DE2118916A1 - Water-soluble acid saponin mixts prodn - by extraction of horse-chestnuts and complex formation with (alkyl)benzene - Google Patents

Abstract

An acid, amorphous saponin mixt. is obtd. by extracting horse-chestnuts with an alcohol/water mixt., treating the extract with an acidic cpd., treting the acid soln. for 3-10, pref. 4-5, mins. at 20-80, pref. 60-70, degrees C with active C, filtering, cooling the filtrate and treating with alkylbenzene or pref. benzene, separating the ppted. saponin-benzene complex, washing with an alcohol/H2O mixt. contg. 5-40 vol.% alcohol, pref. 10:90 EtOH/H2O, and removing the (alkyl)benzene from the complex by drying, pref. freeze-drying. The product has a high water-solubility (ca 20%) and the aq. solns. have almost unlimited stability. It has strong haemolytic activity and has antiphlogistic and vasoactive props.

Description

"Process for the production of an amorphous, acidic saponin mixture from Extracts of the horse chestnut "In the DT-AS 1 095 989 a method for the extraction of a crystallized, acidic saponin (B-aescin) from horse chestnuts described, in which the extraction solution obtained in the usual way with a cation exchanger is treated in the Rr form. After the cation exchanger has been separated off the acidic solution was concentrated by distillation and the crystalline precipitate formed severed.

Pure, acidic aescin is only about 0.01 percent soluble in water. By converting this saponin into the salt form, it is true that the water solubility becomes increased, but no therapeutically usable absorbability obtained. In the DT-AS 1,282,852 describes a process according to which crystalline, acidic aescin is carried out 50 hours of grinding (micronizing) in a ball mill in the X-ray amorphous add tand is convicted. The water solubility of the aescin was after grinding about 2 percent. The aqueous solution, however, is at neutral pH only some Hours stable.

The object of the invention was to provide a new, simple method for production to scoop an amorphous, acidic saponin mixture from extracts of the horse chestnut, that a considerable water solubility in the physiological pH range. These The object is achieved by the invention.

The invention therefore relates to a method for obtaining a amorphous, acidic saonine mixture from horse chestnut extracts by extraction the seeds with an alcohol-water mixture and treat the alcohol-water extract with an acidic compound, which is characterized by the fact that the acidic solution for 3 to 10 minutes at temperatures of 20 to 80 ° C. with activated charcoal treated and filtered, the filtrate after cooling with benzene or an alkylbenzene added, separates the saponin = benzene complex that is deposited with an alcohol-water mixture with an alcohol content of 5 to 40 percent by volume washes and the benzene or alkylbenzene removed from the saponin-benzene-romaplex by drying.

for the production of an acidic, amorphous saponin mixture are im Method of the invention crushed, dried horse chestnuts with a water-miscible Alcohol with a pyozent water content of 30 to 70 is extracted. The alcohol-water extract is made either by concentration or by diluting with water to an alcohol content discontinued from 207, this solution is treated with an acidic compound, whereby the saponin mixture is converted into the acidic form. The solution can e.g.

crosslinked with a mineral acid or an organic acid will, until the pH of the solution is 2-3. Preferably the solution is with a Treated cation exchanger fti the H4 form. After separating the cation exchanger the acidic solution is 3 to 10 minutes, preferably 4 to 5 M minutes, at 20 to 80 ° C, preferably 60 to 700C, treated with activated charcoal and then filtered.

It has been found that, surprisingly, the saponin mixture from the filtrate obtained by adding benzene or an alkylbenzene, e.g. Toluene or xylene, deposited as an amorphous saponin-benzene complex. Preferably the saponin mixture is separated out by adding benzene.

The saponin-benzene complex is obtained by colation, filtration or centrifugation separated and served with an alcohol / water mixture with an alcohol content of Washed 5 to 40 percent by volume.

The saponin-benzene complex is preferably mixed with an ethanol-water mixture Washed with an ethanol content of 10 percent by volume.

After washing, the saponin-benzene complex lies as a white product before, from which the benzene is removed by drying.

Preferably the benzene is removed by freeze drying. The freeze drying is carried out at a pressure below 4 torr.

The saponin-benzene complex contains 15 to 20 percent saponin.

Depending on the quality of the Rosskaatanien used as raw material 2 to 3 percent by weight of dried saponin mixture are obtained from these.

The amorphous, acidic saponin mixture produced by the process of the invention is surprisingly readily soluble in water in the physiological pH range. The limit solubility in water is about 20 percent. The aqueous solutions are practically unlimited stable. The saponin mixture produced by the process of the invention is potent hemolytic. It is suitable for the treatment of edema and has pronounced anti-inflammatory properties and vasoactive properties. The saponin mixture is therefore used to produce more valuable products Medicinal preparations, which in a known manner, optionally with the usual, pharmacological compatible carriers and / or diluents can be prepared. The medicinal products can be administered in the usual forms, e.g. in the form of tablets, Dragees, ointments, gels or injection solutions can be used. The administered Daily doses of the saponin mixture prepared by the method of the invention for tablets or dragges 20 to 100 mg, for ointments or gels 30 to 100 mg and for injection preparations 2 to 10 mg.

The examples illustrate the invention.

Example 1 100 kg of crushed, dried horse chestnuts are mixed with extracted from a hot i4Sthanol-water mixture with a methanol content of 50 percent. After separating the residue (42 to 45 kg) the methanol-water extract is under evaporated under reduced pressure to an extract content of 50 percent. The concentrated one The extract is made with the same volume of an ethanol-water mixture with an ethanol content moved from 207. the se solution is with 10 kg of a cation exchanger stirred in the H + form for 20 to 30 minutes. The solution is then released from the cation exchanger decanted or filtered and twice with 20 liters of an ethanol-water mixture Washed with an ethanol content of 20 percent, the combined solutions are after heating to 60 to 700C, 1 kg of activated carbon is added. This mixture will Stirred for 4 to 5 minutes. The activated carbon is sucked through the mixture a fine-pored pilter separated.

After cooling, 9 to 10 liters of benzene are stirred into the filtrate. After 2 hours, the white-yellow precipitated on the surface of the mixture becomes Separated mass. This can be done by colation, filtration or centrifugation. Then the mass is twice with 40 liters of an ethanol-water mixture Treated with an ethanol content of 10 percent and carefully squeezed out. the The white mass obtained in this way is freeze-dried. Be after freeze drying 2 to 3 kg of the acidic amorphous saponin mixture from Sp. 214 to 21800 obtained. The specific rotation value is [α] D20 = 180 + 20 (methanol c = 2).

The hemolytic index (determined according to Büchi et al., Pharm.

Acta Helv., Vol. 25 (1950), p. 243) is 50,000 to 60,000.

The toxicity in mice is DL 50 = 5.1 mg / kg body weight i.p.

Example 2 That according to Example 1 after separating off the activated carbon The resulting filtrate is cooled and 9 to 10 liters of oluene are added. After 2 hours the white-yellow mass deposited on the surface of the mixture is separated off. The water is processed according to Example 1. There will be 2 to 3 kg of the acidic, amorphous Preserved saponin mixture.

Example 3 Preparation of an ampoule solution A batch of 10 kg contains: 10 g saponin mixture, 88 g NaCl per injections, q.s. NaOH and ad 50 kg for Injection grade water.

The solution is prepared according to the usual pharmaceutical methods and filled under sterile conditions in accordance with the applicable regulations.

EXAMPLE 4 Production of dragees One dragee contains: 20 mg saponins mixture, mg starch, 265 mg lactoso, 4.5 mg talc and 0.5 mg magnesium stearate 100.0 mg The coated tablets are produced according to the usual pharmaceutical methods.

Claims (6)

P a t e n t a n s l) return 1. Process for obtaining an amorphous, acidic saponin mixture from extracts of horse chestnut by extracting the seeds with an alcohol lass He mix and treat the alcohol-water extract with an acidic reactant Compound, d u r c h e k e n n n z e i c h n e t that one is the acidic solution 3 to 10 minutes at temperatures of 20 to 80 0C treated with activated carbon and filtered, the filtrate is cooled with benzene or an alkylbenzene, The separating saponin-benzene complex is separated with an alcohol-water mixture with an alcohol content of 5 to 40 percent by volume washes and the benzene or alkylbenzene removed from the saponin-benzene complex by troclmen. 2. The method according to claim 1, characterized in that the acidic solution treated with activated carbon for 4 to 5 minutes at temperatures of 60 to 70 ° C. 3. The method according to claim l and 2, characterized in that one benzene is added to the filtrate after cooling. 4. The method according to claim 1 to 3, characterized in that the saponin-benzene complex with an ethanol-water mixture with an ethanol content of 10 percent by volume washes. 5. The method according to claim 1 to 4, characterized in that the benzene is removed from the saponin-benzene complex by freeze drying. 6. Medicinal preparations, marked by a content of the saponin mixture according to claims 1 to 5 and optionally customary, pharmacologically acceptable Carriers and / or diluents.