suitable as starting chamomile. Seeds are then obtained from such selected individuals in the usual way and tetraploidized. After the tetraploidization has been completed, the tetraploid plants are selected from the other plants which have remained diploid. From the tetraploid plants obtained in this way, if appropriate after previous propagation, all those plants are now selected whose flowers dried at 40 ° C. contain at least 100 mg% chamazulen, at least 200 mg% (-) - a-bisabolol and less than 50 mg% other bisaboloids included. These flowers are harvested at the stage of development where 30 - 70% of all tubular flowers of the flower head are open. If necessary, this can be followed by further selection and propagation steps, which, for example, improve the following characteristics or properties: Simultaneous flowering, uniform basic branching and narrow flowering zone (i.e. better suitability for mechanical harvesting), large flower heads, better durability the drug, especially aromatic smell.

A particularly advantageous chamomile is obtained if, in the selection according to the chamazulene and (-) - a-bisabolol content, those plants are selected whose chamazulene content is at least 200 mg%, preferably 250 mg% and their (-) - ot-bisabolol content is at least 300 mg, preferably 400 mg% (content of other bisaboloids always below 50 mg%).

The tetraploidization can be carried out, for example, in a manner known per se by treating plant parts (seeds, roots, shoot tips, germs, armpit buds) or tissues of the diploid starting chamomile plants with chemicals, X-rays, gamma rays or UV rays. It can also be carried out by the decapitation callus method, by anther culture or by applying high or low temperatures to the chamomile plants or parts of plants or tissues of the chamomile plants. For example, reference is made to Werner Gottschalk's book "The importance of polyploidy for the evolution of plants", Gustav Fischer Verlag, Stuttgart, 1976, in particular pages 13 to 22.

Chemical tetraploidization.

Examples of suitable chemicals for tetraploidization are: colchicine, acenaphthene, alkaloids such as atropine, veratrine, nicotine, sanguinarine, derivatives of benzene, diphenyl and phenanthrene, naphthalene and naphthalene derivatives, diphenylamine, tribromaniline, paradichlorobenzene, methylnaphthonone, methylnaphthonone, methylnaphthonone, methylnaphthonone, methylnaphthonone , Salicylic acid and related substances, hexachlorohexane, methamphetamine (hydrochloride), alkyl alkali carbamates such as isopropyl sodium carbamate, phenyl urethane, salts of cocodylic acid (for example sodium salt), glycosides from Convallaria such as convonarin, convallatoxin and conva- vallamarin. Heteroauxin, Gemrisan (Phenylmercuribrenzka-techin), organic mercury compounds such as ethyl mercury phosphate, ethyl mercury chloride, phenyl mercury hydroxide. Phenyl mercury dinaphthyl methane disulfonate. Chloroform, nitrous oxide (N; 0) and mixtures

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of these substances. Oil cakes, compost and cow manure are also considered.

The treatment with the substances mentioned here takes place, for example, at temperatures between 0 and 35 ° C., preferably between 12 and 30 ° C., in particular 15 and 25 ° C.

The application is carried out, for example, by treating seeds, shoot tips, roots (in particular root tips or roots of seedlings), ovaries, cut surfaces on leaves or stems, cell suspensions from meristem tissue, callus cultures or also by injection into the basal stem region or in the Area of armpit buds. The chemicals are generally used in the form of solutions in water, weakly alcoholic (alcohol content usually below 5%) or weakly acidic solutions. The pH of the weakly acidic solutions is, for example, 5.5-6.5, the acidification taking place, for example, using lower organic aliphatic acids such as acetic acid. If alcoholic solutions are used, they can 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 are used as such, optionally under pressure (for example 1 to 10 bar). The treatment time is, for example, 1 to 36, preferably 2 to 12, in particular 4 to 6 hours.

The most effective concentrations and the duration of exposure should be tested in preliminary experiments.

For example, treatment with colchicine at temperatures between 0 and 35 ° C., preferably 12 to 30 ° C., in particular 15 to 25 ° C., is particularly favorable. This can be done, for example, by swelling seeds of the starting diploid chamomile in a 0.01 to 0.2%, in particular 0.02 to 0.1, preferably 0.05% colchicine solution, or by germinating, 5 up to 7 days old well-developed seedlings of the diploid starting chamomile (with the cotyledons down) are immersed in a 0.01 to 0.2%, in particular 0.02 to 0.1%, preferably 0.05%, colchicine solution. In the latter method, 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, an exposure time of up to 10 hours is generally sufficient. When using seeds, the duration of exposure may extend up to 36 hours.

After treatment with the chemicals, the swollen seeds, seedlings, or other parts of plants are rinsed several times with water. The swollen seeds are sown, for example. The plants with treated roots or other parts of plants or the treated seedlings are pricked out in plant boxes, for example. The plants are grown from the seeds or seedlings treated in this way (for example in a greenhouse: temperature between 18 to 25 ° C. during the day and 10 to 16 ° C. at night) and the plants selected whose pollen are about 1 '/ linai larger than that Have pollen of the starting material or a chromosome number of 36 somatic cells. If other parts of plants (above or below ground) are subjected to chemical treatment, only the shoots, roots or flowers / seeds resulting from the treated parts are subjected to a later examination for tetraploidization. If, for example, sprout treatment or armpit treatment has been carried out, only the armpit from this armpit will subsequently be used

new shoots emerging from this shoot and the flowers or seeds formed on it were examined for chromosome numbers.

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

Tetraploidization by rays.

The action takes place, for example, on seeds or root tips at temperatures between 0 and 35 ° C., preferably 10 and 30 ° C., in particular 15 to 25 ° C. Irradiation sum: 5 to 50 Krad. Gamma * or X-rays are preferred.

Suitable UV rays are, for example, those with a wavelength of 400 to 30 nm, preferably of 350 nm.

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

Use of high and low temperatures.

As high temperatures, for example, temperatures between 33 and 50 ° C, preferably 42 to 45 ° C in question. For example, these temperatures are exposed to: swollen seeds, seedlings, shoot tips and meristatic tissues. Duration of treatment: for example 1 to 48, preferably 12 to 24 hours.

Possible low temperatures are, for example: 0 to 5 ° C., preferably 0.5 to 4 ° C., in particular 2 ° C. For example, these temperatures are exposed to 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 treated as well as after the treatment with chemicals.

The decapitating callus method (decapitating = decapitation or relaxation or cutting back).

The decapitation is carried out, for example, on young plants on the stem, preferably on the top vegetation cone, after the formation of 4 to 6 leaves or also on petioles or side shoots. The buds or shoots arising from the wound tissue (callus tissue) are cut off, brought to rooting, further cultivated in pots and the tetraploidized plants are selected in the same way as in the chemical treatment.

Anther culture (production of plants with a simple set of chromosomes from the anthers with subsequent spontaneous or artificial tetraploidization).

Closed tubular flowers are harvested from flowering plants, their anthers (anthers) are in the stage before the first pollen mitosis. The anthers are removed from the flower buds using a micromanipulator and transferred to Petri dishes, which are filled, for example, with the nutrient medium according to Nitsch and Nitsch (Table 1). The Petri dishes are then stored in a culture room for 16 hours a day at 28 ° C day and 20 ° C night temperature. After about four weeks, the anthers start to break open and plants grow out. These are haploid in the diploid parent and dihaploid in the te-traploid parent; After roots have formed, they are potted in garden soil, for example, and made to bloom in the greenhouse. These (di) haploid plants are sterile, but can be treated with shoot tips, roots or stems with chemicals such as

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Example colchicine are polyploidized, producing homozygous plants which can then be propagated via seeds. For further procedures, see the treatment with chemicals (for example colchicine treatment).

Table 1

Culture medium according to Nitsch and Nitsch (Science, 1969)

mg / 1

KNOj 950

NH4NO3 720

MgS04 x 7 H20 185

CaCl2 166

KH2PO4 68

MnS04x4H20 25

H3BO3 10

ZnS04x7H20 10

Na2Mo04x2H20 0.25

CuS04 x 5 H20 0.025 5 ml of a solution of 7.45 g of ethylenediaminetetraacetic acid disodium salt and 5.57 g of FeS04 x 7 HzO per 1000 ml of 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-made medium (DIFCO-Bacto agar) 8 g

Indole acetic acid 0.1

pH of the medium adjusted to 5.5

From the tetraploid chamomile plants selected by pollen size measurement and / or chromosome counting, which can be obtained in the ways described above, the plants are then selected which have a minimum chamazule content of 100 mg% and a minimum bisabolol content of 200 mg% during the The content of other bisaboloids (especially bisabolol oxides) should be less than 50 mg% (based on the dried flowers, see Example 1).

The plants selected in this way are allowed to bloom in the greenhouse at 18-24 ° C. day and 12-14 ° C. night temperature and a day length of at least 14 hours after removal of all flower heads which have already blossomed, all flower heads being exposed over a period of 4 weeks have faded or are about to disintegrate, are harvested for seed production. After drying at an air temperature between 20-35 ° C., the propagation material of the chamomile according to the invention is obtained, for example.

The following can also be used as further criteria for this selection:

a) approximately simultaneous flowering,

b) a uniform, basic branching and a narrow flowering zone of approximately 10, in particular 5 cm,

c) large flower heads with an outer diameter of approximately 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 mechanical harvesting.

In order to obtain a chamomile which, in addition to a content of at least 100 mg% chamazulen and at least 200 mg% (-) - a-bisabolol (based on the dried

Flower heads) also has a high flower yield and is more suitable for mechanical harvesting, the following procedure is recommended: The selected plants (as described above) are propagated vegetatively by cuttings and read out over 3 to 5 generations, the selection always according to the above specified criterion and, if applicable, the additional criteria a) - c). The plants selected according to these criteria are cloned, seeds are obtained from the cloned plants, the plants obtained therefrom are again selected according to the minimum content of chamazulene and bisabolol indicated above and, if appropriate, the additional criteria a) -c), and seeds are again obtained from the latter.

The seeding sequence - selection according to the above-mentioned minimum chamazule content of 100 mg% and (-) - a-bisabolol of at least 200 mg% (other bisaboloids below 50 mg%) as well as, if applicable, the additional criteria a) —c) - seed production Repeat 3-5 times.

This is followed by another seeding sequence - as previously specified selection (if necessary cloning) - seed extraction. -

The last seed obtained is the propagation material of the chamomile according to the invention.

The propagation of cuttings takes place in the following way: For propagation of cuttings, the starting plants (mother plants) must form short buds under short day conditions. This takes place in the winter half-year in the greenhouse without additional lighting or in climatic chambers with a day length of 6 to 10, preferably 8 hours and temperatures of 10 to 15 ° C, preferably 12 ° C. Leaf, shoot and in particular short shoot (side shoot) cuttings are suitable for cloning or propagation. They are rooted at 12 to 18 ° C, preferably 15 ° C and day lengths of 12 to 16, preferably 14 hours in a tense atmosphere (approx. 100% relative air humidity). For example, a peat-sand mixture in a ratio of 1: 1 can be used as the substrate; but pure quartz sand, rock wool cuttings cubes, peat cuttings cubes and the like are also suitable.

The following soils are suitable for sowing, for example: garden soil; humic, medium-heavy loam 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 24 ° C., in particular 18 to 20 ° C. If sowing is carried out outdoors, it is preferable to sow in autumn (September / October) or in spring (March / April). These dates apply to all eligible growing areas (e.g. northern hemisphere, temperate to subtropical climates).

The new, procedural chamomile belongs to the cultivated plant species of the real chamomile with the botanical name Matricaria Chamomilla L. (synonym Chamomilla re-cutita (L.), Rauschert) and is defined by the active ingredient information of claim 1. The values given for the active substance contents of chamazulene, (-) - a-bisabolol and bisabolol oxides each refer to the flower development stage that is reached when 30 to 70%, in particular 40 to 60%, of all tubular flowers of a flower head are open (that at this point the flowers used for the determination of the active ingredient were picked and then dried in a drying cabinet at 40 ° C. for 72 hours).

If the chamomile flowers are harvested at a point in time at which the flower development stage has progressed, that is, for example where 100% or until s

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100% of all tubular flowers of a flower head are open (e.g. stage of full bloom) and / or if the harvested flowers are dried at a temperature higher than 40 C, the content of the active ingredients (-) - a-bisabolol and chamazulen may be lower , because higher drying temperatures and / or later harvesting can lead to more degradation of the azulene and bisabol oil.

The term “other bisaboloids” in claim 1 means in particular:

(-) - a-Bisabolol oxide A and B; (-) - a-bisabolone oxide A; Other constituents of the essential oil of the process-like chamomile variety are en-in-dicycloether, Farnesen, Spathulenol and in various concentrations various volatile terpene hydrocarbons.

For example, the flowers of the process chamomile, dried in the drying cabinet at 40 "C (harvested as stated above), contain between 100 to 200 mg% chamazulen, between 200 to 450 mg% (-) - a-bisabolol and only a little, that is to say between 5 to 50 mg% of other bisaboloids based on the dry matter (that is, based on the absolute dry weight of the flowers) This absolute dry weight is obtained by drying a separate sample of chamomile flowers from the chamomile according to the method in a drying cabinet at 105 ° C. to constant weight (72 to 96 The active substance content of the flowers (drug) dried at, for example, 35 to 50 ° C. is then calculated on the basis of the dry mass of the flowers determined at 105 ° C.

In terms of its phenotype, the chamomile according to the process is similar to the hitherto known tetraploid chamomile varieties (for example Bodegold, Zloty Lan, BK-2, Pohorelicky Velkokvety); It differs from these in particular in that the process component of chamomile (-) - a-bis-abolol is the main component of the essential oil of the flowers and that the content of the other bisaboloids (bisabolol oxides A and B; bisabolone oxide) is considerably lower . Other components of chamomile essential oil are Farnese, Spathulenol and En-In-Dicyclo-ether.

The methodical chamomile can be successfully grown on all soils with the exception of soils with a content of more than 20% of organic matter (humus substances and soil organisms); no special agrotechnical processes or cultural measures are required; Only a long day with a maximum day length of more than 13 hours is necessary for cultivation, which means that the temperate zones and subtropics are particularly suitable for cultivation.

The chamomile according to the method often has the following additional advantages: high yield, medium-late harvest date, uniform height with a narrow flowering zone and large flower heads; therefore particularly suitable for mechanical harvesting. In addition, plants sown at the same time generally bloom together practically at the same time, so that this also makes harvesting much easier and easier.

The last-mentioned advantages occur when the following process conditions are used: Of the tetraploid chamomile plants, which have a minimum chamazule content of 100 mg% and (-) -cc-bisabolole of 200 mg%, while the content of other bisaboloids (especially bisabolol oxides) is below 50 mg% (all values based on the dried flower heads), only those are selected which

- bloom at about the same time,

- A uniform basic branching and a narrow flowering zone of approx. 10 cm as well

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- have large flower heads with an outside diameter of approx. 30 mm.

The selected plants are propagated vegetatively via cuttings and read out over 3 - 5 generations, whereby the selection is always made according to the criteria mentioned above. The selected plants are vegetatively propagated (cloned), left to flower together, and the seeds are obtained therefrom. The plants obtained from the seeds are again selected according to the criteria given above and the sequence sowing-selection-seed extraction-sowing is repeated 3-5 times.

A drug produced from the chamomile according to the process contains the maximum content of the active ingredients chamazulen and (-) - a-bisabolol when the chamomile flower heads are harvested at the vegetation stage, where, for example, 30 to 70%, preferably 40 to 60%, that is generally 50% of the tubular flowers of a flower head are open and drying takes place at an air temperature of at most 50 = C, for example 35 to 50 C, in particular 40 C.

Drying can take place either by artificial air supply or also by drying in the shade, possibly also in the sun, but care should be taken to ensure that the heat supply does not go beyond what is necessary for complete drying. It is therefore advantageous to make sure of the weight consistency achieved through check weighing. Drying can be spontaneous or artificial (for example with artificial warm air). The active ingredient yield is greatest in the case of spontaneous drying in the absence of sunlight, preferably at 40-60 ° C., in particular 40-50 C. The drying process should take place as soon as possible or immediately after the harvest. The drying should be carried out in thin layers, for example from 5 to 20 cm, preferably 10 cm thick. Drying is also possible, for example, in well-ventilated halls with an air temperature between 20—30 = C. In general, the air temperature for drying should not be higher than 60 ° C. For example, an air temperature between 35 and 50 ° C is favorable.

The active substance content of a drug produced from the chamomile according to the invention, in particular of the main active substances chamazulen and (-) - a-bisabolol, depends on the vegetation stage in which the flowers are at the time of harvest and on the drying of the harvested flowers. The higher the drying temperature, the greater the breakdown of the active ingredients, that is, the lower the content of the dried flowers in the active ingredients. For the same reason, direct sunlight has an adverse effect on drying and should be avoided if possible.

The vegetation stage of a flower is characterized by what% of the tubular flowers of a flower head are open at a certain time (here the time of harvest). Flowers can therefore be harvested where, for example, between 30-50%, 30-70%, 40-60%, 60-100% or 90-100% of the tubular flowers of a head are open; The active substance content depends on the stage in which the flowers are and it is greatest in the chamomile according to the invention when 40-60% of all tubular flowers are open and it is lower both with fewer and more open tubular flowers of a flower head.

It is therefore a major advantage of the chamomile according to the invention that the individual plants are flowered uniformly, that is to say that the majority of the plants from a sowing have the same flowering stage, that is to say, for example, at

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the vast majority of plants 40 - 60% of all tubular flowers of a flower head are open at the same time. As a result, in particular in the case of the chamomile according to the invention, a complete detection of the flower heads at the optimum time is possible, and the chamomile according to the invention is therefore particularly suitable for mechanical harvesting.

Drying temperature (air temperature)

not higher than 50; C

not higher than 50 ° C

between 50-70 ~ C

between 50-70 ° C

From this it follows that from the chamomile used to produce the agents according to the invention, for example during a harvest which takes place in the vegetation stage, where between 30-100% of the tubular flowers of the flower heads are open and are dried at air temperatures up to 70 ° C. a dry material is obtained, the chamazulene content of which is at least 30 mg% and the (-) - a-bisabolol content of at least 100 mg%, while the content of other bisaboloids is always less than 50 mg%.

In the alcoholic extracts, the content of other bisaboloids is always less than 10 mg%.

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

Chamazulen is determined spectrophotometrically in a manner similar to that used for chamomile extracts.

The (-) - a-bisabolol and the other ingredients of chamomile oil are determined using the gas chromatographic method that is customary for this purpose.

Appendix A contains a detailed description of the analytical methods of determination.

The active ingredient chamazulen is not in the chamomile flowers as such, but in the form of sesquiterpene lactone

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The relationship between the content of chamazulene and (-) - a-bisabolol, on the one hand, with the flowering stage at the time of harvest and, on the other hand, with the drying temperature during drug production is shown in Table 5 below (the content of other bisaboloids is less than 50 in all cases) %).

Matricin before. Matricin has a pharmacological effect similar to that of chamazulen. From this preliminary stage, Matricin, for example, the chamazulen immediately arises during heating (e.g. steam distillation, tea infusion). It is therefore customary not to indicate the content of matricin in chamomile, but the content of the chamazulen formed from it.

Possible uses of the Ka-50 mille according to the invention are, for example: extraction of chamomile drug, chamomile oil, chamomile extracts and (-) - cc-bisabolol, chamazulen and other chamomile ingredients.

For example, chamomile extracts or chamomile extracts can be obtained from the drug obtained from the chamomile according to the invention, for example by extraction 55 with alcohols or aqueous alcohol mixtures or by extraction with supercritical gases. Furthermore, chamomile oil, (-) -ct-bisabolol, chamazulen and other chamomile ingredients can be obtained from the drug.

Alcoholic extracts of the drug contain, for example, at least 1.5 mg%, preferably 5.0 mg% chamazulen and at least 5.0 mg%, preferably at least 10 mg% 65 (-) - a-bisabolol in the alcoholic drug extract and less than 8 mg% on other bisaboloids.

Such extracts are produced in the usual way.

Vegetation stage of the flowers at the time of harvest

30-70% of all tubular flowers of a flower- 70-100% of all tubular flowers of a flower head open head open

Active substance content in the dried

Material:

Chamazulen:

at least 100 mg%

(-) - a-Bisabolol:

at least 200 mg%

Active substance content in alcoholic

Abstract:

Chamazulen:

at least 5.0 mg%

(-) - a-Bisabolol:

at least 10.0 mg%

Active substance content in the dried

Material:

Chamazulen:

at least 50 mg%

(-) - cc-bisabolol:

at least 150 mg%

Active substance content in alcoholic

Abstract:

Chamazulen:

at least 2.5 mg%

(-) - a-Bisabolol:

at least 7.5 mg%

Active substance content in the dried material:

Chamazulen:

at least 40 mg%

(-) - a-Bisabolol:

at least 120 mg%

Active substance content in the alcoholic extract:

Chamazulen:

at least 2.0 mg%

(-) - a-Bisabolol:

at least 6.0 mg%

Active substance content in the dried material:

Chamazulen:

at least 30 mg%

(-) - a-Bisabolol:

at least 100 mg%

Active substance content in the alcoholic extract:

Chamazulen:

at least 1.5 mg%

(-) - a-Bisabolol:

at least 10.0 mg%

40

Mixing devices, for example so-called bowl mixing machines, percolators and other suitable extraction apparatuses, can be used for the extraction, for example. The temperature during the extraction is, for example, 10 to 50 ° C. Cooling is not necessary.

Straight or branched aliphatic, mono- or polyhydric alcohols with 1 to 6 carbon atoms such as, for example, methanol, ethanol, propanol (2), butanol, glycerol, isopropylidene glycerol and the like, and mixtures of these solvents with water are particularly suitable as solvents .

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

Fresh chamomile flowers or frozen chamomile flowers (if fresh flowers have been frozen) can also be used for the production of extracts, in particular alcoholic extracts.

An essential oil obtained from the drug contains at least 3.5% chamazulen, preferably at least 5% chamazulen and at least 10% (-) - a-bisabolol, preferably at least 15%) (-) - a-bisabolol and less than 10% other bisaboloids.

Such an essential oil is generally prepared by adding the drug to water, for example in the presence of ascorbic acid (for example as a salt, in particular as a sodium salt) at a pH between 4 and 6, preferably 5 to 5.5 Boiling heated. The pH is adjusted, for example, using an acid such as hydrochloric acid. For example, 10 to 50 parts by weight of water and optionally 0.1 to 1 part by weight of ascorbic acid are used per 1 part by weight of the dried material.

It is generally heated for 2 to 8 hours.

The aqueous distillate obtained is shaken several times with a lower aliphatic, liquid hydrocarbon (for example petroleum ether (for example b.p. 35-60 ° C.), pentane, xylene, decalin), the organic phase is dried (for example using sodium sulfate) and the organic Solvent removed in a gentle manner (for example by distilling off in a rotary evaporator or by distillation at 40-70 ° C, preferably at 50-60 ° C). In the case of higher-boiling solvents, this distillation is carried out under vacuum.

The ingredients are determined as already stated.

If the flowers of the chamomile according to the invention are harvested at a stage of vegetation where 30-100% of the tubular flowers of a flower head are open and the flowers are dried at an air temperature of up to 70 ° C., a drug obtained in this way contains, for example, at least 30 mg% chamazulen, at least 100 mg% (-) - a-bisabolole and less than 50 mg% of other bisaboloids and an essential oil made from this drug by distillation in the presence of water at least 3.5% chamazulen, at least 10% (-) - a- Bisabolol and less than 10 mg% of other bisaboloids, and an alcoholic chamomile extract made by extraction with lower alcohols at least 1.5 mg% chamazulen, at least 5.0 mg% (-) - a-bisabolol and less than 10 mg% of others Bisaboloids.

Are the flowers of the chamomile according to the invention harvested in the vegetation stage where 30-70% of the tubular flowers of a flower head are open and the flowers

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Dried at an air temperature of not higher than 50 ° C, such a drug contains, for example, at least

100 mg% chamazulen, at least 200 mg% (-) - a-bisabo-

101 and less than 50 mg% of other bisaboloids, an essential oil, if any, made therefrom at least 3.5%) chamazulen, at least 10% (-) - a-bisabolol and less than 10%) of other bisaboloids, and one from this drug produced alcoholic extract at least

5.0 mg% chamazulen, at least 10.0 mg% (-) - a-bisabo-lol and less than 10.0 mg% of other bisaboloids.

If the flowers of the chamomile according to the invention are harvested in the vegetation stage where 30-70% of the tubular flowers of a flower head are open and the flowers are dried at an air temperature between 50-70 ° C., the drug thus obtained contains, for example, at least 50 mg% chamazulen, at least 150 mg% (-) - a-bisabolole and less than 50 mg% of other bisaboloids, an essential oil possibly made therefrom at least 3.5%) chamazulen, at least 10% (-) - a-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from such a drug at least 2.5 mg% o chamazulen, at least 7.5 mg% (-) - a-bisabolol and less than 10.0 mg% of other bisaboloids.

If the flowers are harvested at the vegetation stage where 70-100% of the tubular flowers of a flower head are open and the flowers are dried at an air temperature of not higher than 50 ° C, the drug thus obtained contains, for example, at least 40 mg% chamazulen, at least 120 mg% (-) - a-bisabolol and less than 50 mg% of other bisaboloids, an essential oil possibly made from them at least 3.5% chamazulen, at least 10%) (-) - a-bisabolol and less than 10% of others Bisaboloids and an alcoholic extract made from this drug at least 2.0 mg% chamazulen, at least 6.0 mg% (-) - a-bisabolol and less than 10.0 mg% of other bisaboloids.

If the flowers of the chamomile according to the invention are harvested in the vegetation stage where 70-100% of the tubular flowers of a flower head are open and the flowers are dried at an air temperature between 50-70 ° C, the drug thus obtained contains, for example, at least 30 mg% chamazulen, at least 100 mg% (-) - a-bisabolole and less than 50 mg% o of other bisaboloids, an essential oil possibly made from it at least 3.5% chamazulen, at least 10% (-) - a-bisabolol and less than 10 % of other bisaboloids and an alcoholic extract made from this drug at least 1.5 mg% chamazulen, at least 10 mg% (-) - a-bisabolol and less than 10.0 mg% of other bisaboloids.

example 1

Individual plant variability tests of the diploid, low-bisabolol-containing but not bisabolol-free camomiles, which are described in Franz, Ch., J. Hölzl and A. Vömel: Acta Hor-ticulturae 73, 109-114 (1978), found that maximum up to 20% of all individuals in the essential oil have a chamazulene content of approximately 20% by weight and / or a high (-) - a-bisabolol content of 50% by weight, the content of the other bisaboloids (in particular (-) - a-bisabolone oxide) is very low. These individuals were selected and tetraploidized as follows:

Seeds of the chamomile plants selected in this way were applied to a filter paper saturated with 0.05% aqueous colchicine solution and left to swell at room temperature (20 ° C.) for 6 hours. They were then removed from the filter paper, rinsed several times with water and placed in seed

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ssten (greenhouse) sown: soil: peat-sand mixture 1: 1, temperature: 18 to 20 ° C, relative humidity: approx. 60%, day length with artificial lighting: 14 hours.

The germinating plants were observed until flowering, the success of polyploidization was determined by comparative measurement of the pollen and seed size and by chromosome counting of the plants (Fi progeny = first progeny grown from seeds of the tetra-ploid-confirmed colchicinated plants).

The tetraploidization can also be carried out in the following way:

5 to 7 days old, well-developed chamomile seedlings germinated on water-soaked filter paper were placed in a 0.05% colchicine solution with the cotyledons at room temperature (20 ° C.) for 4 to 6 hours. The sensitive germ roots were spared; In order to prevent damage to them from drying, the surrounding atmosphere must have almost 100% relative humidity. After the treatment, the seedlings were rinsed several times with water and pricked into plant boxes. The further treatment was carried out as for the seeds.

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

Chromosome counting takes place at root tips: 1 to 2 cm long fresh root ends are collected from the young plants or cuttings grown in the greenhouse, 5 hours in 0.002 molar hydroxyquinoline solution and then placed in IN HCl for 15 minutes. For the examination, approximately 1 mm of the root tips are stained with 2% orcein acetic acid and examined microscopically in oil immersion. In the cells in mitosis, the 4-fold chromosome set of the somatic cells can be determined (4n = 36).

Those plants in which the pollen diameter is approximately 50% larger than that of the diploid starting material (approximately 30 instead of approximately 20 µm) and in which the chromosome set of the somatic cells was doubled to 36 (for the diploid starting material the corresponding number is 18) are tetraploid . These have been selected. Approximately 0.1 to 0.5%) of the seeds or seedlings were tetraploidized using the above method and developed flowerable, intact plants.

Step 1:

From the progeny of the selected tetraploid chamomile plants as described above, those individuals were selected who reached or exceeded a minimum chamomule content of 100 mg% and (-) - a-bisabolol of 200 mg% and whose content of other bisaboloids (especially bisabolol oxides) is less than 50 mg%. All values refer to flower heads that have been dried at approx. 40 ° C and which were harvested at the stage when approx. 30-70% of all tubular flowers of a head are open.

Step 2:

All of the blossoming flower heads were removed from the plants obtained after step 1, then the plants came into a greenhouse and bloomed together under isolated conditions. The plants were placed in 11 cm pots, filled with garden soil, at 18 to 24 ° C day and 12 to 14 ° C night temperature. The day length was at least 14 hours and was achieved in the winter half-year by additional exposure (200 watts / m2). The water supply was carried out as needed.

From the totality of the selected individuals, those heads that had faded and were shortly before decay were continuously harvested over a period of 4 weeks for seed production. Drying took place in a well-ventilated hall at an air temperature between 20-30 CC; the seeds were then sieved using a slotted sieve (5 x 0.4 mm) and cleaned using a riser.

The seed obtained after step 2 is the propagation seed of the chamomile according to the method.

Flowers of plants from this propagation material (sowing September / October, harvest early June of the following year), which are picked at the time when 30 - 70% of the tubular flowers are open, and which are then immediately dried in a drying cabinet at 40 ° C for 72 hours were, based on the weight of the dried flowers, at least 100 mg% chamazulen, at least 200 mg% (-) - a-bisabolol and at most 50 mg% other bisaboloids.

Obtaining the drug:

The chamomile obtained according to this example is sown in the field in the usual way. As soon as the plants have developed and the flower heads are in the vegetation stage, where about 50% of the tubular flowers are open, these flower heads are harvested with a chamomile picking machine, the comb spacing of the picking machine being set so that only the flower heads, the tubular flowers, close 50% are open to be stripped. The crop is transported as quickly as possible to a shady place and spread there in a thin layer until further processing. The flower heads are then freed from the stems in a sieving system and dried to constant weight. The weight loss is about 80% i. Drying takes place in the shade in a well-ventilated place on trays in a layer thickness of about 10 cm.

The drying process ends after about 2-3 days. The chamomile drug is sifted to remove stem parts and pollen and then pressed into bales. analysis

Essential oil: 910 mg%

Chamazulen: 117 mg%

(-) - cc-bisabolol: 252 mg%

If drying is carried out, for example, in a stationary belt drying plant using artificially heated air at a temperature between 50 and 70 ° C, the drying will be finished after about 4-5 hours. The drug is sifted to remove stem parts and pollen and then pressed into bales. The analytical values of such a drug are usually somewhat lower than the above values.

Example 2

Individual plant variability tests of the diploid, low-bisabolol-containing but not bisabolol-free camomiles, which are described in Franz, Ch., J. Hölzl and A. Vömel: Acta Hor-ticulturae 73, 109-114 (1978), found that up to a maximum of 20% of all individuals in the essential oil have a chamazule content of about 20% by weight and / or a high (-) - a-bisabolol content of 50% by weight, with the content of the other bisaboloids (in particular (-) - a -Bisabolon-oxide) is very low. These individuals were selected and exactly as indicated in Example 3 is tetraploidized and the tetraploid individuals were selected.

About 0.1 to 0.5% of the seeds or seedlings were tetraploidized and developed flowerable, intact plants.

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Step 1 :

From the progeny of the selected tetraploid chamomile plants (as described above), those individuals were selected which:

A) bloom at about the same time,

B) have a uniform, basic branching and a narrow flowering zone of approximately 10 cm, preferably 5 cm,

C) have large flower heads with an outside diameter of approximately 30 mm, preferably 25-35 mm,

D) achieve or exceed a minimum content for chamazulen of 150 mg% and bisabolol of 300 mg% and their content of other bisaboloids (especially bisabolol oxides) is well below 50 mg%. (All values refer to flower heads that were dried at 40; C and were 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 (mother clone plants) were first cut back to about 15 cm shoot length, under 8 to 10 hours of day length and 12 to 14 ° C brought to new shoots (short side shoots). The short shoots were cut and placed in a peat-sand mixture. At around 100% relative humidity, 15 ° C air temperature and a day length of 14 hours, the rooting of the cuttings took 7 to 14 days.

Instead of the specified conventional cloning (cutting propagation), the in vitro propagation of tissue parts of the plant capable of division can also be used (so-called meristem propagation). To establish a

Chamomile culture is suitable for different parts of the plant, preferably the shoot tips or the armpit buds. .

After rinsing the plants with H2O2, shoot tips of the leaf axillary buds are removed under aseptic conditions in the "laminar flow" (high-performance suspended matter filter with low-turbulence displacement flow) and transferred to test tubes that are mixed with a nutrient medium, e.g. according to Murashige and Skoog (Physiol. Plant. 15,473-497, 1962). The reagent glasses are placed in a climate room with a length of 12-18, preferably 16 hours (achieved by fluorescent fluorescent tubes), a light intensity of 500-10,000 lux, preferably 1000-3000 lux and a temperature of 15-30 CC, preferably 22- 27 C.

15 As soon as the explants show good growth, they are placed on a nutrient medium mentioned above, but with a higher cytokinin concentration * (for example 30 mg / 1 6-isopentenyladenine) and little or no auxin (0-0.3 mg / 1 indole acetic acid) transferred. As a result, the axes stretch and adventitious organs and more axillary buds are formed. These can be removed and tightened in the manner mentioned above.

The explants intended for plant propagation in large numbers (the 3rd passage = 3rd generation of the 25th generation) are transferred after growth and formation of the leaves on the first-mentioned nutrient medium to a nutrient medium which is 10 mg / 1 indole acetic acid or 3-indol butyric acid or 0.1-0.3 mg / 1 a-naphthylacetic acid. The plantlets take root and can be planted in pots filled with sterilized garden soil (steamed for 12 hours at 120 CC) after 30 to about 4 weeks and cultivated further in the greenhouse (under conditions as is usual for conventional cuttings).

Culture medium according to Marashige & Skoog:

mg / 1 mg / 1

NH4NO3 400 indole acetic acid 2.0

Ca (No3) 2 • 4 H2O 144 furfuryladenine 0.1

KNO3 '80 thiamine 0.1

KH2PO4 12.5 nicotinic acid 0.5

MgSÛ4 • 7 HiO 72 pyridoxine 0.5

KCl 65 glycine 2.0

NaFe-EDTA 25 myo-inositol 100

H3BO3 1.6 casein hydrolyses. 1000

MnS04 • 4 H20 6.5 Saccarose 2%

ZnS04 • 7 HiO 2.7 cleaned

KJ 0.75 agar powder 1%

* Cytokinins are phytohormones that promote cell division.

Step 2:

The plants obtained after step 1 flowered together under isolated conditions in the greenhouse. The plants stood in 11 cm pots, filled with garden soil, at 18 to 24 ° C day and 12 to 14 C night temperature. The day length was at least 14 hours and was achieved in the winter half-year by additional exposure (200 watts / m2). The water supply was carried out as needed.

From the totality of the selected individuals, those heads that had faded and were shortly before decay were continuously harvested over a period of 4 weeks for seed production. Drying took place in a well-ventilated hall at an air temperature between 20 - 30 C; the seeds were then sieved using a slotted sieve (5 x 0.4 mm) and cleaned using a riser.

Step 3:

A sample was taken from the seed obtained after step 2 and approximately 2000 offspring were drawn from it (ecological conditions as in step 2) and selected from step 1 according to the same criteria A) to D). The individuals selected in this way were then operated according to step 2.

60 Step 4:

A part of the seed according to step 3 was sown at two different locations in autumn.

Location I)

450 m NN, 48.5 "N / 11.5; O,

65 750 mm annual precipitation amount,

humid-temperate climate,

January —10 to 0 "C,

July +10 to +20 "C,

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12

NN = north Nonnalnull = sea level ■ N = northern latitude (degrees)

~ 0 = east longitude (degrees)

Location II)

200 m NN, 42e N / 1; O,

400 mm annual precipitation amount,

Mediterranean climate,

January 0 to +10 "C,

July +20 to + 30aC.

Sowing was carried out at both locations in late September / early October.

The field trial stocks obtained in this way were checked and assessed (rated) with regard to homogeneous growth, flower size and harvest date, and random samples of the flowers were also examined for the active substance content. From the field stock, those individuals were selected which correspond to the parameters mentioned in step 1. From these seeds are obtained according to step 2, last sentence.

Step 5:

With the seed according to step 4, steps 3 and 4 were repeated in the order and manner given.

Step 6:

Approximately 1500 individuals were grown from the seed obtained after step 5 (ecological conditions as in step 2) and selected according to the same principle as stated in step 1. 34 individuals were selected from the plants selected in this way and cloned according to step 1. 10 plants from each clone were planted in a random distribution at a distance of 40 x 30 cm outdoors (location I, see step 4) at an isolated location. The soil was loess loam, pH 7.0; planting took place in early June, the first harvest of the seeds in mid-July, then the plants were cut back, bloomed again and delivered a second seed harvest in mid to late August.

This material was harvested according to step 2.

The seed obtained after step 6 is the propagation material of the chamomile according to the process.

Flowers of plants from this propagation material (sowing September / October, harvest beginning of June of the following year), which are picked at the time when 30 - 70% of the tubular flowers are open, and which were then immediately dried in a drying cabinet at 40 3C for 72 hours , based on the weight of the dried flowers (dry substance), for example at least: 150 mg% chamazulen, 300 mg% (-) - a-bisabolol and at most 50 mg% other bisaboloids.

Further exemplary information on the camomile plants obtained according to the example:

1.Growth

Stems: upright, little branched;

2. Foliage

Leaf: pinnate, 2 to 3 fold;

Strength: medium;

Leaflet, color medium green;

Leaflet (middle of stem); Pinnation: medium to strongly pinnate;

3. Inflorescence

Flower heads (flower heads):

30 mm outer diameter,

15 mm inner diameter;

Single basket weight (dry): approx. 45 mg;

Flower sprout, length (mm): approx. 700, but depending on the place of cultivation (climate), sowing date, soil, fertilization, plant treatment, weather;

Beginning of flowering (day from January 1st):

about 160th day (sowing September, location Freising Federal Republic of Germany, otherwise depending on the factors mentioned above).

Flowering: mid-June (see above);

Inflorescences without peduncle, essential oil content (% of dry matter): approx. 1.0%; Azulene content in essential oil: at least 15%;

Disintegration of the dried inflorescences, flower drug: low if harvested before opening the last tubular flowers;

Pollen diameter: approx. 30 [im;

Seed length: approx. 1.25 mm;

Chromosome number of somatic cells: 4 n = 36;

4. Fruit

Thousand grain mass (TCM) of the seeds: 0.06 to 0.13 g;

5. Germination (KF)

about 75%;

6. Purity

94-95%;

7. Other features

Drying ratio fresh: dry (flowering) = 5.5 to 6: 1, characteristic aromatic smell of the drug, fine aromatic, typical taste of the tea infusion.

In addition, the following properties can be present: Uniform growth height (balance) with a narrow flowering zone, therefore particularly suitable for mechanical harvesting, large flower heads, medium-high yield; basically branched (3 to 5-fold) form.

Obtaining the drug:

The chamomile obtained according to this example is sown in the field in the usual way. As soon as the plants have developed and the flower heads are in the vegetation stage, where about 50% of the tubular flowers are open, these flower heads are harvested with a chamomile picking machine, the comb spacing of the picking machine being set so that only the flower heads and their tubular flowers are closed 50% are open to be stripped. The crop is transported as quickly as possible to a shady place and spread there in a thin layer until further processing. The flower heads are then freed from the stems in a sieving system and dried to constant weight. The weight loss is about 80%). Drying takes place in the shade in a well-ventilated place on trays in a layer thickness of about 10 cm.

The drying process ends after about 2-3 days. The chamomile drug is sifted to remove stem parts and pollen and then pressed into bales.

analysis

Essential oil: 1020 mg%

Chamazulen: 173 mg%

(-) -cc-Bisabolol: 418 mg%.

If drying takes place, for example, in a stationary belt drying system using artificially heated air at a temperature between 50 and 70 "C, the drying will be finished after about 4 - 5 hours. To remove stem parts and flower grass, the drug is sieved and then pressed into bales.

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The analytical values of such a drug are usually somewhat lower than the above values.

Example 3

Production of an extract from chamomile drug. The chamomile flowers for the drug used are harvested according to Example 1 at a time when 30-70% of the tubular flowers are open and dried at an air temperature of not higher than 50 ° C.

400 g of the chamomile drug thus obtained with a content of 105 mg% chamazulen and 212 mg% (-) - a-bisabolol are mixed with 2100 g aqueous ethanol (40% by weight ethanol) in a bowl mixer at a speed of the mixer of 30 revolutions per extracted for 3 hours. The drug substance is then squeezed out and the extract is filtered.

The active substance content in the extract is determined in a known manner:

Chamazulen: 3.7 mg%

(-) - a-Bisabolol: 10.2 mg%

Example 4

Production of an extract from fresh chamomile 758 g of fresh chamomile flowers of a camomile, which according to Example 2 are harvested at a time when 30-70% of the tubular flowers are open (water content 74%) are combined with 510 g of ethanol (84% by weight) Dump mixer extracted at a mixer speed of 65 revolutions per minute for 30 minutes. The drug substance is then squeezed out and the extract is filtered.

The active substance content in the extract is determined in a known manner:

Chamazulen: 11.7 mg%

(-) - a-Bisabolol: 16.3 mg%

Example 5

Production of an essential chamomile oil 200 g of dried chamomile flowers obtained according to Example 2 (drying was carried out at 50 ° C. with the exclusion of sunlight) are mixed with 3.61 water and 2 g of sodium ascorbate in a 5 liter round bottom flask; the mixture is adjusted to a pH of 5.0 with 1N HCl. After adding boiling stones, the mixture is heated to boiling. Approx. 1.21 distillate are collected within approx. 3 hours.

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

The content of chamazulen and (-) - a-bisabolol is then determined in the essential oil obtained. Yield: 1.44 g essential oil

Chamazulen: 3.6% i. oil

(-) - a-Bisabolol: 10.2% i. oil

Appendix A Extraction of the essential oil The starting material is a drug from the chamomile according to the invention. For the manufacture of the drug, only those flower heads are used in which 30 to 70%, in particular 40 to 60%, of the tubular flowers are open. Drying takes place in a drying cabinet at 40 ° C for 72 hours.

The essential oil of the chamomile flowers is obtained by steam distillation of the drug for two hours as described below:

2.0 g of non-comminuted drugs are mixed with 250 ml of deionized water in a round-bottomed flask and subjected to a two-hour reflux distillation in a Clevenger apparatus (water vapor distillation reflux apparatus for the quantitative determination of small amounts of essential oils). 1 ml of pentane per 5 analyzes is used as a template. The return speed is 40 + 4 drops / minute. After the distillation has ended, the essential oil dissolved in pentane is drained as free of water as possible into test tubes and any remaining essential oil adhering to the apparatus is rinsed with pentane. To remove any water residues, a spatula tip of dried Na2S04 is added to the solution and the solution is then sucked off through a glass filter of porosity D 3 or D 4 in crimped vials. After the pentane has evaporated at 40 QC in a water bath and dried i5 in a desiccator, the amount of oil is determined gravimetrically.

The chamazulen and the bisabolol are then determined in the oil thus obtained (approx. 20 mg).

Spectrophotometric determination of chamazulen 20 measuring solution: The entire essential oil (approx. 20 mg) obtained from 2 g of drug (obtained as described above) is dissolved in 25 ml of n-hexane or cyclohexane. 25 Measuring device: filter photometer (for example

Eppendorf).

Wavelength: 578 nm

Cuvette: 1 cm

Specific extinction of chamazules

(1 g / 100 ml; 1 cm): 20.8

Compensation liquid: n-hexane or cyclohexane Found content 35 of chamazulene in mg / 100 g: 120 E57s

If no filter photometer is available for the measurement, the determination can also be carried out with a spectrophotometer:

40 measuring device: spectrophotometer (for example PM QU / or PM Q III «ZEISS»)

Wavelength: 605 nm

Cuvette: 1 cm

45 Specific absorbance of chamazulen (1 g / 100 ml; 1 cm): 24.5

Compensation liquid: n-hexane or cyclohexane as found Chamazulen content in mg / 100 g: 102E605

The bisabolol is then determined in the measurement solution.

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Gas chromatographic determination of the bisabolol and the other bisaboloids Gas chromatograph: Hewlett Packard model 5750,

Erba Fractovap 2350 or similar device

Detector: flame ionization detector

Carrier gas: helium

Pillar: 1 / s inch; 200 cm; stole

Column filling: 3% nitrile silicone rubber «XE 60»

65 silanized on diatomaceous earth

"Chromosorb WAW HP" 125 to 150 (in the carrier material

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Temperature: Detector: Injection block: Column: Temperature programming: Sample solution:

Comparative solution:

320 ° C 220 ° C 85-220 ° C

4 ° / minute

The measurement solution for chamazulen is used. Approximately 150 mg of standard bisabol are dissolved in 25 ml of cyclohexane

Of sample solution and comparison solution each 5 (0.1 The evaluation is carried out by comparison of the peak areas

10 x sample weight (comparison) [mg]

x area (sample)

Area (comparison)

The other bisaboloids can also be determined by gas chromatography, for example under the following recording conditions:

Injection quantity:

Evaluation:

Bisabolol content in mg per 100 g drug:

Equipment:

Columns:

Filling:

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Carrier gas:

Temperature program: injector / detector temperature: i5 detector: injection quantity:

Packard, model 7721, series 800 or Erba Fracto-vap series 2350 glass columns, 3 m / 2 mm in diameter; 2 m / 2 mm in diameter

3% methylphenyl silicone rubber "OV 1" on kieselguhr silanized "Gaschrom Q" 125 to 150 (in the carrier material 30 ml / minute N?

80 to 180 ° C, 2.5 (3) "C / minute

200 ° C

Flame ionization detector approx. 2 | xl of the approx. 1:50 diluted essential oil The evaluation takes place partly without, partly with an internal standard. As an internal standard, 20-lauric acid or hexadecane are suitable for low-chamazulen or chamazulen-free oils. In the case of oils with a chamazule content of more than 5%, this should be preferred as the internal standard, with the content being determined photometrically (at 578 nm).

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Claims (15)

671 674 PATENT CLAIMS 1. Process for the production of plants or propagation material of the bisabolol-rich, tetraploid chamomile of the crop type real chamomile (Chamomilla recutita (L.) Rauschert, synonymous with Matricaria chamomilla L., Astera-ceae), whose flowers dried at 40 ° C, based on the Have dry matter, at least 100 mg% chamazulen, at least 200 mg% (-) - a-bisabolol and less than 50 mg% of other bisaboloids, characterized in that a diploid chamomile by means of chemicals at temperatures between 0 and 35 ° C, by means of Gamma rays, X-rays or UV rays at temperatures between 0 and 35 ° C, by means of high temperatures from 33 to 50 ° C, by means of low temperatures from 0 to 5 ° C, tetraploidized by means of the decapitation callus method or an anther culture with subsequent tetraploidi -sation subjects and selected from the tetraploid camomiles obtained those plants in which (-) - a-bisabolol is the main component of the ethereal Oil and their flowers dried at 40 ° C at least 100 mg% chamazulen, at least 200 mg% (-) - a-bisabo- Contain 101 and less than 50 mg% of other bisaboloids, or first select from a diploid chamomile population those plants in which (-) - a-bisabolol is the main component of the essential oil and whose flowers dried at 40 ° C at least 100 mg % Contain chamazulen and 50-100 mg% (-) - a-bisabolol and the plants thus obtained are tetraploidized and selected as indicated above, with the proviso that that the diploid starting chamomile is different from the chamomile variety «Degumill». 2nd d) drawing offspring from the seed obtained according to c), selecting these offspring according to a), cloning the plants selected in this way and obtaining seed from the plants obtained by the cloning. 2. The method according to claim 1, characterized in that a diploid chamomile, in which (-) - a-bisabolol is the main component of the essential oil, by means of chemicals at temperatures between 0 and 35 ° C, by means of gamma rays, X-rays or UV Radiation at temperatures between 0 and 35 ° C, by means of high temperatures from 33 to 50 ° C, by means of a low temperato from 0 to 5 ° C, by means of the decapitation-callus method tetraploidized or subjected to an anther culture with subsequent tetraploidization and from the tetra obtained -ploid chamomile, in which (-) - a-bisabolol is the main component of the essential oil, selects those plants whose flowers dried at 40 ° C at least 100 mg% chamazulen, at least 200 mg% (-) - a-bisabo- Contain 101 and less than 50 mg% of other bisaboloids and subject such plants to further selection and propagation steps, with the proviso that the diploid chamomile is different from the chamomile variety «Degumill». 3rd 671 674 essential oil at least 3.5% chamazulen, at least 10% (-) - a-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from them at least 2.0 mg% chamazulen, at least 6.0 mg% (- ) -a-bisabolol and less than 10.0 mg% of other bisaboloids. 3. The method according to claim 2, characterized in that the selection and propagation steps consist in the following: a) Selection of at least 10 individuals of the tetraploid plants obtained according to the active ingredient content of at least 100 mg% chamazulen, at least 200 mg% bisabolol and less than 50 mg% other bisaboloids based on the dry matter, simultaneous flowering, uniform basic branching and a flower head size of 20 to 40 mm, cloning of the plants selected in this way and extraction of seeds from the plants obtained by the cloning; b) drawing offspring from the seed obtained according to a), subsequent selection according to a) and obtaining seed from the plants selected in this way; c) repeating the measures according to b) three to five times; 4. Chamomile or chamomile propagation material obtained by the process according to one of claims 1 to 3. 5. A method for producing a chamomile drug, characterized in that a chamomile according to claim 4 io is used. 6. The method of claim 5, wherein fresh, frozen or dried flowers of the chamomile are used. 7. The method according to claim 5, wherein the flowers of the chamomile are used, characterized in that the 15 flowers are harvested in a vegetation stage, where 30 to 100% of the tubular flowers of a flower head are open and the flowers are dried at an air temperature up to 70 ° C, whereby a drug obtained in this way at least 30 mg% chamazulen, at least 100 mg% (- ) -a-Bisabo-20 loi and less than 50 mg% of other bisaboloids, and if necessary an ethereal oil is obtained from the drug thus obtained by distillation in the presence of water, which contains at least 3.5% chamazulen, at least bisl0% (- ) - <x-bisabolol and contains less than 10% of the remaining 25 bisaboloids or produces an alcoholic chamomile extract by extraction with lower alcohols, which contains at least 1.5 mg% chamazulen, at least 5.0 mg% (-) - a-bisabolol and contains less than 10 mg% of other bisaboloids. 30th 8. The method according to claim 5, wherein the flowers of the chamomile are used, characterized in that the flowers are harvested in the vegetation stage, where 30 to 70% of the tubular flowers of a flower head are open and the flowers at an air temperature of not higher than 35 be dried than 50 ° C and this drug at least 100 mg% chamazulen, at least 200 mg% (-) - cc-bisabo- Contains 101 and less than 50 mg% of other bisaboloids and any essential oil made from them at least 3.5% chamazulen, at least 10% (-) - a-bis- 40 abolol and less than 10% of other bisaboloids and an alcoholic extract made therefrom at least 5.0 mg% chamazulen, at least 10.0 mg% (-) - a-bisabolide and less than 10.0 mg% of other bisaboloids contains. 45 9. The method according to claim 5, wherein the flowers of the chamomile are used, characterized in that the flowers are harvested at the stage of vegetation where 30-70% of the tubular flowers of a flower head are open and the flowers at an air temperature between about 50-70 ° C are dried and the drug thus obtained contains at least 50 mg% chamazulen, at least 150 mg% (-) - a-bisabolol and less than 50 mg% of other bisaboloids, and any essential oil made therefrom at least 3.5% chamazulen, at least 55 10% (-) - a-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from them at least 2.5 mg% chamazulen, at least 7.5 mg% (-) - a-bisabolol and less than 10, Contains 0 mg% of other bisaboloids. 60 10. The method according to claim 5, wherein the flowers of the chamomile are used, characterized in that the flowers are harvested in the vegetation stage, where 70-100% of the tubular flowers of a flower head are open and the flowers at an air temperature of not higher than 65 dried at 50 ° C and the drug thus obtained contains at least 40 mg% chamazulen, at least 120 mg% (-) - a-bisabolol and less than 50 mg% of other bisaboloids and, if appropriate, a 11. The method according to claim 5, wherein flowers of chamomile are used, characterized in that the flowers are harvested in the vegetation stage, where 70-100% of the tubular flowers of a flower head are open and the flowers at an air temperature between 50-70 "C and the drug thus obtained contains at least 30 mg% chamazulen, at least 100 mg% (-) - a-bisabolol and less than 50 mg% of other bisaboloids and any essential oil made from them at least 3.5 % Chamazulen, at least 10% (-) - a-bisabolol and less than 10% of other bisaboloids and an alcoholic extract made from them at least 1.5 mg% chamazulen, at least 10 mg% (-) - a-bisabolol and less than 10 , 0 mg% of other bisaboloids. 12. Chamomile drug obtained by the method according to any one of claims 5-11. 13. Chamomile drug according to claim 12, the at least 100 mg% chamazulen, at least 200 mg% (-) - a-bisabo- Contains 101 and less than 50 mg% of other bisaboloids. 14. Chamomile drug according to claim 12 in the form of an essential oil, produced by the method according to claim 7, characterized in that it contains at least 3.5% chamazulene and at least 10% (-) - a-bisabolol and less than 10% of other bisaboloids contains. 15. Chamomile drug according to claim 12 in the form of alcoholic chamomile extracts, produced by the method according to claim 6, characterized in that it contains at least 1.5 mg% chamazulen and at least 5.0 mg% (-) - a-Bisabolol and less than 10 mg% of other bisaboloids.