WO2018189100A1

WO2018189100A1 - Compositions comprising essential oils

Info

Publication number: WO2018189100A1
Application number: PCT/EP2018/059014
Authority: WO
Inventors: Ezio Bombardelli; Paolo Morazzoni; Massimo Ronchi; Pietro Allegrini
Original assignee: Indena S.P.A.
Priority date: 2017-04-12
Filing date: 2018-04-09
Publication date: 2018-10-18
Also published as: IT201700040828A1

Abstract

The present invention relates to solid powdered compositions comprising at least one phospholipid and at least one essential oil deriving from citrus fruits or Lavandula officinalis. The compositions according to the invention are useful in the prevention and/or treatment of insomnia and anxiety, and in reducing appetite and stimulating the metabolism. The present invention also relates to pharmaceutical or nutraceutical formulations for oral or topical administration containing said compositions.

Description

COMPOSITIONS COMPRISING ESSENTIAL OILS

Technical field of invention

The present invention relates to solid powdered compositions comprising at least one phospholipid and at least one essential oil deriving from citrus fruits or Lavandula officinalis, which are useful in the treatment of insomnia and anxiety, and in reducing appetite and stimulating the metabolism.

Background of the invention

Anxiety, depression and obesity are among the most common disorders of the modern era, affecting a large proportion of the population ranging from infancy to adulthood.

Dysfunctions such as insomnia, states of anxiety and mild depression often occur as a result of stress, competitiveness and metabolic disorders, and their treatment requires the use of specific, potent medicaments which are inadvisable because of their side effects and the possible risk of dependence.

Sleep disorders have a significant incidence in the oncological and pre-operative fields, and are added to problems liable to cause a deterioration in the patient's quality of life.

Anxiety and depression are often directly or indirectly correlated with metabolic disorders, leading to problems in personal relationships.

Excess weight at pre- and post-pubertal age, and obesity in general, create serious problems of depression generated by contact with the opposite sex or inability to follow prescribed diets.

Excess weight is also one of the major health problems because it is positively correlated with an increased risk of numerous serious disorders, such as cardiovascular diseases, diabetes and cancer.

Anxiety, depression and insomnia are correlated with one another in the absence of specific psychiatric disorders. In adults of both sexes, insomnia is a very widespread problem, which affects a growing number of individuals of working age, between 30 and 50, as a result of stress-induced anxiety, which makes the individual tired and irascible; hence the need for non-sedative tranquillisers with a calming, sleep-inducing function which act in the most physiological way possible.

Sleep, and specifically good sleep quality, is one of the essential ingredients for a good quality of life, in order to maintain the individual's physical, social, emotional and functional well-being.

Sleep is one of the main sources of an individual's energy, especially in patients suffering from serious disorders, who are already exhausted by the illness.

Insomnia is a sleep disorder characterised by inability to sleep, even though the body has a real physiological need for sleep.

Insomnia can be defined as the subjective perception of difficulty with the beginning, duration and consolidation of sleep, leading to a reduction in its quality, which takes place despite sufficient opportunities for rest, and leads to impairment during the day.

This is associated with a poor quality of daytime life, involving symptoms such as fatigue, learning and memory difficulties, and lack of interest in everyday activities. The psychological impact on personal relationships is considerable, and the resulting irritability worsens the situation.

Unless otherwise indicated, "insomnia" refers to chronic insomnia, which has been present for at least a month; otherwise the disorder is known as acute or transient insomnia, which can last for periods ranging from days to weeks.

The symptoms of insomnia can be found in about 33% to 50% of the adult population; when associated with stress or weakness they are present in between 10 and 15%) of cases, whereas insomnia associated with specific disorders affects between 5 and

10%o of cases.

Risk factors for insomnia include aging, female sex, the presence of co-morbidities (medical, psychiatric, etc.), shift work, and the onset of devastating socio-economic situations.

The main disorders characteristic of insomnia relate to difficulty in getting to sleep, lengthy periods of waking during the night, and non-restorative or poor-quality sleep, with individual variables associated with the methods of onset, duration, frequency and perpetuation of the triggers, the type of present and past treatments used, and their efficacy.

Common problems associated with insomnia are an average sleep onset latency >30 minutes, periods of night waking with a total duration >30 minutes, and sleep duration of less than 6 hours per night.

To ensure the success of treatment, it is necessary to identify whether the patient suffers from real insomnia or a low amount of sleep due to incorrect behaviour or states relating to respiratory problems, restless leg syndrome, parasomnias, gastroesophageal reflux disease, etc.

Some individuals who suffer from hypersomnia, i.e. abnormal daytime drowsiness, complain that they are unable to fall asleep and only sleep for a few minutes, associated with agitation, which can become chronic with time.

Hypersomnia is not a common situation, whereas chronic insomnia is very frequent and alters the natural sleep cycle, which is difficult to restore, partly because sufferers try to sleep when they can during the day and then remain awake at night, thus disrupting the circadian rhythms. At this point, sleep deprivation can cause physical and mental problems which are so serious as to require corrective medicaments; however, like all drugs which act on the central nervous system, they are not free of major side effects.

The risks of long-term insomnia are cardiovascular, metabolic and immune deficiency-related.

Insomnia in its various forms is a problem which has been known since ancient times. In traditional medicine, numerous plants have been identified which, taken individually or in, even complex, mixtures, seem to improve the psychosomatic state. In fact, as in the case of all symptoms involving the nervous system, the placebo effect is significant. Extracts with psycho metabolic effects can also be used to regulate the appetite and body weight, with psychosomatic repercussions.

Products which are widely used orally are those derived from plants belonging to the Papaveraceae and Valerianaceae families, which have a hypnotic effect, or families of plants containing sedative flavonoids, such as passion flower, hawthorn, chamomile or plants rich in essential oils, such as Lavandula, Citrus and others.

The Valerianaceae are widely used although they do not have clinically supported activities, as in the case of many other commonly used plants.

Some essential oils administered orally at high doses, or as aromatherapy devised at the time of use, recently entered the pharmaceutical and nutraceutical formulary.

Shen et al. [Neuroscience Letters 383 (2005) 188-193] discloses the effect of lavender oil and its active component, linalool, administered by inhalation of a water suspension, on the autonomic nerves, and its ability to suppress lipolysis through a histaminergic response, and enhance appetite and body weight. This document does not disclose or suggest administering lavender oil or linalool in combination with carriers/vehicles other than water or with other active ingredients.

De Moura Linck et al. [Phytomedicine 16 (2009) 303-307] reports the results of a study carried out to evaluate the sedative effects of linalool (one of the active ingredients of lavender oil) in mice; in the study, linalool was administered by inhalation, diluted in Tween 80 (v/v).

WO 2008/155592 (INVENCIO-21 GYOGYHATASU KE SZITMEN YEKET GYARTOKFT), published on December 24, 2008, relates to liposome compositions containing essential oils and vitamins. In particular, this document discloses a liposome composition comprising a citrus essential oil and lavender oil of pharmaceutical grade, ethoxylated castor oil and a phospholipid. The compositions are prepared by mixing the essential oils, vitamins, ethoxylated castor oil and a phospholipid, followed by:

a) addition of water to obtain a liposomal hydrophilic phase, which is converted into a liposomal composition by addition of ethanol, or b) addition of ethanol to form a liposomal lipophilic phase, which is converted into a liposomal hydrophilic composition by addition of distilled water.

The compositions of WO 2008/155592 are said to be useful for the treatment of skin injuries.

US 2013/0039978 Al (HASANAGIC VEDRAN; SCHWARZ JOSEPH;

WEISSPAPIR MICHAEL), published on February 14, 2013, discloses compositions comprising essential oils, including lavender oil and bergamot oil, in the form of oil-in-water emulsions, for the treatment of infections of the urinary tract.

Fisk, I.D. et al. [Food Research International 54 (2013) 861-866] disclose particles obtained by spray-drying of an emulsion obtained from an oil, water, a carrier (oxylsuccinated starch or lecithin) and D-limonene. This document focuses on formulation issues of volatile lipophilic actives, and does not mention any medicinal or nutraceutical applications of the particles.

Nagai K. et al. [Autonomic Neuroscience: Basis and Clinical 185 (2014) 29-35] provide a review of the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. This document does not disclose or suggest administering the oils orally.

Navarra M. et al. [Frontiers in Pharmacology (2015) vol. 6, article 36], relate to Citrus bergamia (bergamot) oil, and mentions its ability to reduce stress responses, serum Cortisol levels, blood pressure, pain and depression. The same effects are disclosed for lavender oil. However, this document refers only to topical application and inhalation of the oils.

De Sousa D.P. et al. (Molecules 2015, 20, 18620-18660) provide a review of the anxiolytic- like effects of essential oils, including citrus oils and Lavandula angustifolia oil, in animal models. However, this document does not disclose or suggest specific administration forms, nor does it suggest any specific combination with carriers or vehicles.

FR 2762993 (Institut de Recherche Biologique Anonyme - FR), published on May 6, 1997, discloses the use of phospholipids of animal origin for the preparation of therapeutic or dietetic compositions for the regulation of melatonin secretion. Administration can be effected as solid or liquid dosage forms. This document does not disclose or suggest the combination with oils of vegetable origin.

Lee H.S. et al. [Life Sciences 118 (2014) 7-14] present the results of a study aimed at verifying the effects of soybean phosphatidylcholine (PC) on high-fat diet-induced obesity hyperlipidaemia and fatty liver in mice. PC was administered as a suspension in water.

WO 2017/009711 (ENZYMOTECH LTD.), published on January 19, 2017 discloses phospholipid compositions for the improvement of sleep; this document does not disclose or suggest combinations with essential oils, and refers to functional foods or discrete dosage units, powders, granules, solutions, suspensions, syrups or elixirs as administration forms.

An essential oil of lavender was recently introduced onto the market as an anxiolytic at a dose of 80 mg/unit in capsules, and its efficacy was compared with a well-known benzodiazepine (Woelk. Phytomedicine 2010, 12, 94-99; Kasper, European Neuropsycopharmacology, 2015, 25, 1960-67).

However, high doses of essential oils are not free of gastroenteric side effects, in view of the considerable antibacterial activity of those active ingredients and a fairly high irritant power, and can lead, for example, to gastroesophageal reflux.

In the long term, continuous oral use of large amounts of essential oils leads to problems of renal elimination, to the extent that the treatment has to be discontinued.

The classic aromatherapy treatment of anxiety and sleep disorders is known in traditional medicine, wherein its use is left to the user, who applies the oil to various parts of the body, such as the temples or feet, or sprinkles a few drops in boiling water and inhales the vapours. However, these uses are not standardisable, and in particular are not easy to apply; for these reasons, the approaches used in traditional medicine have not led to definite conclusions about their efficacy and use. Oral administrations at high doses were introduced to eliminate these drawbacks, but this involves the adverse effects described above.

There is consequently still a need to identify alternative products useful in the prevention and/or treatment of insomnia and anxiety, and in appetite reduction and metabolic stimulation.

Summary of the invention

The present invention relates to solid powdered compositions [compositions (C)] comprising at least one phospholipid [phospholipid (PL)] and at least one essential oil [essential oil (O)] deriving from citrus fruits or from Lavandula officinalis.

The invention also relates to the use of compositions (C) to prepare pharmaceutical or nutraceutical formulations [formulations (F)] which are useful in the prevention and/or treatment of insomnia and anxiety, in appetite reduction and metabolic stimulation, treatment of excess weight and obesity, and body weight reduction.

Detailed description of the invention

It has surprisingly been found that solid powdered compositions [compositions (C)] comprising at least one phospholipid [phospholipid (PL)] and at least one essential oil deriving from citrus fruits or Lavandula officinalis [essential oil (O)] are useful in the treatment of insomnia and anxiety, in appetite reduction and metabolic stimulation.

Typically, compositions (C) are in the form of powders in which the at least one essential oil (O) is homogeneously dispersed in the at least one phospholipid (PL). Preferably, compositions (C) also comprise at least one additional ingredient [ingredient (I)] that improves the physical and technological characteristics of compositions (C) and allows easier manufacturing of pharmaceutical or nutraceutical formulations [formulations (F)] for oral or topical administration.

Before disclosing the invention in detail, it is pointed out that each publication or patent document cited in the present application is incorporated by reference in its entirety. The citation of any such document is not to be interpreted as an admission that it is prior art with respect to the present invention. In case of discrepancy between the content of such publication or patent document and the present description, the latter shall prevail. Furthermore, for the avoidance of doubt, within the present application:

- when ranges are indicated, the lowest and highest extremes of the range are included;

- the expression "essential oil (O)" excludes hydroalcoholic extracts from citrus fruits or from Lavandula officinalis; the expression "at least one essential oil

(O)" means that compositions (C) can contain one single essential oil or mixtures of essential oils; alternatively, as explained in greater detail below, in compositions (C) the at least one essential oil (O) can be replaced by one or more pure active ingredients of said essential oils (O);

- the expression "at least one phospholipid (PL)" denotes one single phospholipid or a mixture of phospholipids obtained from one single vegetable or animal source, or a mixture of phospholipids obtained from different vegetable or animal sources.

The essential oils are preferably obtained from the fruit of Citrus bergamia, Citrus Union, Citrus paradisi and Lavandula ojficinalis. Said oils can be obtained traditionally by distillation in steam current, extraction with hypercritical gases or solvents, or pressing. The essential oil is preferably obtained from Citrus bergamia fruits.

Essential oil of Citrus bergamia can be prepared by pressing, and preferably contains 35% linalool, 30% linalyl acetate and 20% limonene, together with small amounts of other terpenes.

Essential oil of Citrus paradisi can be prepared by pressing and distillation.

Essential oil of Lavandula ojficinalis preferably contains linalool and linalyl acetate in about the same ratio, together with a small portion of other monoterpenes.

As mentioned hereinbefore, compositions (C) can contain, instead of essential oil (O), one or more pure active ingredients contained in said essential oils (O), such as linalool, linalyl acetate and limonene. For example, the compositions can comprise linalool, linalyl acetate and limonene, preferably in a weight ratio of 1 : 1 : 1.

According to a preferred aspect, a composition (C) comprises a single essential oil deriving from citrus fruits, preferably an essential oil of Citrus bergamia. According to another preferred aspect, a composition (C) only comprises essential oil of Lavandula officinalis.

The at least one phospholipid (PL) can be selected from the group comprising lecithins obtained from soy, sunflower or egg, phosphatidyl choline, phosphatidyl serine or phosphatidyl ethanolamine, wherein the acyl groups, being the same or different, are mostly derived from palmitic, stearic, oleic, linoleic, linolenic acids or combinations thereof. Preferably, the phospholipid (PL) is a lecithin; more preferably, the lecithin is soy lecithin or sunflower lecithin; even more preferably, the lecithin is sunflower lecithin.

The essential oil (0):phospholipid (PL) ratio ranges from 2: 1 to 1 : 10, preferably from 1 : 1 to 1 :5.

The at least one additional ingredient [ingredient (I)] contained in compositions (C) can be a surfactant other than a phospholipid [surfactant (S)] or a non- surfactant ingredient [non- surfactant (NS)]. Preferably, compositions (C) contain at least one surfactant (S) other than a phospholipid (PL) and at least one non- surfactant (NS).

Typically, surfactant (S) is a surfactant having an HLB value equal to or higher than 12. Surfactant (S) enhances incorporation and homogeneous dispersion of essential oil (O) in the manufacturing process of composition (C) and maximises the interaction of essential oil (O) with the selected phospholipid (PL). Furthermore, surfactant (S) enhances the wettability and fast dispersion of composition (C) in the gut fluids and promotes faster and higher absorption and, therefore, higher bioavailability of the active ingredient(s) of essential oil (O). Surfactant (S) is preferably selected from the group comprising sucrose esters, polysorbates, polyoxyethylene castor oil derivatives, polyoxy ethylene stearates, D-a-tocopheryl polyethylene glycol succinate and combinations thereof, sucrose esters being preferred.

Non- surfactant ingredient (NS) can be:

a soluble or insoluble filler [filler (F)], preferably selected from cellulose powder, microcrystalline cellulose, calcium carbonate, calcium phosphate, mannitol, cyclodextrins, typically maltodextrins, sorbitol, xylitol, fructose, isomalt, inulin and combinations thereof, and/or

another ingredient selected from one or more of methylcellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, natural gums, silicon dioxide, talc, stearic acid and magnesium stearate and combinations thereof.

Compositions (C) are typically prepared by a manufacturing method [method (M)] which comprises mixing at least one essential oil (O) with at least one phospholipid (PL) to obtain a homogeneous mixture, and optionally adding at least one additional ingredient (I), preferably at least one surfactant (S) and at least one non-surfactant (NS).

In a preferred embodiment, method (M) consists of the following steps:

a) mixing at least one essential oil (O) with at least one phospholipid (PL) to obtain an oil (0)/phospho lipid (PL) mixture [mixture (MX-1)];

b) mixing at least one surfactant (S) with at least one filler (F) to obtain a surfactant (S)/filler (F) mixture [mixture (MX-2)];

c) mixing mixtures (MX-1) and (MX-2) to obtain a composition (C).

In another preferred embodiment, method (M) consists of the following steps: mixing at least one essential oil (O) with at least one phospholipid (PL) to obtain an oil (0)/phospho lipid (PL) mixture [mixture (MX-1)];

adding at least one filler (F) to mixture (MX-1)] and mixing to obtain a composition (C).

Method (M) can be carried out by a person skilled in the art with conventional equipment; a person skilled in the art will be able to select additional ingredients (I) and mixing times according to the selected essential oil (O) and its final concentration in the target composition (C).

The ratio between the essential oils and the additional ingredients ranges between

1 : 1 and 1 :30, preferably between 1 :10 and 1 :30.

Compositions (C) are useful in the treatment of insomnia and anxiety, in appetite reduction and metabolic stimulation. Compositions (C), by reducing the appetite and/or stimulating the metabolism, are consequently useful in weight reduction in general, and may be used in the treatment of excess weight and obesity in particular.

The treatment may be given one to three times a day, administering the composition orally or sublingually or in retro auricular patches at doses to be established on the basis of the patient's body weight.

Compositions (C) were tested on a preliminary basis on rats, monitoring the electroencephalogram before and during the treatment and placing the laboratory animal in a controlled atmosphere of active ingredient, as reported in the literature to evaluate its efficacy in aromatherapy.

It was surprisingly found that compositions (C) according to the invention give rise to a drastic reduction in the amount of essential oil (O) to be administered, therapeutic effect being equal, thus eliminating the side effects associated with the use of essential oils. Moreover, the effect obtainable by treatment with compositions (C) is immediate, and produces a rapid response. Compositions (C) unpredictably exhibit an early plasma peak of the active ingredients.

Compositions (C) are particularly useful in paediatrics, as the waking/sleep problem is particularly significant in growing children.

Essential oils are also characterised by an analgesic activity which can be useful in states of anxiety and insomnia, especially when associated with chronic pain in the elderly and in long-term oncological patients, before moving on to appropriate painkilling treatments. The target of the active ingredients is mainly the limbic system of the hypothalamus, from which biochemical and neuronal messages are transmitted to specific sites. The hypothalamic-pituitary-adrenal axis is involved in metabolic regulation as well as insomnia.

Accordingly, a further object of the present invention is the use of compositions (C) for the manufacture of formulations for pharmaceutical or nutraceutical use [formulations (F)]. A still further embodiment of the invention is a method [method (Ml)] for treating insomnia and anxiety, for reducing appetite and/or for stimulation of metabolism, said method comprising administering a composition (C) or a formulation (F) to a subject in need thereof.

Formulations (F) can be designed for oral or topical administration. Non-limiting examples of formulations (F) for oral administration include tablets, capsules and dispersible granules, optionally for sublingual administration, while non-limiting examples of topical formulations (F) are gels and patches, preferably patches, more preferably patches to be applied to the retroauricular skin. Formulations (F) can be prepared by a person skilled in the art according to conventional techniques, such as those described in Remington's Pharmaceutical Handbook, Mack Publishing Co., N.Y., USA.

When required, one or more excipients of nutraceutical grade may be added to compositions (C) for the manufacture of formulations (F).

In formulations (F), the amount of the at least one essential oil (O) may range from 2 to 20% w/w, and preferably ranges from 2 to 10% w/w of the total weight of the formulation.

The amount of essential oil (O) per dose when administered orally may vary from 5 to 20 mg, and preferably amounts to 10 mg; when administered by the sublingual and/or retroauricular route it may range from 2 to 10 mg, and preferably amounts to 3 mg.

Essential oil of Citrus bergamia (bergamot orange) may be incorporated in compositions for oral use as described in the examples, or in crosslinked hyaluronic acid or collagen for sublingual treatment. Essential oil of Citrus bergamia may be administered in daily doses ranging from 5 to 25 mg, preferably 10 mg.

Essential oil of Citrus paradisi (grapefruit) may be administered in daily doses ranging from 5 to 25 mg, preferably 10 mg.

The examples below further illustrate the invention. Example 1

Composition (C) containing essential oil of Citrus bergamia

Composition

Essential oil of Citrus bergamia 3.3%

Liquid sunflower lecithin 10.0%

Sucrose monopalmitate 33.3%

Microcrystalline cellulose 50.7%

Silicon dioxide 2.7%

Manufacturing process

Mix liquid sunflower lecithin and essential oil of Citrus bergamia. Mix sucrose monopalmitate and microcrystalline cellulose. Allow the Citrus bergamia essential oil/sunflower lecithin mixture to adsorb on the sucrose monopalmitate/microcrystalline cellulose mixture. Mix the resulting product with silicon dioxide.

Example 2

Composition (C) containing essential oil of Lavandula officinalis

Composition

Essential oil of Lavandula officinalis 5.6%

Sunflower lecithin 22.2%

Calcium carbonate 71.4%

Silicon dioxide 0.8%

Manufacturing process

Allow the essential oil of Lavandula officinalis to adsorb on sunflower lecithin, mixing at length to promote the interaction. Add calcium carbonate and silicon dioxide to the mixture and mix for 10 minutes. Example 3 - Formulation (F) - Tablets

Tablets containing 300 mg of the composition of Example 1 were prepared.

Composition per dosage unit

Composition of Example 1 300.0 mg

(equal to essential oil of Citrus bergamia 10.0 mg)

Microcrystalline cellulose 180.0 mg

Crosslinked sodium carboxymethylcellulose 12.0 mg

Silicon dioxide 4.0 mg

Magnesium stearate 4.0 mg

Manufacturing process

Mix the composition of example 1 with microcrystalline cellulose and crosslinked sodium carboxymethylcellulose for about 10 minutes.

The resulting product is calibrated on a 40-mesh screen and mixed for a further 5 minutes with silicon dioxide and magnesium stearate.

The resulting mixture is compressed with a rotary tablet press equipped with rounded convex punches having a diameter of 11 mm.

Example 4 - Hard gelatin capsules

Hard gelatin capsules were prepared containing 180 mg of the composition of Example 2, corresponding to 10 mg of essential oil of Lavandula officinalis.

Composition

Solid dispersion (Example 2) 180.0 mg

(equal to essential oil of Lavandula officinalis 10.0 mg

Silicon dioxide 2.0 mg

Manufacturing process

Mix the solid dispersion described in Example 2 with silicon dioxide for 5 minutes. Divide the resulting powder between hard gelatin capsules, format 2, at the rate of 182 mg/capsule. Example 5 - Efficacy test

The efficacy of the compositions according to the invention in clinical pharmacology was evaluated by examining parameters relating to induced anxiety, depression and mood parameters, evaluating the amount of circulating Cortisol measured in the saliva by a known clinical procedure.

In the modulation of anxiety-related insomnia, 60 patients with a mean age of 40 years, suffering from insomnia as a result of anxiety states of various origins, were treated. The patients randomised with a comparable neurovegetative profile were treated with a placebo (formulation without essential oil) or with the composition of example 3, administered one hour before going to bed. The treatment was repeated every day for 4 weeks.

In the morning, the patient was asked to fill in a questionnaire reporting on the speed of falling asleep, any calming effect following the treatment, sleep quality, and in the event of nocturnal threshold consciousness, its frequency. The evaluation criterion used was the Leeds Sleep Evaluation Questionnaire (SEQ), a tool designed to evaluate the effects of psychoactive drugs on sleep, which consists of a self-assessment with a visual analogue technique.

The SEQ explores 10 aspects of sleep, including the following four:

Getting to sleep (GTS)

Quality of sleep (QOS)

Awakening from sleep (AFS)

Behaviour following wakefulness (BFW)

Treatment with the composition of example 3 produced a mediated global difference of 39% compared with the placebo, and a difference of 71±18% compared with the baseline.

According to the statistical analysis, the efficacy was much higher for the composition of example 1 than the placebo. Example 6 - Efficacy test

In the case of appetite modulation and metabolic stimulation, the procedure described below was followed.

The patients were treated with a hard gelatin capsule, prepared according to example 4, half an hour before the two main meals, and reported in a questionnaire on their sensations of hunger/satiety, state of health, changes in diuresis since the baseline, effect on mood, and on the state of anxiety in general.

The satiety evaluation was conducted with the Haber test.

For appetite control in overweight patients with a BMI>30 following a forced low-calorie diet, Citrus paradisi essential oil was administered, and the patients were monitored with the Haber scale.

Clinically, the composition of example 2 was administered to 42 patients, mainly women, in a double-blind trial; after randomisation, the patients were treated with the placebo or with the composition of example 2 for 60 days, 10 minutes before the main meals.

For the efficacy evaluation in terms of satiety and consequently of appetite, the Haber scale was used, which has appetite as primary endpoint and psychosomatic parameters as secondary endpoints. The Haber scale is a visual scale scored from -10 to +10, wherein -10 represents maximum hunger and +10 represents maximum satiety.

The patient was asked to indicate their sensation of hunger before the midday meal.

To ensure optimum identification of each change of satiety according to the Haber scale, the monitoring times were established equally for both groups, treated with the composition of example 2 and the placebo respectively, and the non-parametric Friedman test was used for the statistical evaluation, evaluating the sensation of satiety between the baseline and the six periods of time established for each group.

The average in the Haber test was significantly higher in the group treated with the composition of example 2 (Friedman's test 41.49 p < 0.0001), shifting from negative to positive values. Specifically, the scores expressed for the sensation of satiety were considerably different from the baseline scores on each subsequent check.

Conversely, the placebo group (Friedman's test 9.62 p= 0.14) exhibited a weak but not significant initial increase.

The composition of example 2 is therefore much more effective than the placebo. Appetite reduction and body metabolism stimulation using a composition of example 2 according to the invention was reflected by a reduction in body weight.

Claims

I . Solid powdered compositions comprising at least one phospholipid and at least one essential oil deriving from citrus fruits or Lavandula officinalis.

2. Compositions as claimed in claim 1, wherein the at least one essential oil deriving from citrus fruit is obtained from the fruit of Citrus bergamia, Citrus Union or Citrus paradisi.

3. Compositions as claimed in claim 2, only comprising essential oil obtained from Citrus bergamia.

4. Compositions as claimed in claim 2, only comprising essential oil of Lavandula ojficinalis.

5. Compositions as claimed in any one of claims 1 to 3, wherein the essential oil is replaced by one or more of the active ingredients contained in the essential oil, which are selected from linalool, linalyl acetate and/or limonene.

6. Compositions as claimed in any one of claims 1 to 5, wherein the at least one phospholipid is selected from the group comprising lecithins obtained from soy, sunflower or egg, phosphatidyl choline, phosphatidyl serine or phosphatidyl ethanolamine, wherein the acyl groups, being the same or different, are mostly derived from palmitic, stearic, oleic, linoleic, linolenic acids or combinations thereof.

7. Compositions as claimed in any one of claims 1 to 6, wherein the ratio between essential oils and phospholipids ranges between 2: 1 and 1 : 10.

8. Compositions as claimed in any one of claims 1 to 7, further comprising at least one ingredient selected from surfactants other than a phospholipid, or a non-surfactant ingredient.

9. Compositions as claimed in claim 8, wherein the ratio between the essential oils and the additional ingredients ranges between 1 : 1 and 1 :30.

10. Pharmaceutical or nutraceutical formulations for oral or retroauricular administration containing a composition as claimed in any one of claims 1 to 9.

I I . Compositions as claimed in any one of claims 1-10, for use in the treatment of insomnia or anxiety, or in appetite reduction or metabolic stimulation.