CZ287992B6 - Process for preparing chamomile essential oil with total content of natural cis- and trans-spiroethers of at least 1 percent by weight - Google Patents

Abstract

Camomile oil with a content of natural cis- and trans spiro ethers of, in total, at least 1 wt.%, is new. The camomile oil can be prepd. by steam distn. or distn. with water of fresh camomile or extn. residues from camomile extn. Water distn. is pref. carried out at pH 4-8, opt. in the presence of reductants. The extracts pref. contain cis and trans spiro ethers in a total amt. of at least 1.0 mg/100g extract, esp. at least 0.5mg cis and 0.3mg trans spiro ether per 100g extract. The resulting camomile oil pref. contains at least 1 wt.% cis and 0.5 wt.% trans spiro ether, and can be added to any physiologically acceptable solvent to give more camomile extract.

Description

A process for producing chamomile oil having a total content of natural cis- and trans-spiroethers together of at least 1 wt.

Technical field

The invention relates to a process for the production of chamomile essential oil with a total content of natural cis- and transspiroethers together of at least 1% by weight.

BACKGROUND OF THE INVENTION

Chamomile (Chamomilla recutita Rauschert (syn. Matricaria chamomilla L.)) is used as such or in the form of various preparations. The effect of chamomile is attributed to hydrophilic active substances, such as flavones and polysaccharides, and to lipophilic active substances, which are contained in camomile oil.

Of the camomile lipophilic active ingredients, in addition to (-) -. Alpha.-bisabiol and chamazulene, polyines such as cis- and trans-ene-in-dicycloether (= spiroether) are also important for assessing the quality of camomile and camomile extract. Camomile spiroethers have anti-inflammatory and spasmolytic properties. However, these spiroethers are readily decomposed, especially when heated.

Camomile oil can be obtained either by distillation or extraction of the camomile drug, i.e., dried camomile flower baskets.

Although distillation allows almost one hundred percent recovery of the other essential components, therapeutically important thermolabile spiroethers are largely disrupted in this process. The essential oil obtained by distillation therefore no longer contains a set of active substances typical of camomile. However, even by extraction, camomile oil is not fully recovered. For example, when producing liquid extracts with 45% ethanol, only about half of the drug contained bisabolol and chamazulen containing essential oils with delicate spiroethers pass into the extract.

SUMMARY OF THE INVENTION

It has now been unexpectedly found that chamomile essential oils are obtained by distillation of chamomile extract residues (drug extraction residues or fresh chamomile extracts) or fresh chamomile flowers, which have a high polyin content, in particular thermolabile cis- or trans, through thermal treatment. -en-in-bicycloether.

It is therefore an object of the present invention to provide a camomile oil having a total content of natural cis- and trans-spiroethers together of at least 1% by weight, comprising subjecting fresh camomile or camomile extract residues to steam distillation or water distillation.

In a preferred embodiment of the process according to the invention, the camomile oil obtained contains a content of natural cis-spiroethers of at least 1% by weight. and a natural trans-spiroether content of at least 0.5 wt.

Preferably, the water distillation in the process of the invention is carried out at a pH in the range of 4 to 8, optionally with the addition of reducing agents.

In a further preferred embodiment of the method according to the invention, the camomile oil produced comprises at least 2.0 wt. natural cis- and trans-spiroethers, wherein the content of natural cis-spiroethers is at least 1.5% by weight. and a natural trans-spiroether content of at least 0.5 wt.

The structure of cis-spiroether (cis-en-in-bicycloether) can be represented by this structural formula

-1 CZ 287992 B6

The trans-spiroether (trans-en-in-bicycloether) has the structure

The process according to the invention makes it possible for the first time to produce a camomile essential oil having a specific content of a set of active ingredients of camomile. This camomile oil is suitable, for example, as an additive to water-alcoholic camomile extracts, which thus obtain a high content of essential oil with lipophilic as well as camomile active ingredients, while retaining a typical set of camomile active ingredients.

In addition, the process according to the invention makes it possible to economically utilize residues from the extraction of camomile, whereby the essential oil still contained in the residues from the extraction of camomile drug or fresh camomile is recovered unchanged with its active ingredients. Thus, in addition to a better yield of active substances, considerable savings in the raw materials for the production of the extract are achieved.

In the distillation of the residue from the extraction of fresh chamomile flowers or unprocessed chamomile flowers, not only the need for expensive drying equipment is eliminated, but also the considerable operating costs of conventional pre-treatment of the raw material to be distilled by drying are eliminated. The production costs of the extract preparations can thus be substantially reduced.

The addition of chamomile oil produced by the process according to the invention, which contains a large number of spiroethers, also produces extracts containing a typical set of active substances in a mixture with chamomile oils obtained by the usual distillation process in the production of chamomile extract preparations.

In steam distillation according to the method of the invention, hot steam 25 is supplied to the distillation vessel either at atmospheric pressure or under an overpressure of up to 0.4 to 0.5 MPa. The hot steam may be under a positive pressure of, for example, 0 to 0.1, preferably 0 to 0.05 MPa. Its temperature can be, for example, between 100 and 140 ° C (at most 145 ° C), preferably between 100 and 130 ° C, most preferably between 105 and 115 ° C.

The distillation takes 2 to 10 hours, preferably 2 to 4 hours. In the case of steam distillation, no additives are added to the distilled raw material. The distillation may be continuous or intermittent.

Water distillation in the process of the invention is carried out by heating a distillation vessel filled with water (temperature, for example, 100 ° C). One part by weight of the raw material to be distilled is mixed with at least one part by weight of water, preferably 10 to 100 parts by weight, preferably 10 to 60 parts by weight of water, which may contain conventional additives such as reducing agents (for example ascorbic acid or ascorbate). sodium) or inorganic acids (e.g. hydrochloric acid, sulfuric acid) and alkali metal hydroxides (e.g. dilute sodium hydroxide) to adjust the pH. The distillation may be carried out at pH values between 4 and 8. Preferably, however, the pH adjustment is not carried out so that the distillation takes place in a neutral

-2GB 287992 B6. The distillation is terminated after 1 to 4 hours, preferably after 2 to 3 hours. The amount of reducing agents added is, for example, 0.1 to 1 wt. part per 1 wt. part of vegetable raw material.

The raw material to be distilled may be crushed before distillation. The moisture content of the raw material is, for example, an average of 60% (water-alcohol) in the extract from the camomile extraction, and an average of 80% (water) in the fresh camomile. The distillation may be carried out in conventional mobile or stationary distillation vessels.

The distillate condensed by cooling is collected, for example, in a device allowing the separation of camomile oil from water on the basis of a different specific weight (for example in a Florentine bottle, but also in other conventional separating vessels, possibly with a centrifuge device).

After separation of the aqueous phase, the top phase of the camomile oil can be used without further purification, for example, to produce camomile extract preparations. Separation of the phases can be facilitated, for example, by the addition of a salt such as sodium chloride (salting out).

For distillation with water, the distillation apparatus may optionally be flushed with a low boiling lipophilic solvent, for example a liquid saturated aliphatic hydrocarbon of 5 to 7 carbon atoms (for example n-pentane, petroleum ether), one or more times (two or three times). The purpose of the flushing is to remove the last residual oil from the still. For flushing, for example, 1 to 2 parts by weight of hydrocarbons are used per 1 part by weight of the dry residue of the extraction residue used. After removal of the hydrocarbon as described below, the residue is added to the camomile oil of the aqueous distillate.

When the hydrocarbon is added to the aqueous distillate, the active substances of the distillate are transferred to the hydrocarbon. The hydrocarbon phase is then separated from the aqueous phase in a known manner, for example by adding sodium chloride (salting out), followed by repeated shaking (for example twice) of the aqueous phase with a hydrocarbon. After drying the hydrocarbon phase, the camomile oil is obtained by removing the hydrocarbon, conveniently at a temperature in the range of 40 to 60 ° C. The last hydrocarbon residues can be removed, for example, by a stream of warm air (40 to 60 ° C).

Fresh chamomile flowers here are chamomile flowers that distill or freeze within 2 hours of being picked.

The process according to the invention is generally applicable and is therefore suitable for all camomiles which contain spiroethers. In particular, the following camomiles are used: diploid variety camomile Degumill (protected in the former GDR under the Variety Protection Act, German patent 24 02 802, Italian patent 1 035 096), tetraploid camomile Manzana (German published application 34 23 207), tetraploid varieties chamomile according to German published publication 35 42 756.

Other possible camomile diploid varieties: "Chamomile of Argentine origin" (LZ Padula, RVD Rondina and JD Coussio, Quantitative determination of essential oil. Total azulene and chamazulene content in German camomile, Matricaria chamomilla, grown in Argentina, Planta med. 275 to 280 (1976) as well as all camomiles which contain (-) - abisabolol in clearly measurable concentrations in the essential oil, generally over 5%. Also suitable are diploid chamomiles described in this literature: Schilcher H., "Recent findings in assessing the quality of chamomile essential oil or chamomile flowers", Planta med. 23, 132-144 (1973), Motl O., M. Folklova, V. Lukes and M. Jasicova, "For Analysis by Gas Chromatography and Chemical Types of Chamomile Oil", Arch. Pharm. 310, 210-215 (1977), Ch. Franz, J. Holzl and A. Vomel "Preliminary morphological and chemical characterization of some populations and varietiesMatricariachamomillaL", ActaHort. 73, 109-114 (1978).

Also suitable are, for example, the following tetraploid camomile varieties: Bodegold (GDR), Pohořelický (ČSSR), Zloty Lan (Poland), BK-2 (Hungary), which are described in this literature: M. Chládek, V. Kosová, K. Gross: Pharmazie 13, 712-718 (1958), W. Czabajska, Diss. Poznan (1963), W. Poethke and P. Bulin, Pharm. Znalle, 108, 813-823 (1965), L. Sarkany, Herb. Hungar. 4 (1), 125-169 (1965).

-3GB 287992 B6

Suitable residues of camomile extraction which can be used in the process according to the invention are those which are obtained conventionally in the usual extraction of a camomile drug or fresh camomile with alcohols or an alcohol-water mixture. These are, for example, straight or branched aliphatic alcohols having 1 to 6 carbon atoms as well as Solketal (2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane), for example methanol, ethanol, 1-propanol, 2-propanol, butanol and the like. Mixtures of these solvents and mixtures thereof with water may also be used. In these aqueous mixtures, the water content is, for example, up to 65, preferably 20 to 60, most preferably 30 to 55 volume percent.

Extraction residues can be subjected to the distillation according to the invention immediately, even in the wet state. However, they can also be dried first (at 40 to 60 ° C for 2 to 5 hours) and after 10 storage if necessary (at 15 to 25 ° C and 40 to 50% relative humidity) and processed by the process according to the invention .

The camomile oil obtained by the process of the invention comprises at least 1, preferably at least 1.5, most preferably 2 weight percent of polyins (sum of all polyins), being natural polyins. For example, the content of all polyins is 2 to 20, preferably 4 to 18, in particular 10 to 15, by weight 15 percent. The content of cis-spiroethers is, for example, at least 1, preferably 2 to 18, in particular 5 to 15 weight percent. The content of trans-spiroethers is, for example, at least 0.5, preferably 0.5 to 15, in particular 1 to 10, percent by weight. The chamazulene content is, for example, 0.9 to 8% by weight, preferably 3 to 6% by weight. The content of α-bisabolol is, for example, 5 to 30, preferably 22 to 32, percent by weight. The content of bisabolol oxide A is, for example, 1 to 10, preferably 20 to 2, by weight. The content of bisabolol oxide B is, for example, 0.8 to 15, preferably 2 to 4% by weight.

The camomile oil obtained by the process according to the invention is added with stirring, either in pure form or as a solution in a physiologically acceptable solvent (e.g. ethanol), to the aqueous alcoholic camomile extracts obtained by a known process. The aqueous alcoholic extracts are, for example, extracts obtained using ethanol or isopropanol. The alcohol content of the extract should not exceed 20% by weight. The extract should generally contain 20 to 55, preferably 20 to 50, in particular 20 to 40, percent by weight alcohol. The addition of camomile oil obtained by the process according to the invention to such extracts should be calculated so that the resulting product contains 100 to 250 mg, preferably 180 to 200 mg of essential oil per 100 g of 30 alcoholic or aqueous-alcoholic extract. The content of bisabolol, for example using camomile-rich chamomile, is then 20 to 100 mg, preferably 40 to 80 mg per 100 g of extract. The extract then contains, for example, 1.5 mg cis- and trans-spiroether per 100 g.

Camomile extracts or camomile extract preparations which are prepared by adding camomile oil produced by the process of the invention contain, for example, at least 35 1.0 mg, preferably 1 to 10 mg and especially 2 to 5 mg of polyins per 100 g. The cis-spiroether content is at least

0.5 mg, preferably 0.7 to 4.0 mg and in particular 1.0 to 3.0 mg per 100 g. The content of the trans-spiroether is at least 0.3, preferably 0.7 to 3.0, in particular 0, The content of chamazulene is for example 3 to 25 mg, preferably 3 to 20 mg, in particular 3 to 18 mg per 100 g. The content of α-bisabolol is for example 30 to 100 mg, preferably 30 to 80 mg The content of bisabololoxide A is, for example, 5 to 30 mg, preferably 5 to 25 mg, in particular 5 to 20 mg per 100 g.

The content of bisabololoxide B is, for example, 3 to 20 mg, preferably 3 to 18 mg, in particular 3 to 15 mg per 100 g.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

In a 1000 ml round-bottomed flask, mix 41 g of chamomile ⁺ residue (corresponding to 10 g of dry matter) with 500 ml of water; The pH of the mixture was adjusted to 6.5 by the addition of dilute sodium hydroxide solution, after which the mixture was distilled for about 3 hours. A 1000 ml shaking funnel is used as a collection vessel. After obtaining 400 ml of distillate, distillation was continued for a further 2 minutes without cooling. The distillation head and condenser are then rinsed with 80 ml of pentane.

Pentane is added to the distillate and, after addition of 65 g of sodium chloride, the mixture is shaken and then added

Repeat shaking twice more, each time with 80 ml of pentane. The combined organic phases were dried over 8 g of anhydrous sodium sulfate and filtered. The receiver and filter are washed twice with 10 ml of pentane each, then the pentane phase is carefully evaporated to a volume of 5 ml (fragrance bath at 50 ° C, rotary evaporator). The remainder of the pentane was stripped off with a stream of warm air (50-60 ° C, hair dryer).

A camomile oil of the following composition is obtained:

chamazulen bisabolol A bisabolol B (-) - α-bisabolol cis-spiroether trans-spiroether 3.6% 2.7% 4.1% 20.5% 10.2% 1.7%.

⁺⁾ This is a chamomile residue from a chamomile extraction performed with a mixture of ethanol and water (47: 53 v / v). The chamomile drug used was a bisabolol-rich drug, which was made from chamomile of the Degumill variety according to German patent 24 02 802.

Comparative example (known procedure)

Using the procedure of Example 1, 10 g of dried chamomile flowers are distilled (the drug is identical to the chamomile drug prior to the extraction used in Example 1).

The essential oil obtained by distillation has the following composition: chamazulene (-) - α-bisabolol bisabololoxide A bisabololoxide B cis-spiroether trans-spiroether

7.6%

24.4%

1,6%

1,7%

0.2% not detected.

Example 2

12.5%

22.1%

4.7%

3.4%

11.8%

7.3%.

Into a two-necked 1000 ml flask was added 37.8 g of fresh camomile of Degumill variety rich in bisabolol (corresponding to 10 g of the drug, ie, dried camomile flowers). After inserting the distillation head with the ball cooler, water vapor is supplied to the flask through the side neck of the steam generator. The distillation was stopped after 4 hours.

The top phase of the distilled oil was separated using a Florentine bottle. The essential oil composition as determined by analysis is as follows: chamazulene (-) - α-bisabolol bisabololoxide A bisabololoxide B cis-spiroether trans-spiroether

Comparative example (known procedure)

Using the procedure of Example 2, 10 g of dried chamomile flowers are distilled (the drug is identical to the gently dried chamomile used in Example 2).

-5r

The camomile oil, separated from the top phase of the distillate, has the following composition:

chamazulen 9.6% (-) - α-bisabolol 21.2% bisabololoxide A 3.0% bisabololoxide B 3.9% bis-spiroether 1.2% trans-spiroether 0.5%.

PATENT CLAIMS

Claims (5)

PATENT CLAIMS A process for producing camomile essential oil with a total content of natural cis- and trans-spiroethers together of at least 1% by weight, characterized in that fresh camomile or extract residues from camomile extraction are subjected to either steam distillation or water distillation. Method according to claim 1, characterized in that the camomile oil produced has a natural cis-spiroether content of at least 1% by weight. and a content of natural transspiroethers of at least 0.5 wt. Process according to claim 1 or 2, characterized in that the distillation with water is carried out at a pH of from 4 to 8, optionally with the addition of reducing agents. Method according to claims 1 to 3, characterized in that the camomile oil produced has a total content of natural cis- and trans-spiroethers together of at least 2.0% by weight. A process according to claims 1 to 3, characterized in that the camomile oil produced has a total content of natural cis-spiroethers of at least 1.5% by weight. and a natural trans-spiroether content of at least 0.5 wt.