OA10414A - Aromatic composition based on olibanum combined with a synergic agent (e g eucalyptol borneol zinc salt copper salt) and use thereof - Google Patents

Abstract

The present invention concerns the general field or aromatic compounds derived, in particular, from essential oils or plant essences. An aromatic composition comprises at least one active olibanum aromatic system consisting of, firstly, at least one olibanum essential oil and/or one or more components thereof and, secondly, at least one synergic agent selected from the compounds of formula C10H180 and/or one metal selected from copper and zinc salts.

Description

( îs - Amcndmcnt of 30 Octobcr 1996 * in rcsponsc (o (lie lst written opinion of 2/07/96

AROMATIC COMPOSITION BASED ON OLIBANUM COMBINEDWITH A SYNERGISTIC AGENT (e.g. EUCALYPTOL, BORNEOL, ZINCSALT, COPPER SALT) AND USE THEREOF

5 TECHNICAL FIELD

The présent invention relates to the general field of the aromatic compoundswhich are contained particularly in essential oils or plant oils.

The prime function of such compounds is obviously to release pleasant and 10 pronounced odors and tastes, so some of them are very naturally and verycommonly employed in the field of food flavoring or perfumery. However, thesecompounds can also possess therapeutic, antiseptie, disinfecting, deodorizing oreven antiparasitic and insecticidal/insect repelling properties, these properties beingutilized in industrial and commercial products where appropriate. 15 More precisely, the présent invention relates to an aromatic composition comprising at least one aromatic active principle based on olibanum, which consistsof at least one essential oil of olibanum or one or more components thereof.

The présent invention further relates to the use of such a composition for thepréparation of drugs, health care and hygiene products, disinfecting, deodorizing, 20 antiseptie, insecticidal, insect repelling or antiparasitic products, plant protectionproducts, cosmetic products or perfumes, inter alia.

PRIORART 25 The essential oil of olibanum - olibanum - (incense) is extracted from plants of the Burseraceae family. These plants, whose countries of origin are mainly thoseof North-East Africa, Arabia and Iran, produce a gum-resin which contains sugars,alcohols and acids. Conventionally the essential oil is obtained by steam distillationof this gum-resin. The distillate consists of a viscous liquid which can be colorless, 30 pale yellow, yellowish or reddish-yellow, depending on its origin and thepurification treatments to which it may be subjected. 010414 010414 _ Amendmcnt of 30 Oclobcr 1996 in rcsponsc to thc lst writtcn opinion of 2/07/96

Incense is obviously used for its pleasant odoriferous and aromatic properties, which develop especially under the action of heat. Incense has also been incorporated in opium-containing cynoglossum pills, in mercurial plasters or in préparations active against certain forms of neuralgia. The following therapeutic applications are also known for essential oil of olibanum: - internai and extemal use for the treatment of infectious States, - internai use as an antidepressant, - use as a basis for the production of stimulants and balsamics.

In addition, of course, it owes its use in perfumery to its pleasantodoriferous character.

However, the industrial and commercial exploitation of essential oil ofolibanum or its aromatic components has always remained extremely limited anddiscreet. Moreover, most of these applications in pharmaceutics, cosmetics orperfumery are no longer in use.

There are several reasons for this obsolescence, which will be examined below.

Firstly, essential oil of olibanum suffers from the disadvantage of having apoor solubility in the conventional organic solvents used in pharmacy or perfumery.This considerably hinders the manipulation of this oil and the convenientincorporation of different forms thereof into various préparations.

Moreover, a direct conséquence of this lack of solubility is a poorerdiffusion, both extemal and internai, in therapeutic use. This means that thebioavailability of the active principles of olibanum cannot be maximized and hencethat these therapeutic performance characteristics are affected accordingly.

Secondly, olibanum oil has an unfortunate tendency to dégradé on ageing, inparticular when it is exposed to aggressive environmental factors such as air, lightand heat. This results in oxidation and “résinification”, i.e. an increase in viscosity,which merely complicates the handling and use of this oil. This phenomenon ofdégradation, especially by oxidation, is accompanied by the formation of by-products which are undesirable in terms of the sought-after effects as therapeuticagents, perfumes, déodorants, disinfectants, etc.

0104 H _ Aincndment of 30 Octobcr 1996 * in response lo the lst written opinion of 2/07/96

Thirdly, it is quite obvious that aromatic compositions of the olibanum type would hâve everything to gain, as regards their industrial and commercial value, ffom an improvement in their functional, therapeutic, odoriferous, disinfecting and other properties. With this in mind, the ultimate objective, for obvious économie reasons, is to increase the activity while at the same time reducing the dose.

There does exist a State of the art relating to the invention forming thesubject of the présent disclosure, but it only comprises non-pertinent and distantlyrelated documents which do not consider the same technical problem.

The abstract of Japanese patent application JP-A-04 149 136 of 9 October1990 discloses perfume compositions which possess a synergistic physiologicalactivity and contain at least one physiologically active essential oil and at least oneessential oil enhaneïng said activity. However, said abstract does not specify whatactivity is involved.

In a long list of so-called active and undifferentiated oils, said documentindiscriminately mentions bomeol, although this is not an essential oil. An essentialoil is actually defined by its botanic origin. Now, bomeol is not a plant but aterpenic alcohol in the solid and non-volatile State, présent in certain essential oils (itis improperly called bomeol oil in some popular works).

There is absolutely no emphasis on bomeol in said document. Moreover,for the enhancing essential oil, référencé is also made, in a long list of essential oils,to îhose originating from Boswellia and Géraniales Burseracea Commiphora. Itshould be noted that, among the latter, only a few well-defined species of Boswelliacontain olibanum gum-resin (incense), and these are not disclosed by the Japaneseabstract.

Finally, said document does not recommend any particular combinationwhich is capable of solving the technical problem mentioned above, namely thesolubility and storage stability of olibanum oil.

The article in INDIAN J. PHARMACOL., 24(2), discloses double-blindcrossover clinical trials, with placebo control, of the Indian médicinal formulation“AZURVEDIC”, which comprises not only essential oils but also a root of theWithania somnifera type, a resin-gum derived from Boswellia serrala, a rhizome

Aniendmcnt of 30 October 1996 in response io the lst writtcn opinion of 2/07/96 010414 3 bis derived from Curcuma longa and a complex containing zinc, in the treatment ofrheumatoid arthritis. In reality, this formulation is an “infusion” in thepharmaceutical sense of the word, i.e. a mixture of dried and divided plants or partsof plants, to which salts are sometimes added.

Said article makes no reference whatsoever to the problem of thesolubilization and stabilization of compositions based on essential oil of olibanum.Finally, it should be noted that it is not this resin which acts as the essential activeprinciple in this clinically tested formulation. The teaching of said document is notlikely to help in the search for a solution to the problem of solubilization,stabilization and optimization of the properties of essential oils based on olibanum.

The article in J. ETHNOPHARMACOL., 33 (1-2), 1991, 91-96, relates tothe same infusion or médicinal formulation as that studied in the document referredto above. This time, however, the intended therapeutic treatment is osteoarthrosis.Said document therefore has no fürther contribution to make in assessing thepatentability of the invention which will be presented below.

DISCLOSURE OF THE INVENTION

In this situation, one of the essential objectives of the présent invention is toprovide an aromatic composition based on active compounds of olibanum andhaving physicochemical properties, particularly solubility and ageing stability, whichis improved and more adapted to the industrial demands of simplicity of use andlong shelf life.

Another objective of the invention is to provide an aromatic compositionbased on olibanum or the like which has maximum fùnctional properties, especiallyin pharmaceutics, cosmetics, perfumery or hygiene, at the lowest possible activedoses.

Another objective of the invention is to provide an aromatic compositionconstituting a starting material which is not only effective and économie but canalso be used easily and universally in a multiplicity of applications.

To meet these and other objectives, the Applicant has succeeded in 3 ter 010414

Amcndmcnt οΓ30 Octobcr 1996in responsc to thc Ist writtcn opinion of 2/07/96 demonstrating, totally surprisingly and unexpectedly and after much research andexpérimentation, that the active compounds of olibanum should be associated withat least one synergistic agent selected ifom the compounds of the formula CioHigOand/or métal salts. 010414

Amcndmcnt of 30 Octobcr 1996 in rcsponse to tlic ls( written opinion of 2/07/96

Thus the présent invention relates to an aromatic composition comprising: - on the one hand at least one active aromatic System based on olibanum andconsisting of: □ at least one essential oil selected from those extracted from the gum-resin(incense) derived from plants of the Burseraceae family which are capable ofproducing said gum-resin, these plants preferably being selected from the groupcomprising Boswellia carterii Birdwood, Boswellia Fereana Birdwood,Boswellia bhau-dajiana Birdwood, Boswellia papyrifera (Del) Hochst, Boswelliasacra Flueckiger, Boswellia serrata Ro and mixtures thereof, □ and/or one or more components of this essential oil; - and on the other hand at least one synergistic agent selected from the compoundsof the formula CioH]gO and optionally from salts of the following metals: Cu, Ag,Au, Zn, Cd and Hg, zinc and copper being parti cularly preferred.

The advantage and value of this composition lies in thé enhancement of thephysicochemical and functional properties of the active aromatic System based onolibanum by this particular Chemical class of aromatic and/or metallic synergisticcompounds. This is represented especially by: - a synergy of action, - a better solubility in organic solvents, especially in éthanol, and in aromaticcomponents, - a better diffusion - and a greater ageing stability.

This novel association is of definite industrial and commercial value for ailaromatic plant products derived from olibanum.

The essential oil of olibanum - olibanum (incense) which is more particularlyselected according to the invention is extracted from small trees of the Burseraceaefamily, preferably Boswellia carterii - birdw and similar species. These small treesgrow mainly in Iran, India, Africa and Arabia, on either side of the Red Sea andIndian Océan. The African locations are the Hom of Africa, Ethiopia, Somalia, theisland of Socotra and Eritrea, where Boswellia carterii birdwood, Boswelliafi-ereana birdwood (or female incense) and Boswellia bhau-dajiana birdwood (or 010414 4 blS Amcndmcnt of 30 Octobcr 1996 in response (o tlic lst written opinion of 2/07/96 frankincense) are found. Boswellia papyrifera (Del.) Hochst is said to grow inSudan and Eritrea. Boswellia sacra Flueckiger are found in Arabia. Boswelliaserrata Ro is found in India. Ail the Boswellia which hâve just been cited above,and which the Applicant has succeeded in isolating and selecting, produce a gum- 5 resin which contains sugars, 010414 - alcohols: olibanol, bomeol, famesol, octanol, incensol (Eritrea) ... - ethers: 1,8-cineole - carbonyl compounds: carvone, verbenone ... - a- and β-boswellic acids ... - esters: octyl acetate (prédominant constituent: up to 50% or more inEritrea).

Native or esterified bomeol, and cineole, are présent in small proportions inessential oil of olibanum, being on average more or less 1% in Eritrea and Aden.

There is an olfactory unit for gums-resins-incense and their extractionproducts.

Several technologies can be used to extract the components of olibanumresins, e.g. steam distillation, volatile solvents, thermolyzates.

These three techniques are preferred according to the invention, but steamdistillation of this gum-oleoresin is particularly preferred. The distillate consists of aviscous liquid which can be colorless, pale yellow, yellowish or reddish-yellowaccording to the origin and the treatments to which it may be subjected. Thedensity of this olibanum oil varies from about 0.850 to 1060. Its density increasesthe more it resinifies or the more resinous it is.

According to a preferred characteristic of the invention, the synergisticagent is at least partly of an aromatic nature and comprises eucalyptol, bomeol(native or esterified) or a mixture thereof. These two compounds are CioHjgOisomers which are widely available and relatively inexpensive.

Eucalyptol, which is also known as 1,8-cineole or 1,8-epoxy-p-menthane, isan internai ether corresponding to terpinol. It can be extracted in liquid form from avariety of plant oils. It is of course eucalyptus oils which contain the greatestamount of eucalyptol, namely up to 85%. Examples which may be mentioned areEucalyptus globulus, Eucalyptus austrialana, Eucalyptus amygdalina, Eucalyptuspolybractea and Eucalyptus smithii, inter alia.

Malaleuca leucadendron and Malaleuca viridiflora, which respectivelycontain from 60 to 75% and from 35 to 70% of eucalyptol, may also be mentioned.Finally, Artemisa cina and Artemisa vulgaris may be indicated by way of interest. 010414

Eucalyptol is a colorless mobile liquid with an odor reminiscent of both mint and camphor; its density is 0.921. The known pharmacological activities of eucalyptol are those of a potent expectorant and antiseptie. It is used especially as a means of combating infections of the respiratory System and urogénital System in particular.

Uses as a disinfectant, déodorant, antiparasitic or insecticide/insect repellenthâve also been recorded.

The eucalyptol useful as a synergistic agent within the framework of theinvention can be in the pure form or be introduced via an essential oil which is richtherein, for example one or more of the essential oils mentioned above.

As far as bomeol is concemed, it may be pointed out that this is an alcoholproduced by a tree growing in Bornéo and Sumatra: Dryobalanops Camphora.Bomeol (dextrorotalory camphol}, which is also known as 1,7,7-trimethylbicyclo-[2.2.1]heptan-2-ol, is collected in crystalline form from undemeath the bark ofDryobalanops camphora.

Bomeol is soluble in éthanol and fluid plant oils. Its density is less than thatof water. It is présent in a variety of plant oils, either in the pure form or in theform of an ester. The following may be mentioned as an illustration of these oilswhich are sources of bomeol: - Rosmarinus Offîcinalis (15% by weight) - essential oils of pine, and more particularly: * Abies sibirica (40% by weight of bomyl acetate) * Tsuga canadensis, * Pinus silvestris, * Pinus mariana etc. - Origanum majorana (85% by weight of a mixture of camphor and bomeolcalled “Bruylants”) - Thymus satureoides (35% by weight).

Bomeol is an antiseptie and, for many authors, a general tonie and morespecifically a stimulant of the suprarénal cortex. It is used in the treatment ofinfectious diseases and dépressive States or as a desensitizer. 010414

In the same way as for eucalyptol, a borneol-based synergistic agent can be introduced into the aromatic composition of the invention via one or more essential oils, including especially those mentioned above which are rich in this active aromatic compound.

Given that the aromatic compositions according to the invention can beobtained especially by using ail or some of the essential oils of olibanum as well asessential oils containing eucalyptol and/or bomeol, it is interesting to point out thatthese plant oils can vary in their composition, said variations depending on severalfactors. First of ail, it is obvious that the living plant from which these oils originatedétermines a variability related to the géographie location, on which the climate andthe nature of the soil dépend. Furthermore, the composition can change as afunction of the time at which the plant is harvested. Finally, it is clear that thedistillation and the manner in which it is carried out are other factors with someinfluence on the essential oil obtained in fine.

Considering these factors, it should be noted that the first is not reallycrucial and that the other two can be controlled so as to ensure a constancy of theproperties, especially the physicochemical, therapeutic and cosmetic properties, ofthe essential oils.

It should also be considered that said essential oils can be in a rectified ornon-rectified form for use in the aromatic compositions according to the invention.

Thus, within the framework of the présent invention, the term “rectified”refers to one or more purification treatments by means of which one or more of theundesirable components are removed from the essential oils. In particular, terpenes,which are présent in practically ail essential oils, can be removed by deterpenation.The aim of such a treatment is to improve the solubility of the oil in éthanol andimprove its aromatic power. This relates more specifically to perfumery. It is self-evident that the purification or rectification of the oil can also extend to oilconstituents other than terpenes, namely alkaloids or other non-terpene component.

These purification/rectification treatments make it possible to remove thetroublesome compounds in accordance with the intended use. These troublesomecompounds can be totally or partially removed in this way. 010414

In the case where the active System based on olibanum consists of at leastone essential oil of olibanum, and where the synergistic agent comprises eucalyptol,the latter is preferably présent in a proportion of 15 to 75% by volume, preferably25 to 35% by volume, relative to the total composition.

On the other hand, if the active aromatic System based on olibanum consistsof at least one essential oil of olibanum, and if the synergistic agent comprisesbomeol, the proportion of the latter is 5 to 100% by weight, preferably 20 to 30%by weight and particularly preferably about 25% by weight, relative to the activeSystem based on olibanum.

The composition advantageously contains at least one organic solventselected ffom fatty substances, alcohols, ethers and mixtures thereof, preferablyfrom alcohols and/or ethers, éthanol being more particularly preferred.

In an advantageous variant of the invention, the synergistic agent comprisesat least one métal sait présent in an amount such that the métal cation(s) represents(represent) from 0.1 to 10% by weight, preferably 0.1 to 5%, relative to the totalweight of aromatic compounds forming the aromatic substance.

The synergistic agent preferably comprises at least one zinc sait and/or atleast one copper sait.

In the case where the cation originates ffom copper, its concentration,expressed in % by weight relative to the total weight of aromatic compounds (oraromatic substance), is advantageously between 0.3 and 1%, preferably between 0.4and 0.6%.

In the case where the cation originates ffom zinc, its concentration,expressed in % by weight relative to the total weight of aromatic compounds (oraromatic substance), is advantageously between 0.1 and 2%, preferably between 0.5and 2%.

The synergistic combination of the System based on olibanum, on the onehand, and eucalyptol and/or bomeol and possibly Zn and/or Cu sait, on the other,has the advantageous effect of increasing the solubility of the olibanum compoundsin organic solvents such as, for example, éthanol. This proves to be the caseespecially for essential oil of olibanum, whether it be in rectified or non-rectified 010414 form and whatever the extraction procedure may be.

It is also found that the composition diffuses much better, compared withthe aromatic composition based on olibanum alone, through various solid substratessuch as animal or plant tissues and fibrous materials (when the composition is in theliquid or gaseous State) and through gases such as air (when the composition is inthe vapor State).

This excellent diffusion is the basis of better performance characteristics interms of bioavailability and hence therapeutic efficacy, and also as regardsperiùmery, cosmetics, disinfection or deodorization of the ambient air.

It has also been possible to observe that the synergistic combinationdescribed above confers particularly optimized storage stability properties.

The invention can be carried out according to different embodiments. - a - According to a first embodiment, rectified or non-rectified essential oilof olibanum is mixed with pure (or substantially pure) synergistic agent such aseucalyptol and/or bomeol. Examples of possible proportions are thus: - 30% by volume of essential oil of olibanum (rectified or non-rectified) - and 70% by volume of eucalyptol;or: - 75% by weight of essential oil of olibanum (rectified or non-rectified) - and 25% by weight of bomeol;or finally: - 30% by volume of essential oil of olibanum (rectified or non-rectified), - 70% by volume of eucalyptol - and 25% by weight of bomeol, relative to the essential oil of olibanum. - b - In a second embodiment, the composition can consist of a mixture ofessential oils constituting a vehicle for the essential active principles of theinvention, namely the olibanum compounds and the synergistic agent based oneucalyptol and/or bomeol and possibly on at least one métal sait. In this particularcase, the essential active principles of the invention (olibanum and synergisticagents) are naturally still présent in the same proportions as those referred to above.In practice, said composition can be for example a mixture of rectified or non- 010414 10 rectified essential oils of olibanum with rectified or non-rectified essential oils rich ineucalyptol and/or bomeol, preferably those mentioned above. The chosen essentialoils rich in bomeol can be those which contain bomeol in the native State. Now, thelatter possesses particularly valuable solubilizing properties compared with bomeolin the form of esters; by contrast, the performance characteristics of bomeol esterscan be exploited for their therapeutic properties.

It is thus possible to adjust the respective proportions of native bomeol andbomeol esters according to the intended final applications: + in a first variant, the therapeutic properties (synergy) can be favored byenriching the composition in bomeol esters; + in a second variant, the solubilizing properties (perfumery) can beexploited by increasing the amount of native bomeol; + and in a third variant, both types of properties can be utilized. - c - Without implying a limitation, and by way of a third embodiment, it isalso possible to consider the alternative whereby one or more components ofolibanum oil are selected, including the alcohols, like olibanol, and the acids. Thiscan be achieved by employing fractional distillation as well as other methods ofpurification which afford deterpenation, the conséquences of which are to limit theamount of the components and increase the proportion of acids and alcohols or of apreferred component, for example octanol as the alcohol or in the form of an esterlike octyl acetate, in Eritrean olibanum oil.

In said alternative, the component(s) of essential oil of olibanum areadvantageously associated either with eucalyptol or with a mixture of eucalyptoland bomeol (in the pure form or in the form of essential oil(s)).

Thus the component(s) preferably represents (represent) between 5 and60% by weight of a composition comprising the component(s) and eucalyptol, a concentration of 15% by weight being particularly preferred.

Preferentially the associated synergistic agent is eucalyptol, although thisdoes not exclude eucalyptol/bomeol mixtures. In the latter cases, the concentrationof bomeol is between 10 and 50% by weight, preferably 25% by weight, relative tothe mixture of eucalyptol and chosen olibanum component(s). This corresponds to 010414 11 e.g.: - component(s) originating from essential oil of olibanum (15% by weight),) - eucalyptol (85% by weight), / - optionally bomeol, 25% by weight of x.

Given that: the more resinous the total ohbanum oil is, the greater is its solubility in organicsolvents such as éthanol, and this phenomenon tends to disappear with the rectified oil,it is possible to envisage using resinous, non-rectified, total essential oil of olibanumto détermine a maximum solubility. This enables the therapeutic properties of thecomposition to be improved.

Conversely, a rectified, non-resinous essential oil of olibanum can beemployed especially for application in perfumery, and it can be associated withbomeol and/or eucalyptol for enhanced diffusion and stability and better solubility inorganic solvents.

Within the framework of the advantageous variant of the invention referredto above, the activity of the essential oil of olibanum and/or one or morecomponents of said essential oil, and their association with bomeol and (or)eucalyptol, is enhanced with the aid of at least one métal sait, the preferred metalsbeing zinc and copper. They appear in the pharmacopeia as sédatives for thenervous System (neuralgia, epilepsy, spasm) and antiseptics. They hâve the sametherapeutic purpose as the aromatic components with which it can be associated.Even more preferably, they consequently act in synergy with these aromaticcomponents. The novelty consists in associating for example one (or two) métal viaa minerai sait such as zinc chloride or cupric chloride, or an organic sait such as zincacetate and copper acetate. The percentage of the elemental métal (or metals) isbetween 0.1 and 10% by weight of the aromatic substance consisting of theessential oil of olibanum or one or more of its components, associated with bomeoland (or) eucalyptol. The percentage of zinc is preferably between 0.5 and 2% andmore preferably 1.4% by weight. The percentage of elemental copper is preferablybetween 0.3 and 1% and more preferably 0.5% by weight.

In practice, in this variant, both metals are associated with the aromatic 010414 12 substance. The percentage of the sum of the two metals (elemental métal) ispreferably less than or equal to 2% by weight of the aromatic substance.

The essential oil of olibanum can thus act as an excipient or intermediateexcipient by diluting the bomeol and the métal salts, which are in the solid State, thewhole forming a stable product.

The composition according to the invention, which associâtes essential oil ofolibanum or one or more of its components with eucalyptol and (or) bomeol as wellas a zinc sait and (or) a copper sait, can be used pure or together with an aromaticor non-aromatic additive for use in drugs, cosmetics or hygiene products. In thiscase, the different compositions hâve a complementary rôle.

In fact, when carrying out polytherapy for example, it is easier to use asingle préparation than several préparations. In this case, several compositions arein one and the same solution or form part of one and the same galenical form. Apharmaceutical manufacturer who is interested in the présent invention and wishesto associate it with an existing or future aromatic or non-aromatic drug canincorporate it into one and the same préparation with said drug. The same appliesto a manufacturer of cosmetic and hygiene products.

The composition according to the invention, with or without an additive,can be used with excipients, preferably fatty substances and particularly preferablyethers and alcohols, éthanol being preferred, and with various pharmaceuticalpréparations and forms.

Advantageously, at least one other aromatic or non-aromatic ingrédient canbe added to the compositions according to the invention.

INDUSTRIAL APPLICATION

According to another of these features, the invention relates to the use ofthe above-defined composition especially in the préparation of drugs (e.g. anti-infectious agents, antiseptics, antidepressants, stimulants, desensitizers) for internaiand/or extemal use (as appropriate), health care and hygiene products, disinfectant,déodorants, cosmetic products, perfumes or plant protection products. 13 010414

Finally, the présent invention relates by way of novel products to e.g.: + drugs (e.g. anti-infectious agents, antiseptics, antidepressants, stimulants,desensitizers), + perfumes, + cosmetic products, + health care and hygiene products (déodorants, disinfectants),comprising the aromatic composition as described above.

BEST MODE OF CARRYING OUT THE INVENTION

The following Examples will provide a clearer understanding of theinvention and will demonstrate ail these advantages and these different non-limitingvariants. EXAMPLES:

Examples 1 to 4: Solubility t> In Example 1, préparation no. 1 below: -a - essential oil of olibanum (originating ffom Arabia)............100 g -b - dissolved bomeol.............................................................. 50 g is made up by stirring for 5 min at room température (preferably after the tube hasbeen heated gently). 20 cm3 of 70° alcohol (éthanol) solubilize 1 cm3 of préparation no. 1,whereas the same amount of essential oil - a - as that contained in 1 cm3 ofpréparation no. 1 is not solubiîized by 20 cm3 of 70° éthanol. t> In Example 2, préparation no. 2 below: - c - rectified essential oil of olibanum (originating ffom Iran).... 100 g - d - bomeol.............................................................................. 50 g is made up by following the same procedure as in Example 1. 40 cm3 of 70° alcohol solubilize 1 cm3 of préparation no. 2. The sameobservation is made as in Example 1, namely that the oil - c - without bomeol isinsoluble in éthanol. 010414 14

In general, bomeol improves the solubility of rectified or non-rectifiedessential oil of olibanum, irrespective of the origin of the olibanum. > In Example 3, préparation no. 3 below: - e - essential oil of olibanum (originating from Arabia)..... 30% by volume - f - eucalyptol.................................................................. 70% by volume is made up by following the same procedure as in Examples 1 and 2.

This préparation no. 3 is solubilized by ten (10) times its volume of 60° éthanol.

The essential oil employed on its own requires 80 times its volume of 60°éthanol to solubilize it.

Whatever its origin and whether it is rectified or non-rectified, essential oilof olibanum is solubilized remarkably by eucalyptol.

Eucalyptol increases the solubility of essential oil of olibanum in éthanol. > In Example 4, préparation no. 4 below: - g - essential oil of olibanum provided by Laboratoire MANE, originating front Ethiopia, lot no. 95/01973 ........................................................ 1 ml - h - 90% pharmaceutical grade éthanol.................................0.6 ml is made up. A turbid mixture is obtained after stirring. 4.1 The addition of eucalyptol (Coopération pharmaceutique française, lot no.A25565) in 10 μ.1 aliquots gives a slightly colored, clear solution. The total amountof eucalyptol added is 30 μΐ, i.e. 3% by volume relative to the olibanum oil used. 4.2 In a variant, borneol (Laboratoire de Combe d’Ase, lot no. HB11) is addedto the starting mixture causes clarification of the starting mixture after 5 mg ofbomeol hâve been added, and complété solubilization of the oil after 8 mg ofbomeol hâve been added (clear solution). 4.3 According to another protocol, olibanum resin (Laboratoire de Combed’Ase, lot no. HE02), in the form of chips weighed at room température, is addedto the starting mixture. The addition of 10 mg of resin does not eliminate theturbidity of the starting mixture. Heating to about 40°C, however, producescomplété solubilization. The mixture becomes turbid again after cooling to room 15 010414 température. On the addition of a fùrther 10 mg of resin, the mixture clears and a solution is obtained by very gentle heating. The solution then remains clear at room température. 20 mg of resin hâve eventually been added in order to solubilize 1 ml of essential oil.

Example 5: Oxidation of the three experimental solubilized mixtures ofExample 4 comprising essential oil of olibanum

During the 48 hours following the three experiments 4.1, 4.2 and 4.3 ofExample 4, the solubilized mixtures obtained were brought into contact with air byrepeated opening of the flasks containing them. It was possible to observe, in fine,that mixtures containing 1 ml of essential oil of olibanum, 0.6 ml of 90% éthanoland a synergistic agent formed by eucalyptol (experiment 4.1), bomeol (experiment4.2) and olibanum resin (experiment 4.3) give non-oxidized, clear solutions. It istherefore seen that these mixtures are not perturbed by oxidation, especially asregards solubilization of the essential oil of olibanum. The NMR spectra of themixtures before and after oxidation show slight différences.

Example 6: Préparation of a composition of essential oil of olibanumwith synergistic agents of aromatic and metallic type

The following composition is prepared:

The following may be mentioned as an example of this variant:aromatic substance (aromatic - Essential oil of olibanum .... 30% by volume molécules) of the = - Eucalyptol..........................70% by volume composition representing 1 g - Bomeol..............................25% by weight relative to the essential oil of olibanum - Zinc chloride.....................0.030 g - Cupric chloride..................0.015 g

Example 7: Stability

Stability is understood here as meaning constant homogeneity of the liquidcomposition (without the formation of précipitâtes). This is assessed by reactinghydrochloric acid (HCl) with the essential oil of olibanum. This causeshyperoxidation, which results in a coloration of the oil ranging from red to darkbrown, as well as a characteristic odor. There is précipitation of the most oxidized 16 010414 components and the chlorinated components.

The protocol of the test is as follows: - 1/20 cm3 of a 1/3 aqueous solution of HCI is poured into 1 cm3 of essential oil ofolibanum. The mixture is stirred for a few seconds and left to stand for a fewminutes. The aqueous solution is then separated from the supematant oxidizedessential oil. The aqueous solution has the same red color as the oxidizedessential oil because it contains oxidation and chlorination products. The oxidizedessential oil collected contains a precipitate, the amount of which increases themore resinous the oil is.

In the test with hydrochloric acid (HCl), associating bomeol or eucalyptolwith the olibanum oil results in solubilization of the precipitate.

COMMENTS

Eucalyptol and bomeol seem to stabilize the essential oil of olibanum bysolubilizing its components and its oxidation and décomposition products.

The phenomenon whereby the décomposition products of olibanum oil aresolubilized in éthanol with the aid of bomeol and eucalyptol is also verified whenthe composition comprises certain non-rectified oils as well as certain componentsof essential oils other than olibanum oil (aromatic additives).

Example 8: Diffusibility A drop of eucalyptol on a sheet of paper produces a spot which spreadsrapidly and evaporates without leaving a trace. A drop of essential oil of olibanum produces a spot which spreads slowlyand leaves a trace in the same way as fixed oils. This appears to be a particularfeature of the essential oil of olibanum compared with other oils. The spot spreadsmore slowly the more resinous the essential oil of olibanum is; a deposit then forms,the area of which is smaller than that of the spot.

If the above experiment is repeated in the presence of eucalyptol, it is foundthat the olibanum oil diffuses more rapidly and the area of the deposit is greater forthe same resinous essential oil.

The eucalyptol acts as a vehicle. This is important especially for internai andextemal use in therapeutics.

Claims (9)

17 010414 Amcndmenf of30 Octobcr 1996 in rcsponsc <o the lst writtcn opinion of 2/07/96 CLAIMS:

1. An aromatic composition comprising: - on the one hand at least one active aromatic System based on olibanum andconsisting of: □ at least one essential oil selected from those extracted from the gum-resin(incense) derived from plants of the Burseraceae family which are capable ofproducing said gum-resin, these plants preferably being selected from the groupcomprising Boswellia carterii Birdwood, Boswellia Fereana Birdwood,Boswellia bhau-dajicma Birdwood, Boswellia papyrifera (Del) Hochst, Boswelliasacra Flueckiger, Boswellia serrala Ro and mixtures thereof, □ and/or one or more components of this essential oil; - and on the other hand at least one synergistic agent selected from the compoundsof the formula CioHisO and optionally from salts of the following metals: Cu, Ag,Au, Zn, Cd and Hg, zinc and copper being particularly preferred.

2. An aromatic composition according to claim 1, characterized in that thesynergistic agent is at least partly aromatic and comprises eucalyptol, bomeol or amixture thereof.

3. An aromatic composition according to claim 1 or claim 2, characterized inthat the synergistic agent is introduced via at least one essential oil which is richtherein, said essential oil being in rectified or non-rectified form.

4. A composition according to any one of daims 1 to 3, characterized in thatthe active aromatic System based on olibanum consists of at least one essential oil ofolibanum, and in that the synergistic agent comprising eucalyptol is présent in aproportion of 15 to 75% by volume, preferably 25 to 35% by volume, of the totalcomposition.

5. A composition according to any one of daims 1 to 4, characterized in thatthe adive aromatic System based on olibanum consists of at least one essential oil ofolibanum, in that the synergistic agent comprises bomeol and in that the latter is in aproportion of 5 to 100% by weight, preferably 20 to 30% by weight and particulariypreferably about 25% by weight, relative to the active System based on olibanum.

6. A composition according to any one of daims 1 to 3, characterized in that 18 Ο 1 Ο 4 14 Amendmcnt of 30 Oetober 1996in response to the Ist written opinion of 2/07/96 the active aromatic System based on olibanum is formed by one or more components of essential oil of olibanum, in that said composition contains eucalyptol and possibly bomeol as synergistic agents, and in that said composition is quantitatively defined as follows: 5 -1- about 15% by weight of component(s) originating from essential oil of olibanum, - 2 - about 85% by weight of eucalyptol, it optionally being possible to add bomeol in a proportion of about 25% by weightrelative to the mixture 1 + 2. 10 7. A composition according to any one of daims 1 to 6, characterized in that the synergistic agent comprises at least one zinc sait and/or at least one copper sait,and in that the métal cations of this (or these) salt(s) represents 0.1 to 10% byweight, preferably 0.1 to 5%, of the total weight of the aromatic substance.

8. A composition according to any one of claims 1 to 7, characterized in that it 15 contains at least one organic solvent selected from fatty substances, alcohols, ethers and mixtures thereof, preferably from alcohols and/or ethers, éthanol being moreparticularly preferred.

9. A composition according to any one of claims 1 to 8, characterized in that atleast one other aromatic or non-aromatic ingrédient is added.

10. Use of the composition according to any one of claims 1 to 9 in the préparation of drugs, health care and hygiene products, cosmetic products,perfùmes, disinfectants, déodorants or plant protection products.