PRIOR ART It is known from literature (Martindale, "The extrapharmacopeia", 28th Ed. (1982); Cannizaro, Boll.

Soc. Ital. Biol Sperim. 1,22, 1964; V. Hoppe, Drogenkunde Bdl Walter De Gruyter Ed., 1975; and British patent 2.184.353 A) that the extracts obtained by extraction with chlorinated solvents, aliphatic ethers and ketones as well as aliphatic and aromatic esters, from the roots, the bark of the trunk and the leaves of different species of Krameria, preferably Krameria triandra, enriched in neolignanes (particularly Eupomatenoid 6 and 2-(2,4-dihydroxyphenyl)-5- propenylbenzofuran) have antimicrobial activity against gram +, gram - bacteria, fungi and anaerobic strains.

These extracts, although obtainable by extraction even with protic solvents, are naturally hydrophilic due to the phenol character of their active components.

The pure components Eupomatenoid 6 and 2-(2,4- dihydroxyphenyl)-5-propenylbenzofuran can be recovered from these extracts using chromatographic techniques on silica gel, as reported in EP 0 464 297 B1.

From the flowers, particularly from the buds, of Mesua ferrea, extraction with aprotic solvents such as

hexane, methylene chloride or better with carbon dioxide in hyper-critic conditions, for example extracting the vegetable material under pressures ranging from 110 to 260 bar, mainly at 200 bar and at temperatures ranging from 35 to 65*C, preferably at 45-C, yields a lipophilic extract containing substituted coumarins and xanthones, which results particularly active on gram +, gram - and anaerobic bacterial strains, with an activity comparable to that of the extract prepared from Krameria triandra.

DISCLOSURE OF THE INVENTION The present invention relates to a combination comprising: - a hydrophilic extract of Krameria sp., preferably Krameria triandra, or a pure compound from said extract, and - a lipophilic extract of Mesua ferrea, having antimicrobial activity.

"Pure compound from an extract of Krameria" means neolignanes such as Eupomatenoid 6 and 2-(2,4- dihydroxyphenyl)-5-propenylbenzofuran).

It has surprisingly been found that said combination, in ratios ranging from 1:10 to 10:1, preferably in a 1:1 ratio, leads to a synergism of the antimicrobial activity of the single extracts unforeseeable in advance.

The combinations of the present invention can be used also as preservatives in the alimentary and cosmetic industries. Therefore the present invention also relates to alimentary or cosmetic formulations containing as preservatives: a) a hydrophilic extract of Krameria sp., preferably

Krameria triandra, or a pure compound from said extract, and b) a lipophilic extract of Mesua ferrea.

The invention relates as well to the use of: a) a hydrophilic extract of Krameria sp., preferably Krameria triandra, or a pure compound from said extract, and b) a lipophilic extract of Mesua ferrea, as preservative for alimentary and cosmetic formu- lations.

The following table shows the average values of the in vitro antimicrobial activity of two exemplary extracts, respectively prepared from Krameria triandra, from Mesua ferrea, and those resulting from a combination in a 1:1 ratio.

Said activity, expressed in M.I.C., has been evaluated in agreement with the conventional procedures known to those skilled in the art.

Table - In vitro antimicrobial activity of the standardized extracts of Krameria triandra and Mesua ferrea.

Microbial strains M.I.C. ug/ml I II III IV Staphilococcus aureus MPR5 6.1 4 2 1 Staphilococcus aureus ATCC6538 12 7 3 0.5 Staphilococcus aureus F2 ISF 3 9 15 4 - Staphilococcus epidermis HCF Berset C 10 8 4 - Staphilococcus epidermis CPHL 8 6 3 1 Streptococcus feaecalis LEP Br 10 6 2 16 Escherichia coli CNUR 1 >128 >128 32 0.51 Acinetobacter cal. OSMPV 6.2 4 2 2 Pseudomonas aeruginosa CNUR 4 6 4.3 1 32 Trichophyton mentagrophy- tes 193 128 61 12 2 Candida albicans ATCC 10231 62.5 128 12 2 Bacteroides fragilis 26 16 4 32 Propionibacterium acnes 4 4 1 32 I = extract of Krameria triandra prepared according to example II II = extract of Mesua ferrea prepared according to example I 111= 1:1 combination of Krameria triandra and Mesua ferrea IV = rufloxacin for bacterial, miconazole for fungi.

The present invention, therefore, relates to pharmaceutical and cosmetic formulations with antimicrobial activity, which can be administered topically (gels, creams, lotions, milks and solid preparations) containing the combinations described above. Said formulations will be prepared according to conventional methods well known in pharmaceutical technique, as those described in "Remington's Pharmaceutical Handbook", Mack Publishing Co., N.Y., USA, together with suitable excipients, in particular antioxidants.

The following examples illustrate the invention in further detail.

Example I - Preparatlon of the lipoDhlllc extract of Mesua ferrea 1 kg of finely ground buds of Mesua ferrea is extracted in a 5 1 extractor with CO2 in hyper-critic conditions; a first extraction is carried out at 340C and 90 bars of pressure, using about 25 1 of carbon dioxide; the resulting extract is discarded and the vegetable material is subjected to a second extraction, increasing temperature to 45*C and pressure to 220 bar.

15.6 g of a very thick oil of orange colour are obtained. This oil can be used directly as such or subjected to further fractionations by means of conventional chemical separations.

Example II - PreDaration of the extract of Krameria triandra 2 kg of bark of the root of Krameria triandra, after grinding, are extracted three times with 5 1 each of acetone; the combined extracts are concentrated to

small volume and the concentrate is taken up in 0.8 1 of acetone:water 1:1 (v/v). The resulting suspension is extracted twice with 0.5 1 of methylene chloride, the chloromethylene phase is dried over anhydrous sodium sulfate, then concentrated to dryness. 85 g of a reddish solid are obtained, containing about 26% of Eupomatenoid 6 and 14% of 2-(2,4-dihydroxyphenyl)-5-propenylbenzofu- ran.

Example III - PreDaration of the extract of Mesua ferrea with hexane 1 kg of finely ground buds of Mesua ferrea is extracted 4 times with 3 1 of hexane under reflux; the combined hexane extracts are decolourized with active charcoal (5 g) and concentrated under vacuum to an oil.

14.5 g of extract are obtained, which can be used without further fractionation.