Abstract:
This invention relates to the preparation of an extract of Inula and related species such as Inula Viscosa and Inula graveolens (which belong to the family compositae) which is useful in therapy, in particular as bacteriostatic and fungistatic agent. 
     This extract is useful in the treatment of human beings suffering from infectious diseases.

Description:
BACKGROUND OF THE INVENTION AND PRIOR ART 
     Species of Inula are well known plants of the family compositae which have been described by G. GARNIER in &#34;Ressources Medicinales de la Flore Francaise&#34; vol. 2, page 1358 (Vigot Freres ed., Paris, 1961). Chemical components of several Inula species have been disclosed in Phytochemistry 17, 1165 (1978). 
     Inula viscosa and Inula graveolens which grow in the Mediterranean basin are so similar that they can be distinguished only when they are flowering. 
     It has been disclosed by G. CALDES et al., in Planta Medica 27, 72-76 (1975) that extracts of Inula graveolens (obtained by extraction with hot and respectively cold water and lyophilization) tested as antibacterial agents against Staphylococcus aureus and Streptococcus faecium and as antimalarial agents against Plasmodium berghei, are inactive. 
     SUBJECT OF THE INVENTION 
     The subject of the invention is to propose a new method of extraction of Inula in order to obtain an extract which is useful in the treatment of infectious diseases as bacteriostatic and fungistatic agent. 
     DETAILED DESCRIPTION OF THE INVENTION 
     According to the present invention, the entire plant (that is to say the stems, the leaves, the floral apices, the fruit and the roots) or a part of the plant, is extracted with at least one solvent. The product thus obtained is then purified, if necessary, and recovered according to a method known per se, 
     The extraction can be carried out by using, per liter of solvent, 30 to 150 g of ground dry plant. Solvent which can be used include alcohols (such as methanol, ethanol, propanol and isopropanol), ketones (such as acetone, methyl ethyl ketone and methyl propyl ketone), ethers (such as dimethyl ether, diethyl ether and diisopropyl ether), esters (such as ethyl acetate), hydrocarbons (such as pentane, hexane, cyclopentane, cyclohexane, petroleum ether and benzene), halogenated hydrocarbons (such as chloroform and methylene chloride), and mixtures thereof. 
     The best mode for carrying out the invention consists in extracting an Inula species selected from the group comprising Inula viscosa and Inula graveolens, with a solvent selected from the group comprising diethyl ether, ethyl acetate, ethanol and chloroform, the preferred solvents being diethyl ether, ethyl acetate and ethanol. Preferably the extraction is carried out on the entire plant ground and dried (in an oven at 37° C.). 
    
    
     The following examples illustrate the invention. 
     EXAMPLE 1 
     Total extract of Inula viscosa 
     200 g of the whole plant of Inula viscosa are dried in an oven at 37° C., ground, and extracted with 3 l. of ethanol in a Soxhlet apparatus for 4 hours. The insoluble material is discarded and the ethanol solution, after drying over anhydrous sodium sulphate, is evaporated to dryness under reduced pressure. 8 g of a soft extract are obtained (yield 4% by weight with respect to the starting plant material). 
     EXAMPLE 2 
     Total extract of Inula viscosa 
     By using chloroform instead of ethanol the material disclosed in Example 1 gives 8 g of a soft extract. 
     EXAMPLE 3 
     Total extract of Inula viscosa 
     200 g of the whole plant of Inula viscosa are dried in an oven at 37° C., ground, and extracted with 3 l. of diethyl ether at 5° to 12° C. for 48 hours. The insoluble material is discarded and the diethyl ether solution is evaporated to dryness under reduced pressure. 6.3 g of a soft extract (which is coded as C.94) are obtained. Yield=3.1% by weight with respect to the starting plant material. 
     The extracts of Examples 1 to 3 give, by thin layer chromatography the very same three spots, under the following operating conditions: 
     
         ______________________________________support     silica;mobile phase       hexane - chloroform - methanol (3:9:1       v/v/v);developer   sulphuric acid - vanillin (1 g of vanillin       per 100 ml of concentrated H.sub.2 SO.sub.4 of       density 1.84);______________________________________ 
    
     EXAMPLES 4 TO 6 
     Total extracts of Inula graveolens 
     By treating 200 g of the whole plant of Inula graveolens which have been dried in an oven at 37° C. and ground, according to the methods described in Examples 1 to 3, three soft extracts of Inula graveolens are respectively obtained with the same yields. 
     EXAMPLE 7 
     Total extract of Inula viscosa 
     400 g of the whole plant of Inula viscosa are dried at 37° C. in an oven, ground, and extracted with 3 l. of diethyl ether in a Soxhlet apparatus. The insoluble material is discarded and the diethyl ether solution, after drying over anhydrous sodium sulphate is evaporated to dryness under reduced pressure. 7 g of a total extract are obtained (yield: 1.75% by weight with respect to the starting plant material). 
     EXAMPLE 8 
     The total extract of example 7 subjected to a column chromatography [the column being filled with silica (&#34;Kieselgel 60&#34; manufactured by Merck and Co.)], gives four fractions (F1-F4) as indicated in Table I. 
     
                       TABLE I______________________________________Eluent           Fraction    Yield.sup.(a)______________________________________Hexane-methylenechloride (50:50 v/v)            F1          0.25%Hexane-methylenechloride (50:50 v/v).sup.(b)            F2          0.10%methylene chloride            F3          0.10%methylene chloride-methanol (99:1 v/v)            F4          0.12%______________________________________ Notes: .sup.(a) by weight with respect to the plant. .sup.(b) F2 requires a longer period of time then F1 to be eluated. 
    
     The extracts of examples 1-7 according to the invention exhibit bacteriostatic activity against gram (+) and gram (-) bacteria and a fungistatic activity against fungi. In particular the extract of Example 3 exhibits the MIC values given in Table II. 
     
                       TABLE II______________________________________ Microorganism        MIC (μg/ml)______________________________________Staphylococcus aureus London                  1Escherichia coli      33Proteus               33Aspergillus niger      3______________________________________ 
    
     The invention includes within its scope a therapeutic composition comprising, in association with a physiologically acceptable excipient, a pharmaceutically effective amount of an extract of the invention. Such a composition can be administered orally, locally or by injection.