DE950027C - Process for the preparation of injectable extracts of horse chestnut - Google Patents

Description

Process for the production of injectable extracts of the horse chestnut object the invention is a process for the production of extracts from horse chestnuts, which are injectable and for which the hemolytic effect of the water-alcoholic in these Extracts contain saponins through the formation of an addition compound saponin-cholesterol is largely canceled without the content of the therapeutically effective extract substances to change.

In the case of plant extracts which have the character of saponin, it may be in certain cases In some cases it can be therapeutically beneficial to bring the substances directly into the bloodstream. Such an application is only possible if the aforementioned hemolytic Effect of the saponins is eliminated. It stands to reason for such detoxification reactions To use cholesterols.

The production of saponin-cholesterol addition compounds is known for a long time. The numerous publications that have appeared so far However, it can be seen that in order to arrive at useful products, the Formation of these addition compounds from pure saponins of various origins ran out of.

According to a known method, for. B. the saponin in O, I- bis I% solution in water or physiological saline solution with 0.1 to 10% shaken essential cholesterol solution, the ether evaporated and the residue filtered off from the deposited precipitate.

It is also known to use an aqueous or saline o, 10 / o Saponin solution alternating with a 0.1% solution of cholesterol in acetone Volume ratio to move, warm up and a few hours at one temperature of about 500 to hold. The acetone is then evaporated at 600 and the precipitate filtered off.

Finally, it is already known to use a 10% solution for the Saponins in 90 per cent alcohol in a hot state with an alcoholic cholesterol solution to move. An addition compound fails. You also have the saponin longer in aqueous solution with cholesterol, which is almost insoluble in water Time boiled on the reflux condenser.

As has been shown, the methods mentioned cannot to satisfy. Above all, they are uneconomical and depend on certain conditions, namely the use of pure saponins. In addition, it remains questionable whether in this way and way sufficiently eliminates the harmful effects of saponins on erythrocytes can be.

These deficiencies cannot be eliminated even if one of an alcoholic-aqueous horse chestnut extract goes out and this after the previously known procedures. If you process the one that has been freed from alcohol aqueous extract of the horse chestnut using the ether method, a slimy one is produced Precipitation, which is with the help of the known Filtrationsmetboden and procedures can not be separated from the solution.

Even centrifugation at 40,000 revolutions per minute causes it only a partial separation.

If, on the other hand, an extract containing 30% alcohol is processed, as is usually obtained from the extraction of the horse chestnut with aqueous alcohol is, the precipitate is obtained in a form that is easier to filter, it finds however, there is no or only a very slight decrease in hemolysis.

You cannot eliminate these disadvantages even if you use the Concentration of saponins, cholesterol and the volume ratio of the two liquid phases changed within wide limits. However, it is desirable to have a quick and safe elimination of the hemolytic effectiveness of the horse chestnut extracts below Avoidance of high temperatures for a longer period of time at the same time Achieving easy filterability of the precipitate.

It has now been found that the difficulties identified can be overcome can by using an aqueous-alcoholic extract solution obtained from horse chestnuts Brings cholesterol to action and the conditions of action in relation to temperature, Duration of exposure and the amount of cholesterol used adjusts the alcohol concentration of the extract so that at a lower alcohol concentration milder conditions, but more energetic or with higher alcohol concentrations stricter exposure conditions in terms of exposure time and temperature selected will.

The cholesterol is generally in a 1 to 1,50% range essential solution, but can also, especially with higher alcohol concentrations of the extract and at higher induction temperatures, without the addition of further solvents come into use.

In a preferred embodiment of the new method an aqueous rig-allholic horse chestnut extract solution which z. B. 7 to 120/0, preferably 10% ethanol contains the same volume of 1.5% essential cholesterol solution added, shaken and then the ether evaporates, whereupon after filtering off and washing out the resulting precipitate with distilled water, the Extralit solution by evaporating the alcohol under reduced pressure and diluting with aqua pro inj. is worked up on ready-to-use injection solution.

However, one can also proceed by using an essential cholesterol solution on the alcoholic horse chestnut extract, which originally contained around 300/0 ethanol Leave to act for about 24 hours at normal temperature and after distilling off of the ether and the separation of the precipitate, the filtrate is repeated with ethereal Cholesterol solution treated in the same way.

The inventive method has the advantage that the necessary Removal of the alcohol from the extract and the ether cholesterol treatment in interlock in an optimal way. The substances obtained using the new process are particularly suitable for the treatment of certain circulatory disorders. they are can also be administered intravenously. After all, the new process also works economically, in particular, the consumption of cholesterol is relatively low.

Should horse chestnut extract solutions with higher contents of ethanol, e.g. 70 to 20 ° / o, are processed, then the action of the cholesterol must take place at higher temperatures in order to obtain extracts which are not hemolventically effective. In this case, the procedure is expediently so that the extract solution, which is on a Alcohol content of, for example, 85% has been brought directly to about 2 to ° / o cholesterol and several hours at average temperatures of about 50 to 600 heated under the reflux condenser.

After cooling, the precipitate formed is filtered off and the solution worked up in the manner already described to give a ready-to-use injection solution.

The following is the implementation of the method according to the invention explained in more detail using a few examples.

Example 1 An extract from horse chestnuts in 300 / above alcoholic Solution is first the alcohol by vacuum distillation up to a content of about 10 per cent withdrawn. Thereafter, the extract becomes 1 volume 1% more ethereal Cholesterol solution shaken and then the ether evaporated.

The resulting precipitate is centrifuged and filtered off and with aqua pro inj. rewashed. Then you steam under the remaining alcohol slightly reduced pressure, thinned the residue up to one Content of 3 O / o dry substance with aqua pro inj., Filtered sterile and ampouled in a known way.

Example 2 A 30% alcoholic horse chestnut extract is mixed with 2.5 volumes of a 10% essential cholesterol solution were stirred. You let him then stand covered overnight at room temperature.

The following day the ether is distilled off and the residue in the still filtered off from the precipitate formed. The filtrate will again mixed with 2.5 volumes of 10% essential cholesterol solution, and how treated further above. Finally, the same procedure is repeated a third time. The solution is then evaporated until the alcohol content is below 2%.

After this, as in the lead example I, it is diluted and filtered free of germs the solution is ready to be filled.

Example 3 The horse chestnut extract is made by adding alcohol brought to an alcohol content of about 85% and the mixture 2 to 40/0 cholesterol added. The solution is refluxed on a water bath for 5 hours 50 to 600 heated and filtered off from the precipitate after cooling. The filtrate is freed from alcohol in vacuo, filtered sterile and bottled.

Attempts have also been made to extract horse chestnuts by treating the Mash the horse chestnut seeds with alcohol, separate and discard the extract, renewed extraction of the residue with 960% alcohol and reaction of this To precipitate a saponin product from an extract with saturated alcoholic cholesterol solution, which was expected to have pharmacodynamic effects.

In this known method, the first one containing the active ingredient is used Extract is not processed further as according to the present invention, but discarded.

Claims (4)

PATENT CLAIMS: I. Process for the preparation of injectable extracts the horse chestnut with elimination of its hemolytic effect by means of cholesterol, characterized in that a horse chestnut extract solution containing alcohol Cholesterol, preferably dissolved in an organic solvent such as ether, is brought to action, the conditions of action in terms of temperature, Duration and amount of cholesterol used depending on the alcohol concentration of the extract can be chosen so that a lower alcohol concentration is milder Conditions and a higher alcohol concentration are more energetic conditions correspond to exposure time and temperature, whereupon the solution after filtering off and washing out the resulting precipitate under reduced pressure from alcohol and optionally other non-aqueous solvents and freed by addition is brought to the desired final content by aqua plro injections. 2. The method according to claim I, characterized in that one between 7 and 12 / o, preferably 10 / o / o alcohol-containing extract an essential cholesterol solution added, after evaporation of the ether, the resulting precipitate is filtered off and is washed with distilled water and the filtrate in vacuo from the remaining Ethanol is freed. 3. The method according to claim I, characterized in that one is on an extract containing about 30% alcohol; an essential cholesterol solution leaves to act for about 24 hours and after evaporation of the ether and separation of the resulting precipitate the filtrate repeated with cholesterol solution in the same Treated wisely. 4. The method according to claim I, characterized in that one is on an extract solution, after adjusting the ethanol content to about 85%, cholesterol lets act for several hours at about 50 to 600. Publications considered: Bulletin des Sciences Pharmacologiques, XLVII, No. 11/12, 5.310.