DE1593838C3 - Rutin tri- (dihydroxypropyl) ether and process for its preparation - Google Patents

Description

of melting point 135 ° C.

2. Process for the preparation of rutin tri- (dihydroxypropyl) ether according to claim 1, characterized in that that in a known manner 1 mole of rutin in the presence of at least 3 moles of an alkali metal hydroxide reacted in an aqueous medium with at least 3 moles of glycerol-a-monochlorohydrin and then the filtered reaction solution for purification successively over an anion and a cation active Ion exchanger conducts.

The invention relates to the rutin tri- (dihydroxypropyl) ether with a melting point of 135 ° C. of the following formula

O-

O-O

and a method for its production.

It is known that rutin has a considerable potentiating effect on peripheral blood vessels while doing so but has almost no harmful effect on the human body. This substance has therefore been used since long in therapy generally as a peripheral vasculature enhancer to avoid used for bruising in the peripheral system, high blood pressure and central hemorrhage. However, the use of rutin for injection is due to its extremely low solubility in water only possible with certain restrictions. There are water-soluble derivatives of rutin, like the tri - (p - hydroxyethyl) ether known, but these compounds are not entirely satisfactory.

It has been found that the rutin tri- (dihydroxypropyl) ether according to the invention is unlimited Has water solubility and is superior in effect to known compounds.

The reinforcing effect on the peripheral vascular system of the compounds to be tested was determined by determining the preventive capacity of blood permeability of capillary blood vessels are determined in the following way:

Various amounts of the substances to be tested were put into the abdominal spaces of males Mice of the DD breed with body weights between

/ -CH ₂ -CH-CH ₂ OH ^
OH J

Entered 17 and 23 g. After 30 minutes, 0.1 ml / 10 g body weight became trypan blue through interperitoneal Injection given. Immediately afterwards, a drop of xylene was placed on the right earlobe and the time is determined after which the dye is excreted on the area treated with xylene started.

The ratio of the elimination time of the dye in the test animals and in the control animals is given by the following equation:

in the

L = the ratio in percent of the elimination time of the dye,

A = elimination time of the dye in seconds in the test animals and

B = elimination time in seconds for the control animals

means.

The results of these tests are compiled in the table below.

Number of Tested substance dose Time to appear L "/ o Attempt mg / kg of the dye - animals Control attempt - (Sec.) 15.8 15th Rutin 100 88.9 ± 4.8 34.0 15th Rutin 200 103.0 ± 10.5 30.1 15th Rutin tri- (ß-hydroxyethyl) ether (known from 200 119.2 ± 15.7 15th German interpretation document 1 061 327) 115.7 ± 14.0 22.0 Hesperidin-methylchalcone (known from 200 15th German interpretation document 1 061 327) 108.5 ± 13.6 51.4 Hesperidin-methylchalcone (known from 200 15th German interpretation document 1 061 327) 134.0 ± 33.3 38.0 Rutin tri- (dihydroxypropyl) ether 100 73.0 15th Rutin tri- (dihydroxypropyl) ether 200 122.8 ± 17.7 15th 153.9 ± 24.1

Hesperidin-methylchalcone is z. B. in CA 47 p. 10554h and in U.S. Patent 2,615,015.

From the table it can be seen that the compound according to the invention is more than twice as vasodilatory Has an effect on the peripheral vascular system as rutin or the already known rutin tri- (ß-hydroxyethyl) ether and that it is also superior to hesperidin-methylchalcone in its effect.

The rutin - tri - (dihydroxypropyl) - ether of mp 135 ° C is produced by in itself known manner 1 mole of rutin in the presence of at least 3 moles of an alkali metal hydroxide in aqueous Medium with at least 3 moles of glycerol-u-monochlorohydrin reacted and then the filtered reaction solution for purification one after the other conducts an anion-active and a cation-active ion exchanger.

The reaction is expediently carried out in a nitrogen atmosphere and at a temperature which is between room temperature and 90 ° C. The aqueous solution of the reaction product is obtained by adding a mineral acid, e.g. B. acidified by hydrochloric acid or sulfuric acid, with gaseous Nitrogen is blown through. The acidic solution is then used to remove any existing solid substances filtered. The filtrate is concentrated by evaporation, whereby you get the connection you are looking for. A purer product is obtained if the filtrate is removed from the Evaporation passes through an anion-active and a cation-active ion exchanger.

example

61 g of rutin were suspended in 250 ml of water, and the suspension was passed through for 5 hours stirred by nitrogen. In order to dissolve the rutin, 50 ml of an aqueous and 12.5 g of a solution containing sodium hydroxide were added. After completely dissolving the rutin 35 g of glycerinra-monochlorohydrin were added to the solution with stirring added dropwise, then the solution was heated to 75 ° C for 2 hours. After cooling down the pH of the reaction mixture was adjusted to 5 using 0.1 N HCl and the mixture was im Left refrigerator for 2 days. The unreacted rutin which separated out was filtered off. The filtrate was through a column with anion-active exchanger and a column with cation-active Exchanger cleaned. After concentrating the solution, there was obtained 52 g of rutin tri- (dihydroxypropyl) ether obtained from the mp 135 ° C. The yield was 63%, based on the rutin used.

Weight analysis in percent for C ₃₆ H ₄₈ O

Calculated
found .

C 51.92, H 5.77%;
C 51.84, H 5.70%.

Claims (1)

Claims: 1. Rutin tri- (dihydroxypropyl) ether of the formula O-O O— OC ₁₂ H ₂₁ O ₉ -CH ₂ -CH-CH ₂ OH)]
OH / 3