DE2407910B2 - Process for obtaining a vein-active extract from the fruits of Cupressus sempervirens - Google Patents

Description

The invention relates to a method for obtaining a vein-active extract from the Fruits of Cupressus sempervirens by single or multiple extraction with an aqueous solvent as well as a vein-active tannin extract and cosmetic or pharmaceutical preparations.

Tannins are known to be widespread in the plant kingdom and can be obtained from tree bark (e.g. from oak and mangroves), woods (oak, chestnut, quebracho etc.), roots (especially oak), Leaves (sumac) or fruits (gonakia, dividivi, myrobalans, etc.) can be extracted. Well known is their ability to keep skins from rotting. Those made from fruits of Cupressus sempervirens (Cypress) extractable tannic mass is made by a mixture of more or less formed condensed or agglomerated molecules, of which the tannins are of low molecular weight (Molecules with less than 5 elementary units or "motifs") for tanning hides are unsuitable, while those with 5 to 10 elementary units develop tanning effects; about that in addition, they are no longer soluble.

Some tannin supplements are also known for therapeutic properties, particularly as astringent ones Means endowed with an anti-diarrhea and hemorrhage counteraction. It is also known that the fruits of Cupressus sempervirens, which are known as round cones and in France Known as "Galbules", they contain tannins that have long been used in human therapy used to treat venous disease. These tannins are after State of the art as total extracts of the fruits of Cupressus sempervirens usually with 30 to 40% by volume or 50% by volume ethanol or with aqueous methanol, isopropanol, acetone, methyl ethyl ketone etc. with suitable proportions of water in the cold or at only slightly elevated temperatures obtain. However, these known extracts have only a moderate therapeutic effectiveness and could therefore not acquire any particular significance. Surprisingly, however, it has now been found that the therapeutic effectiveness of tannin preparations made from the fruits of Cupressus sempervirens by obtaining a certain tannin fraction in comparison to the known total tannin extract

K) th can be increased extraordinarily, namely that the separation of the by Total extraction of the fruit of Cupressus sempervirens obtained tannic mass in weakly condensed Tannins on the one hand and strongly condensed tannins on the other hand due to the dissolution of the weakly condensed tannins (with about 90vol.% alcohol) to by the strongly condensed Tannin-formed preparations with a very significant physiological effect on the venous system leads that so far by the simultaneous presence of with a certain corresponding Inhibitory effect of gifted weakly condensed tannins was masked.

On the other hand, the applicant has found that the content of the fruits of Cupressus sempervirens strongly condensed tannins is subject to considerable fluctuations and depending on the season in which the fruits are harvested can even go to zero. So the applicant was able to determine that the

jo content of strongly condensed tannins increases regularly when the young fruit grows from the minimum size to a weight of 5 g, what lasts about 3 months (from March to June in the south-east of France). Then the salary remains from the 4th to

J5 8th month constant, while the fruit went from 5 to 10 to 12 g increases (from July to October in the south-east of France). After that, the Gehali takes on condensed Tannins decrease rapidly and become practically zero around the 10th to 11th month (January to February in the southeast of France).

The extracts of cypress fruit thus have a maximum therapeutic value when in the Summer are made, while those made with extracts made with fruits harvested in winter, if at all, have very little therapeutic value. The content of cypress fruits condensed tannins seems to the temperature curve and even more likely to the rhythm to follow the renewal and refreshment of the juices. Indeed, the applicant has found, in addition, that the fruits that remain on the tree beyond the 12th month are removed when they are taken up again or loaded with condensed tannins when the juices rise again in spring, but all in one less than during the initial cycle.

The method according to the invention based on these findings for obtaining a vein-active Extract from the fruits of Cupressus sempervirens by single or multiple extraction with an aqueous solvent is accordingly characterized in that the between the 4th and 8th month after flowering or those that remained on the tree and between the 16th and 20th month After flowering harvested fruits of Cupressus sempervirens extracted that one the total extract obtained to separate the slightly condensed tannins contained therein, possibly after evaporation

Treated to dryness with about 90% alcohol by volume (with 90 Gay-Lussac degrees) and those in it insoluble highly condensed tannins as an effective fraction wins.

The fruits of Cupressus sempervirens are preferably used either immediately after harvest or after a longer storage time, which can reach several months, the storage should take place at a temperature in the region of +5 ⁰ C under conditions that are suitable for both mold formation as well as to prevent dehydration, as z. B. it was found that the fruits collected in the 6th month when stored in a cold room of +5 ⁰ C under the conditions mentioned retain their content of condensed tannins for a long time. If, on the other hand, the same fruits are left in the air at ambient temperature, they open, lose or loosen their seeds and dry out, after which no more strongly condensed tannins are found in them.

In the practical implementation of the method, one starts in particular with crushed cypress fruits which are extracted with boiling about 50% by volume (50 ° G.L.) ethanol. The received Extract is preferably made under reduced pressure and at a temperature not exceeding 50 ° C concentrated, freed from insoluble resins and dispersed in about 85% by volume (85 ° G.L.) ethanol. the Dispersion will be a reasonable time on the order of 1.5 to 3 hours at room temperature stirred and then the insolubles separated by filtration as a filter cake, which is filled with fresh, Washed about 90vol.% (90 ° G.L.) ethanol and finally preferably in a vacuum and at a A temperature not exceeding 50 ° C is dried to achieve approximately 90% by volume (90 ° G.L.) Alcohol-insoluble, water-soluble, highly purified, strongly condensed tannins.

The vein-active (in particular contracting) tannin extract obtainable according to the invention has an increased effectiveness compared to known total extracts and can therefore be used less Amount to be used. It is easily tolerated in daily doses of over 1 g. He can be used with good success in phlebitis and acute hemorrhoidal complaints will.

In the cosmetic field, its astringent and certain antiseptic effects in particular can be used for facial toner, whereby its good tolerance in the quantities to be used with usual perfumes and antiseptics and its slightly amber color of additional Are interested. In addition, the extract has a very high photosensitivity and is therefore suitable for »sun filters« or sun protection preparations.

The invention therefore includes cosmetic and pharmaceuticals which can be used in human and veterinary medicine Preparations.

The following is an illustrative example of the production and pharmacological testing of the substances according to the invention Tannin extracts.

example
A) Extraction of the tannins

1000 kg were used between the 4th and Appropriately washed fruits or cones of cypresses harvested 8th month after flowering.

The fruits were chopped into pieces of a few millimeters, which were immediately placed in a container with 2000 1 refluxing, about 50 vol.% (50 ° G.L.) ethyl alcohol to inactivate the enzymes were given. The mass was left for 0.5 hours after the extractor was fully charged kept simmering. Then the heating was turned off and the 2000 l alcohol was drawn off and replaced by fresh 2000 1 50% alcohol, which was brought to the boil and held for 0.5 hours became. After cooling, the extract was drawn off and combined with the first extract.

The 4000 l alcoholic extract were under reduced pressure of 20 to 40 torr at a evaporated temperature not exceeding 50 ° C so far that about 400 l remained. The so concentrated extract obtained was freed from insoluble resins and carefully filtered, and then in one Vacuum dryer or, better, dried by atomization. In this way they were 70 to 85 kg obtained compound tannins in powder form.

These composite or complex tannins were 5 times the volume (based on the Weight) about 85% by volume (85 ° G.L.) ethyl alcohol dispersed and the dispersion for 2 hours at Stirred at room temperature. Thereafter, the insoluble fraction was separated on the filter, leaving the cake with fresh, about 90% by volume (90 ° G.L.) alcohol was washed. The filter cake sucked off or spun off was in a granulator divided and for vacuum drying at a temperature that should not exceed 50 ° C, distributed on plates. The dry granules were then crushed to the desired grain size. on in this way 25 to 35 kg of condensed tannins were obtained.

B) Pharmacological examination

Based on pharmacological studies in which venous motility tests were performed, it was possible to prove that those extracted from the fruits of Cupressus sempervirens condensed little Tannins, d. H. those that are soluble in about 90% by volume (90 ° G.L.) alcohol are practical have no effect on the veins of mammals, while the highly condensed tannins, which are isolated according to the invention and are both insoluble in about 90% by volume (90 ° G.L.) alcohol as well as being soluble in water, have a significant physiological activity, which is very considerable is higher than that of the total tannins.

Hind legs of the frog (Rana esculenta) were used for the experiments and the procedure was as follows:

In the case of a perfusion with Ringer's liquid via a cannula connection in the section of the preceding isolated lower aorta under constant pressure (about 15 cm water column pressure or differential pressure) and Recovery of the perfusate via the previously isolated inferior vena cava was carried out with the flow through measured with a photoelectric dropper. Known to the aorta could be branched out Quantities of vein-constricting products are injected which lead to a reduction in the perfusion flow rate led. After the product injected into the perfusate has emerged or has passed away, the throughput should return to normal. The goal was,

by means of a few tests (carried out as quickly as possible so as not to tire the preparation) to determine the dose which leads to a temporary reduction in the flow rate in the ratio 1: 5. The experiment was ^{repeated on 11} J animals. According to this technique, it was found that an average of 40 μg of strongly condensed tannins or 200 to 300 μg of total tannins (depending on their composition) are required to _{reduce the flow to V 5.}

With about 90vol. % (90 ° GL) alcohol-soluble, weakly condensed tannins, it is not possible to _{reduce the flow to V 5} , since injections of 1000 μg (1 mg) of weakly condensed tannins achieve a maximum reduction to V ₂ . Higher doses lead to irreversible changes in the preparation and are therefore no longer physiologically sensible.

These results show the high potency of the heavily condensed tannins as opposed to the very low effectiveness of the little condensed tannins, which also have a pronounced inhibitory effect unfold if left mixed with highly condensed tannins (as in the total tannin extract the case is). Hence the need to remove the weakly condensed Tannins, if you want to achieve an improved therapeutic effect.

C) Clinical results (submitted later)

The condensed cypress tannins of the present invention have been widely used clinically for both treatment tested for hemorrhoidal complaints as well as venous diseases.

In these experiments, the pure tannins in jelly capsules (gelules) with 300 mg of tannin were used. Such capsules are the most convenient for administration and storage. To the exclusion of Light and moisture keep the tannins for several years without any noticeable change.

In the treatment of acute hemorrhoidal crises, the tannin extracts give remarkable results Results. A suitable dosage is 1200 mg of tannin per day, divided into four individual doses of 300 mg each. This dose is maintained for 3 days, during which time the acute crisis subsides.

As a preventive treatment, 300 to 600 mg per day are administered, which is the case for patients with tendency to hemorrhoidal crises can be repeated periodically.

The cypress tannin gives a quick effect at these doses, with one in all investigations pain reliever component was noted. When using this tannin can therefore be on the administration dispense with pain relievers. In addition, the tannin extract belongs to the rare antihemorrhoidal products that can be administered orally: its effects does not have to be supplemented by a local treatment and is therefore a considerable benefit regarding convenience of care.

In the vein area, the cypress tannins according to the invention are used in all chronic infiltration states administered. The main indication is heavy legs syndrome. The cypress tannins according to the invention but are also associated with sequelae of phlebitis and traumatic edema useful.

A major concern in the vein area is the treatment of chronic dysfunction that are rarely completely reversible. One must therefore longer -> longer treatment periods over a month and consider re-administrations. The dosage is 1 to 2 capsules per day, i. H. 300 up to 600 mg of tannin appropriate.

With the so-called heavy legs you get excellent results, both objectively the size and weight of the affected extremities as well as a subjective feeling of relief and the elimination of the tingling leg.

_{| 5} D) Cosmetic applications (submitted later)

The cypress-derived condensed tannins according to the invention can be of two different types Types of cosmetic preparations applied:

a) for face tonic with a low alcohol content, of which aftershave is a particular example; b) as "sun filters" or sunscreen preparations to protect the skin during prolonged exposure to the sun, especially in the mountains.
2) The astringent properties of the tannins and their antiseptic properties are used in facial toners. Their concentration is 1 to 2% in dilute ethanol, the concentration of which can be 15 to 30% by volume.
jo The amber color of the tannins is desirable and makes the use of artificial coloring in such facial toners superfluous. The cypress tannins are compatible with the fragrances normally used and with antiseptic agents such as boric acid.

A facial toner can, for example, have the following composition:

- water 61.2%

- Ethyl alcohol 28% - Boric acid 2 %

- menthol 0.1%

- perfume 1 %

- cypress tannin 1.2%

- Glycerin 6.5% For cosmetic applications as a »sun filter« one can take advantage of the very high photosensitivity of cypress tannins.

The reactions that develop during exposure to light cause a considerable increase in

%) decrease in the absorption capacity from the first half hour of irradiation. The absorption capacity is retained for several hours.

At the same time, the absorption spectrum broadens. At the beginning, the cypress tannins absorb at 275 nm. After exposure to the sun, a continuous absorption plateau is observed between 270 and 340 nm. The cypress tannins filter very effectively UV rays and in the visible near Area.

As a »sun filter«, the cypress tannins come in levels of 1 to 5%, depending on what you want Degree of protection for use. They can be used in the form of slightly alcoholic solutions (30 ° G.L.) .) which in all forms of emulsified creams of the type

Oil-in-water, d. H. brought in by the "cold-cream" type will.

The cypress tannins are included with all emulsifiers used in the preparation of cold cream

Except for polyoxyethylenes compatible. - almond oil

An example of an anti-allergenic cold cypress tannin

cream «could have the following composition: - Sodium borate

- Whale Rat 16 g - essence as desired

- white wax 8 g · "> - distilled water for

Claims (3)

Patent claims: 1. Process for obtaining a vein-active extract from the fruits of Cupressus sempervirens by single or multiple extraction with an aqueous solvent, characterized in that that between the 4th and 8th month after flowering or those left on the tree and between the 16th and 20th The fruits of Cupressus sempervirens harvested one month after flowering were extracted so that the obtained Total extract to separate the slightly condensed tannins it contains, if necessary after evaporation to dryness treated with about 90vol.% alcohol and the therein insoluble highly condensed tannins as an effective fraction wins. 2. Vein-active tannin extract from the fruits of Cupressus sempervirens, available from Claim 1. 3. Cosmetic or pharmaceutical preparations, characterized by a content of tannin extract according to claim 2.