COMPOSITIONS COMPRISING ESSENTIAL OILS FOR TOPICAL USE

Abstract

Disclosed are compositions including one or more essential oils selected from oils deriving from citrus fruits, Lavandula officinalis or Cinnamomum cassia. The compositions may preferably be administered topically. The compositions are useful in the prevention and/or treatment of insomnia and anxiety, and in reducing appetite and stimulating the metabolism.

Claims

1. Compositions comprising one or more essential oils deriving from citrus fruits, Lavandula officinalis or Cinnamomum cassia.

2. Compositions according to claim 1, comprising an essential oil of Citrus bergamia in combination with an essential oil of Lavandula officinalis.

3. Compositions according to claim 2, wherein the essential oil of Citrus bergamia and the essential oil of Lavandula officinalis are in a weight ratio of 10:1.

4. Compositions according to claim 1, comprising an essential oil of Citrus paradisi and an essential oil of Cinnamomum cassia.

5. Compositions according to claim 1, wherein the essential oil is replaced with one or more active ingredients contained in the essential oil selected from linalool, linalyl acetate and/or limonene.

6. Compositions according to claim 1, wherein said compositions are administered by the topical route.

7. Compositions according to claim 6, wherein the compositions are applied in the nasal and/or perinasal and/or labial area.

8. A method for treatment of insomnia, comprising administering an effective amount of the composition of claim 1.

9. A method for treatment of anxiety, comprising administering an effective amount of the composition of claim 1.

10. A method for reduction of appetite and/or in the stimulation of the metabolism, comprising administering an effective amount of the composition of claim 1.

11. A method for treatment of excess weight and obesity, comprising administering an effective amount of the composition of claim 1.

12. (canceled).

13. Compositions according to claim 2, wherein the essential oil is replaced with one or more active ingredients contained in the essential oil selected from linalool, linalyl acetate and/or limonene.

14. Compositions according to claim 3, wherein the essential oil is replaced with one or more active ingredients contained in the essential oil selected from linalool, linalyl acetate and/or limonene.

15. Compositions according to claim 4, wherein the essential oil is replaced with one or more active ingredients contained in the essential oil selected from linalool, linalyl acetate and/or limonene.

16. Compositions according to claim 2, wherein said compositions are administered by the topical route.

17. Compositions according to claim 3, wherein said compositions are administered by the topical route.

18. Compositions according to claim 4, wherein said compositions are administered by the topical route.

19. Compositions according to claim 5, wherein said compositions are administered by the topical route.

20. A method of treating insomnia, comprising administering an effective amount of the composition according to claim 2.

21. A method of treating insomnia, comprising administering an effective amount of the composition according to claim 3.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0039] It has surprisingly been found that compositions comprising one or more essential oils selected from oils deriving from citrus fruits, Lavandula officinalis or Cinnamomum cassia are useful in the treatment of insomnia and anxiety, appetite reduction and metabolic stimulation.

[0040] The essential oils are preferably obtained from the fruit of Citrus bergamia, Citrus limon, Citrus paradisi and Lavandula officinalis. Said oils may be obtained traditionally by steam current distillation or extraction with hypercritical gases. The essential oil is preferably obtained from Citrus bergamia.

[0041] 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.

[0042] Essential oil of Citrus paradisi may be prepared by pressing and distillation.

[0043] Essential oil of Lavandula officinalis preferably contains linalool and linalyl acetate in about the same ratio, together with a small portion of other monoterpenes.

[0044] Said compositions can contain a single essential oil or mixtures of said essential oils.

[0045] Alternatively, the compositions may comprise the active ingredients contained in said essential oils, 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.

[0046] According to a preferred aspect, the compositions comprise as essential oil only an essential oil of Citrus bergamia.

[0047] According to another preferred aspect, the compositions comprise an essential oil of Citrus bergamia combined with essential oil of Lavandula officinalis, preferably in a weight ratio of 10:1.

[0048] According to a further preferred aspect, the compositions comprise as essential oil only an essential oil of Citrus paradisi.

[0049] According to a still further preferred aspect, the compositions comprise an essential oil of Citrus paradisi and an essential oil of Cinnamomum cassia.

[0050] In another further preferred aspect, the compositions comprise an essential oil deriving from citrus fruit, an essential oil of Lavandula officinalis and an essential oil of Cinnamomum cassia.

[0051] In the compositions according to the invention, the one or more essential oil , may range from 2% to 25% w/w, and preferably amounts to 15% or 20% w/w with respect to the overall weight of the composition.

[0052] In compositions wherein Citrus bergamia essential oil is the sole essential oil, its amount may range from 5% to 25% w/w, and preferably amounts to 10% or 15% w/w.

[0053] In compositions wherein Citrus paradisi (grapefruit) essential oil the sole essential oil, its amount may range from 10% to 25% w/w, and preferably amounts to 18% or 20% w/w.

[0054] The compositions according to the invention may be administered one to three times a day, preferably applying 10-50 mg of composition in the nasal and perinasal area.

[0055] According to a further aspect, the compositions may be administered topically, for example nasally, perinasally, labially, or in other suitable parts of body.

[0056] The compositions may be incorporated in semisolid formulations, such as ointments, gels or creams. Such formulations include, in addition to the one or more aforementioned essential oils, other ingredients or excipients suitable to dilute the oil(s) to a desired concentration and to allow topical application. Such other ingredients include vegetable oils and/or fats like, for example, Ricinus communis seed oil, avocado oil, Prunus amygdalus dulcis oil, shea butter; thickening agents; surfactants and antioxidants.

[0057] The compositions according to the invention may be formulated according to conventional techniques, such as those described in Remington's Pharmaceutical Handbook, Mack Publishing Co., N.Y., USA.

[0058] The compositions according to the invention are useful in the treatment of insomnia and anxiety, appetite reduction and metabolic stimulation.

[0059] The compositions according to the invention, reducing appetite and/or stimulating metabolism, are consequently useful in weight reduction in general and, in particular, may be used in the treatment of excess weight and obesity.

[0060] It has surprisingly been found that the compositions according to the invention, administered topically in the labial, perinasal and nasal areas, induce sleep in individuals suffering from insomnia, which is often anxiety-dependent, in a short time and a comfortable way, without any side effects in view of the small amount of essential oils administered.

[0061] Moreover, the compositions are characterised by ease of use, even during the night when the patient wakes up and has difficulty getting back to sleep again.

[0062] The compositions according to the present invention are particularly useful in paediatrics, as the waking/sleep problem is particularly significant in growing children.

[0063] 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.

[0064] The combinations to be administered to humans were tested on a preliminary basis on rats, monitoring the electroencephalogram before and during the treatment and placing the laboratory animals in a controlled atmosphere of active ingredient, as reported in the literature to evaluate its efficacy in aromatherapy.

[0065] Accordingly, the present invention further relates to a method for treating insomnia and anxiety, in particular anxiety-related insomnia, said method comprising administering to a subject in need thereof an effective amount of a composition, preferably in the form of an ointment, gel or cream, said composition comprising one or more essential oils selected from oils deriving from citrus fruits, Lavandula officinalis or Cinnamomum cassia.

[0066] In a preferred aspect, the method is a method for treating anxiety-related insomnia, said method comprising administering to a subject in need thereof an effective amount of a composition comprising as essential oil only an essential oil of Citrus bergamia. Preferably, the composition comprises also Ricinus communis seed oil, avocado oil and Prunus amygdalus dulcis oil.

[0067] The present invention also relates to a method for reducing appetite and stimulating metabolism, for the treatment of excess weight and obesity and for body weight reduction said method comprising administering to a subject in need thereof an effective amount of a composition, preferably in the form of an ointment, gel or cream, said composition comprising one or more essential oils selected from oils deriving from citrus fruits, Lavandula officinalis or Cinnamomum cassia.

[0068] In a preferred aspect, the method is a method for reducing appetite, stimulating metabolism and reducing body weight, said method comprising administering to a subject in need thereof an effective amount of a composition comprising as essential oil only an essential oil of Citrus paradisi. Preferably, the composition further comprises also Ricinus communis seed oil, avocado oil and Prunus amygdalus dulcis oil.

[0069] The examples below further illustrate the invention.

Example 1-Formulation as a Perinasal Ointment Based on Essential Oil of Citrus bergamia

[0070] A composition was prepared comprising (% w/w):

TABLE-US-00001 Essential oil of Citrus bergamia 15% Ricinus communis seed oil 20% Avocado oil 25% Prunus amygdalus dulcis oil 15% Dermofeel Viscolid 5% Dermofeel Sensolv 10% Shea butter 9.5% Aperoxid TLA 0.5%

Example 2

[0071] A composition was prepared comprising (% w/w):

TABLE-US-00002 Essential oil of Citrus bergamia 10% Essential oil of Lavandula officinalis 5% Ricinus communis seed oil 20% Avocado oil 25% Prunus amygdalus dulcis oil 15% Dermofeel Viscolid 5% Dermofeel Sensolv 10% Shea butter 9.5% Aperoxid TLA 0.5%

Example 3

[0072] A composition was prepared comprising (% w/w):

TABLE-US-00003 Essential oil of Citrus paradisi 20% Ricinus communis seed oil 20% Avocado oil 25% Prunus amygdalus dulcis oil 10% Dermofeel Viscolid 5% Dermofeel Sensolv 10% Shea butter 10%

Example 4

[0073] A composition was prepared comprising (% w/w):

TABLE-US-00004 Essential oil of Citrus paradisi 18% Essential oil of Cinnamomum cassia 2% Ricinus communis seed oil 20% Avocado oil 25% Prunus amygdalus dulcis oil 10% Dermofeel Viscolid 5% Dermofeel Sensolv 10% Shea butter 10%

Example 5

[0074] A composition was prepared comprising (% w/w):

TABLE-US-00005 Linalool 6% Linalyl acetate 8% Limonene 6% Ricinus communis seed oil 20% Avocado oil 25% Prunus amygdalus dulcis oil 10% Dermofeel Viscolid 5% Dermofeel Sensolv 10% Shea butter 10%

Example 6-Efficacy Test

[0075] The efficacy of the compositions according to the invention in clinical pharmacology was evaluated by examining parameters relating to induced anxiety, depression and humoral mood parameters, evaluating the amount of circulating cortisol measured in the saliva by a known clinical procedure.

[0076] In the modulation of anxiety-related insomnia, 36 female patients 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 formulation of example 1, administered in the labial, perinasal or proximal nasal area for 2 weeks. They were required to take the formulation before going to bed, preferably always at the same time. In the morning, each 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:

[0077] Getting to sleep (GTS),

[0078] Quality of sleep (QOS),

[0079] Awakening from sleep (AFS),

[0080] Behaviour following wakefulness (BFW).

[0081] Treatment with the formulation of example 1 produced a mediated global difference of 35% compared with the placebo, and a difference of 7221% compared with the baseline value.

[0082] According to the statistical analysis, the efficacy was much higher for the composition of example 1 than the placebo. Example 7-Efficacy Test

[0083] In the case of appetite modulation and metabolic stimulation, the procedure described below was followed.

[0084] The patients were treated during the day with the same amount of formulation taken 3 times a day at mealtimes (breakfast, lunch and dinner). The cortisol content of the saliva was evaluated 15 min. after administration to provide biochemical evidence of the ingestion of the product.

[0085] For appetite control in overweight patients with a BMI>30 following a forced low-calorie diet, Citrus paradisi oil was administered, and the patients were monitored with the Haber scale.

[0086] Clinically, the formulation of example 3 was administered to 42 patients, mainly women, in a double-blind trial; after randomisation the patients were divided into two groups and treated with the placebo or the formulation of example 3 for 60 days, applying the formulation perinasally 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.

[0087] To ensure optimum identification of each change of satiety according to the Haber scale, the monitoring times were established equally for both groups, 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 formulation of example 3 (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.

[0088] The formulation of example 3 is therefore clearly superior to the placebo in terms of efficacy. Appetite reduction and body metabolism stimulation using a composition of example 3 was reflected by a reduction in body weight.