DE2407910C3 - 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 low 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 K) elementary units develop tanning effects; about that in addition, they are no longer soluble.

Some tannin supplements are also known for their therapeutic properties, especially as astringent 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 are known under the name »Galbules«, contain tannins, Jie has long been in human history · rapie used to treat venous disease will. According to the state of the art, these tannins are obtained as total extracts of the fruits of the Cupressus sempervirens usually with 30-40% by volume igerri or SOvoh & igem ethanol or with aqueous methanol, isopropanol, acetone, Me- * ethyl ethyl ketone, etc., with suitable water components 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 from the fruits of Cupressus sempervirens by obtaining a certain tannin fraction compared to the known total tannin extracts 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 heavily condensed

! 5 tannins, on the other hand, by leaching out the weakly condensed tannins (with about 90% alcohol by volume) into preparations formed by the strongly condensed tannins with eir. si leads to a very significant physiological effect on the venous system, which has so far been masked by the simultaneous presence of the weakly condensed tannins endowed with a certain corresponding inhibitory effect.

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 Content of strongly condensed tannins increases regularly when the young fruit is of the minimum size grows to a weight of 5 g, which takes about 3 months (from March to June in the southeast from France). Then the salary remains from the 4th to

8th month constant, while the fruit increases from 5 to 10 to 12 g (from July to October in the southeast from France). After that, the content of condensed tannins decreases rapidly and becomes around the 10th up to 11th month practically zero (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. The applicant has also found in the valley 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.

Based on these findings, the method of the present invention for obtaining an active vein Extract from the fruits of Cupressus sempervirens by single or multiple extraction with an aqueous solvent is accordingly characterized in that the between the 4, and 8th month after flowering or on the tree Remaining fruits of Cupressus harvested between 16 and 20 months after flowering sempervirens extracted that the total extract obtained to separate the contained therein weakly condensed tannins, if necessary, after evaporation

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

The fruits of Cupressus sempervirens are preferably used either immediately after harvesting or after a longer storage period, which can reach several months, whereby storage should take place at a temperature in the region of +5 ⁰ C under conditions which are suitable prevent both mold formation and dehydration 2U, as z. B. it was found that the fruits collected in the 6th month when stored in a cold room of + 5 ° 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 tinnines 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 take a reasonable length of time in the region of 1.5 to 3 stur the stirred and then the insolubles separated by filtration as a filter cake, which is filled with fresh, about 90% by volume (90 ° G L.) Ä '.lanol washed and finally preferably in vacuum and at a 50 ° C temperature not exceeding. · Itur is dried to achieve about 90vol. % (90 ° G.L.) Alcohol-insoluble, water-soluble, highly purified, strongly condensed tannins.

The vein-active (especially contracting) Tanninex- to which can be obtained according to the invention trakt is more effective than 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.

An explanatory example of the extraction follows and the pharmacological test of the inven = appropriate tannin extracts,

example
A) Extraction of the tannins ^ ₅

1000 kg were used between the 4th and 8th, Möriät harvested after flowering, appropriately harvested Washed fruits or, fruit cones of the cypress, The fruits became pieces of a few millimeters crushed, which immediately in a container with 2000 l boiling under reflux, about 50vol.% igem (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 stirred for 2 hours at room temperature. After that it became the insoluble Separated portion on the filter, the cake with fresh, about 90vol.% (90 ° G.L.) alcohol was washed. The filter cake sucked off or spun off was in a granulator zerteik and for vacuum drying at one Temperature, which should not exceed 50 ° C, distributed over plates. The dry granules were then crushed to the desired grain size. In this way, 25 to 35 kg of condensed tannins became obtain.

B) Pharmacological examination

On the basis of pharmacological studies, in which vein motility tests were carried out, it could be shown that those from fruits Little condensed tannins extracted from Cupressus sempervirens, d. H. those that are roughly 90% alcohol by volume (90 ° G.L.) are soluble, practically no effect on the veins of mammals exercise while the highly condensed tannins isolated according to the invention and both are insoluble in about 90% alcohol (90 ° G.L.) as well as soluble in water, an important physiological one Have potency that is considerably 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 overpressure or effective pressure) and Recovery of the perfusate via the previously isolated inferior vena cava was carried out with the flow through a photoelektn'scheii drop counter measured, Known amounts of vein-constricting products could be injected into the aorta via a branch That led to a reduction in the perfusion rate, after the exit or departure of the the throughput should be 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 decrease in the flow rate in the ratio 1: 5. The experiment was repeated on 10 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 rate 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 ¹ Z 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 less condensed tannins, which also has 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 erfindungsge.-wet condensed cypress tannins have been extensively clinical for both the treatment of hemorrhoidal symptoms and tried by 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 changes.

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. The dose is maintained for 3 days in which Time the acute crisis subsides.

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

D, is cypress tannin gives one at these doses rapid effect, with a pain-relieving component found in all examinations. When using this tannin, the administration of pain relievers can be dispensed with In addition, the tannin extract is one of the rare anti-hemorrhoidal products which can be administered orally: its effect does not need to be supplemented by local treatment and thus means a considerable gain in terms of convenience of supply.

In the vein area, the cypress tannins according to the invention Administered in all chronic infiltration conditions, the main indication is the syndrome heavier legs. The cypress tannins according to the invention are also useful in the case of sequelae 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 län- ■ = Consider longer treatment durations over a month and re-administrations. as Dosage is 1 to 2 capsules per day, i.e. H. 300 to 600 mg of tannin is advisable.

With the so-called heavy legs, excellent results are obtained, 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 used:

a) for facial tonic with a low alcohol content, of which aftershave is a lower example, b) as "sun filters" or sunscreen preparations to protect the skin during prolonged exposure to the sun, especially in the mountains.
The astringent properties of the tannins and their antiseptic properties are used in facial tonics. Their concentration is 1 to 2% in dilute ethanol, and its concentration is 15 to 30% by volume. % lie ku, nn.
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 commonly used fragrances 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 the absorption capacity from the first half hour of irradiation. The absorption capacity remains 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. You k'öniien in the form of lightly alcoholic solutions (30 ° G.L.) applied or in all forms of emulsified creams of the type

oil-in-water, i.e. of the "cold-cream" type will.

The cypress tannins are included with all emulsifiers used in the preparation of "eold-cream"

24 07 9iÖ

Exception of polyoxyethylene compatible.

An example of an anti-allergic »coldcream« could have the following composition:

- whale rat 16 g

- white wax 8g

- almond oil

- Zypfessefitannin

- Sodium borate

- Essence as you wish

- 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 the Cupressus sempe.rvirens 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 with about 90vol. % alcohol treated and those in it 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.