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WO2019030209A1 - Composition d'huile essentielle de katrafay et son utilisation comme produit cosmétique, médicament et/ou complément nutritionnel - Google Patents

Composition d'huile essentielle de katrafay et son utilisation comme produit cosmétique, médicament et/ou complément nutritionnel Download PDF

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Publication number
WO2019030209A1
WO2019030209A1 PCT/EP2018/071353 EP2018071353W WO2019030209A1 WO 2019030209 A1 WO2019030209 A1 WO 2019030209A1 EP 2018071353 W EP2018071353 W EP 2018071353W WO 2019030209 A1 WO2019030209 A1 WO 2019030209A1
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Prior art keywords
composition
ishwarane
limonene
katrafay
essential oil
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Ceased
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Inventor
Luisa Pecorari
Tatiana VIGNUDELLI
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Ophera Srl
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Ophera Srl
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/31—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin

Definitions

  • the present invention relates to a composition based on katrafay essential oil (Cedrelopsis grevei) and formulations containing said composition, particularly for use in the treatment of inflammation states.
  • katrafay essential oil Cedrelopsis grevei
  • Extracts and essential oils of vegetable origin have long been used for therapeutic purposes or to prevent the occurrence of various types of conditions.
  • the katrafay essential oil (Cedrelopsis grevei), an aromatic plant native to Madagascar, is extracted from the bark and leaves and is widely used in folk medicine.
  • the katrafay essential oil (hereafter referred to as "katrafay oil”) has been shown to have antioxidant, cytotoxic (has been effective against the MCF-7 tumor cell line), antimalarial (is active against Plasmodium falciparum, one of the species that causes malaria in humans) and, above all, antimicrobial and anti-inflammatory (demonstrated in an in vitro test based on the measurement of the inhibition of 5- lipoxygenase activity, from which an IC50 value of 21,33 mg/1).
  • Patent application JP 2005213202 A discloses the preparation of an antiinflammatory, anti-aging, antioxidant agent which can be used for cosmetic preparations and which contains Cedrelopsis grevei extract.
  • WO 2008034821 Al discloses the use of active ingredients extracted from various plant species, including Cedrelopsis grevei, for the formulation of cosmetic or pharmaceutical preparations intended to protect the skin from dehydration and to relieve skin from chapping, stings, itching.
  • terpenes biomolecules consisting of multiples of the isoprenic unit, obtained in biological systems by the reaction of several units of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).
  • IPP isopentenyl pyrophosphate
  • DMAPP dimethylallyl pyrophosphate
  • the katrafay essential oil contains various terpenes, from which the antimicrobial and anti-inflammatory action depend and associated with the oil itself.
  • the main terpenes contained in the katrafay essential oil belong to the subclass of monoterpenes (e.g. limonene, alpha-pinene, beta-pinene) or to the subclass of sesquiterpenes (e.g. ishwarane, beta-elemene, alpha-copaene).
  • the terpenes have the ability to add ozone to the double bonds of isoprenic units (ozonation reaction), forming the corresponding ozonides.
  • Ozonides derived from terpenes (or ozonized terpenes) remain stable for long periods in an anhydrous environment and free from reducing agents, although they have the ability to act as fat-soluble oxidants and to release free oxygen.
  • the unsaturated triglycerides may go towards the ozonation reaction at the level of double bonds, forming ozonized derivatives having antimicrobial and anti-inflammatory action.
  • the ozonized terpenes have two advantages compared to the unsaturated ozonized triglycerides.
  • the ozonized terpenes have a significantly lower molecular weight (about 1/5 or 1/6 of the unsaturated ozonized triglycerides), a feature that gives them a much higher capacity to spread through biological tissues and an affinity towards water considerably more high, which results in greater reactivity in biological matrices.
  • the ozonized terpenes have a higher specific content of active oxygen with respect to unsaturated ozonized triglycerides, i.e. a greater content of active oxygen per mole of substance.
  • ozonized terpenes offer the advantage of not presenting the toxicity characterizing many of the respective terpenes.
  • the ozonized terpenes therefore have antimicrobial, antiviral, anti-inflammatory, and vulnerary (cicatrizant) activities and their use is known in the form of essential oils containing thereof or other formulations optimized according to application type, for the treatment of diseases such as: infections of various types, wounds, bedsores, arthritic pains, rheumatism, muscle injuries resulting from sports activities, dermatitis, psoriasis, gastroduodenal ulcer, etc..
  • Ishwarane is a sesquiterpenes in various plant species (including Cedrelopsis grevei, Bixa orellana, Aristolochia indica). Currently it is not known that ishwarane which is isolated from the extract has anti-inflammatory properties.
  • Limonene is a monoterpene that takes its name from the lemon tree ⁇ Citrus limon), but it is also in other plant species. Limonene exists naturally in two enantiomeric forms: lemon peel mainly contains L-limonene, while orange peel contains predominantly D-limonene. D-limonene is also present in many other botanical species, such as dill oil (Anethum graveolens) and cumin oil (Carum carvi), of which it is more than 30%; cumin oil also contains 48-65% of the oxygenated derivative of D-limonene ((+) - carvone), which has shown antitumor properties. D-limonene and carvone have also shown to exert significant anti-inflammatory effects.
  • D-limonene has neutralizing effects on gastric acids and is able to support normal peristalsis, characteristics that justify its use against gastroesophageal reflux disease. Furthermore, it has been described that D-limonene has chemopreventive properties for many types of tumors, particularly for breast, prostate, colon and skin cancer.
  • D-limonene is known for its high penetration capacity, particularly appreciable at the skin level, which is the reason why it is referred to as an "enhancer", to support the action of other molecules that alone would have little ability to cross epithelial barriers.
  • TNFa Tumor Necrosis Factor a
  • IL-6 Interleukin-6
  • D-limonene has shown to have intrinsic epithelial tissue repair properties, as its perillyl acid metabolite (POH) appears to be the key molecule in restoring homeostasis and skin integrity. In addition to its anti-inflammatory properties, D-limonene has remarkable properties to oppose to aging and promote skin rejuvenation.
  • POH perillyl acid metabolite
  • the main source of D-limonene is the oil obtained from citrus peel by cold pressing, which avoids the thermal degradation of components, unlike the process of hydrodistillation generally used to obtain essential oils.
  • limonene In Europe the use of limonene in cosmetic products is allowed, but being classified as an allergenic substance, its presence must be indicated in the list of ingredients, if it exceeds a certain level (0,001% for products intended to remain on the skin, as creams, ointments, deodorants, and 0,01% in products intended to be rinsed away from the skin, such as soaps or shampoos).
  • a certain level 0,001% for products intended to remain on the skin, as creams, ointments, deodorants, and 0,01% in products intended to be rinsed away from the skin, such as soaps or shampoos.
  • the non-oxidized D-limonene is inert and well tolerated; contact dermatitis can occur instead against oxidized D- limonene, which may be allergenic and irritating.
  • the term limonene refers indifferently to D- limonene, L-limonene or to a mixture of D-limonene and L-limonene
  • the primary task of the present invention is therefore to develop a composition based on katrafay essential oil (as well as a formulation which includes this oil) having superior anti-inflammatory efficacy with respect to the known compositions based on this essential oil.
  • an object of the invention is to provide a composition based on katrafay essential oil with high anti-inflammatory activity which is easy to administer, safe and non-toxic for the final consumer.
  • Another object of the invention is to provide a composition based on katrafay essential oil, the preparation of which is simple to make.
  • the present invention relates to a composition based on katrafay essential oil (Cedrelopsis grevei) comprising from 20% to 40% by weight with respect to the total weight of the ishwarane composition.
  • katrafay essential oil Cedrelopsis grevei
  • composition can optionally also include limonene, in such amount that the ratio in weight ishwarane: limonene is between 50: 1 and 100: 1.
  • the invention also relates to a formulation which includes the composition as described above.
  • Part of the invention is also a process for preparing the composition as well as its use as a cosmetic, as a medicine, or as a nutraceutical supplement, in particular for the treatment of inflammation states.
  • FIG. 1 shows a graph showing the effect of compositions comprising katrafay essential oil and various concentrations of ishwarane (0%, 5%, 10%, 20%>, 30%>, 40%, 50%, 60%) on expression of the inflammatory cytokine TNFa by cells of the THP-1 cell line, at basal conditions.
  • OEK katrafay essential oil
  • Ishw ishwarane
  • pure ishw composition comprising 100% ishwarane
  • Tnfa TNFa
  • C- negative control (untreated cells).
  • FIG. 2 shows a graph showing the effect of compositions comprising katrafay essential oil and various concentrations of ishwarane (0%>, 5%, 10%>, 20%>, 30%>, 40%, 50%, 60%) on expression of the inflammatory cytokine TNFa by cells of the THP-1 cell line, subjected to pre-stimulation with lipopolysaccharide (LPS).
  • OEK katrafay essential oil
  • Ishw ishwarane
  • pure ishw composition comprising 100% ishwarane
  • Tnfa TNFa
  • C- negative control (untreated cells, neither with OEK, nor with LPS);
  • C + positive control (cells treated only with LPS).
  • FIG. 3 shows a graph showing the effect of compositions comprising ishwarane and limonene in various weight ratios on the expression of the inflammatory cytokine TNFa by cells of the THP-1 cell line, subjected to pre-stimulation with lipopolysaccharide (LPS).
  • Column 3 (Ishw) shows the data related to cells treated with only 0,002% ishwarane.
  • C- negative control (untreated cells, neither with OEK, nor with LPS);
  • C + positive control (cells treated only with LPS).
  • FIG. 4 shows a graph showing the effect of compositions comprising katrafay essential oil and various concentrations of ishwarane (0%>, 5%, 10%>, 20%>, 30%>, 40%, 50%) on the expression of inflammatory cytokine TNFa by cells of the THP-1 cell line, subjected to pre-stimulation with lipopolysaccharide (LPS).
  • OEK katrafay essential oil
  • Ishw ishwarane
  • pure ishw composition comprising 100% ishwarane
  • Tnfa TNFa
  • C- negative control (untreated cells, neither with OEK, nor with LPS);
  • C + positive control (cells treated only with LPS).
  • the composition according to the present invention comprises katrafay essential oil (Cedrelopsis grevei) and is characterized by a content of ishwarane (which may be naturally present in the katrafay essential oil or added thereto) ranging between 20% and 40% by weight with respect to the total weight of the composition.
  • the katrafay essential oil is known for its anti-inflammatory and lenitive properties, above all, but not exclusively, in the skin and mucous membranes.
  • the inventors have surprisingly found that the presence of ishwarane terpene in the range of 20-40% by weight is able to enhance the anti-inflammatory and lenitive effect normally associated with the essential oil of katrafay.
  • the anti-inflammatory and lenitive effect is synergistically enhanced, i.e. this effect is greater than the sum of the effect that would be obtained by administering both components individually.
  • the composition of the invention can comprise from 25% to 35% of ishwarane by weight with respect to the total composition weight.
  • the composition may further comprises also the limonene terpene: the weight ratio between ishwarane and limonene must be between 50: 1 and 100: 1.
  • the limonene can be naturally present in the katrafay essential oil or added to it.
  • the anti-inflammatory and lenitive effect of synergistic type is manifested by inhibiting the biological response to pro-inflammatory stimuli, for example with the inhibition of the production of inflammatory mediators, typically cytokines and in particular interleukins and TNF (Tumor Necrosis Factor).
  • inflammatory mediators typically cytokines and in particular interleukins and TNF (Tumor Necrosis Factor).
  • composition of katrafay oil is closely related to its anti-inflammatory, lenitive, moisturizing properties.
  • In vitro experimental studies conducted by the inventors of the present patent application have made it possible to highlight how the content of some components (in particular, in fact, ishwarane and limonene) is decisive in terms of effectiveness.
  • the synergistic action in terms of anti-inflammatory and lenitive effect is closely correlated to the proportions between the components.
  • the synergistic action is achieved only when the content of ishwarane in the composition is between 20% and 40% by weight with respect to the total weight of the composition; if limonene is also present in the composition, a further synergistic effect is observed when the ratio in weight ishwarane: limonene is between 50: 1 and 100: 1. Outside the indicated ranges, the anti-inflammatory and lenitive effect of katrafay oil due to the presence of ishwarane (and possibly limonene) is not significantly enhanced.
  • LPS lipopolysaccharide
  • the THP-1 cell line is an immortalized line of human monocytes derived from a patient with acute monocytic leukemia; this cell line represents an experimental model for the in vitro study of the inflammation, which is accepted and commonly used by the scientific community.
  • Lipopolysaccharide is a component of the cell wall of Gram-negative bacteria; it is a macromolecule consisting of a lipidic portion and a polysaccharide portion capable of causing strong immune responses in animals, including humans.
  • the stimulation of a cell culture with lipopolysaccharide therefore, induces the inflammatory response and the consequent production of the inflammatory cytokine TNFa by monocytes, similarly to what happens in vivo in the presence of an inflammatory stimulus.
  • the THP-1 cells were pre-stimulated (or not) with LPS and treated (or not treated) with the composition of the invention to evaluate their ability to inhibit the inflammatory response by verifying the production of TNFa, as shown in examples.
  • composition according to the invention based on katrafay essential oil and comprising ishwarane in concentrations ranging from 20% to 40%, is able to reduce the production of TNFa by THP-1 cells in a more marked way (as a result of the synergistic effect) with respect to the reduction obtained by treating the same cells, under the same experimental conditions, with only katrafay oil or with compositions based on katrafay oil comprising concentrations of ishwarane outside the abovementioned concentration range.
  • katrafay essential oil may naturally contain a certain amount of ishwarane and limonene; katrafay oil is commonly marketed without titration in ishwarane and limonene, since the concentration of these active substances is subjected to natural variability depending on the plant part from which the oil is extracted, from the harvesting season, from the geographical plant origin and from its growth climate, as well as from the extraction method of the essential oil.
  • composition of the invention may therefore be necessary to add to the katrafay essential oil further ishwarane (previously purified) in addition to that naturally present in the oil itself.
  • ishwarane previously purified
  • this component it is possible that even a further amount of this component should be added to the katrafay essential oil.
  • the ishwarane added to the katrafay essential oil may be of natural origin, and preferably may be isolated from botanical species; in another embodiment, ishwarane may be of synthetic origin, i.e. produced in the laboratory by chemical synthesis.
  • the limonene added to the katrafay essential oil may be of natural origin, and preferably may be isolated from botanical species; in another embodiment, the limonene may be of synthetic origin, i.e. produced in laboratory by chemical synthesis.
  • the limonene added to the katrafay essential oil may be D-limonene, L-limonene or a mixture of D-limonene and L-limonene.
  • composition of the invention may be in ozonized or non-ozonized form.
  • the composition may be in ozonized form.
  • ozonized form composition or more simply “ozonized composition” is meant the composition according to the invention, based on katrafay essential oil comprising 20 -40% by weight of ishwarane and, optionally, limonene in the weight ratio with the expected ishwarane, which was effected by an ozonization process.
  • ozone is added at the double bond level of one or more of the isoprenic units present in the terpenes contained in the composition.
  • the ozonized terpenes have a number of favorable biological characteristics, including lower toxicity compared to the corresponding terpenes and the ability to diffuse in biological matrices: for this reason the ozonized form composition represents a preferred embodiment of the invention.
  • the ozonization process is preferably carried out after the possible addition of ishwarane and/or limonene and/or after the possible mixing of the composition with any other vegetable oils; in this way all the present terpenes, both those naturally contained in katrafay oil and those added to obtain the expected quantities, as well as any unsaturated triglycerides present in vegetable oils, are ozonized.
  • ozonation improves the antiinflammatory, lenitive and moisturizing effect of katrafay oil regardless of the specific composition of the invention, since the terpenes in ozonized form, as we said, are more effective in reaching the biological action site and then in carrying out their action.
  • ozonation allows to obtain an even more intense anti-inflammatory, lenitive and moisturizing action.
  • compositions based on katrafay essential oil comprising from 20% to 40% by weight of ishwarane with respect to the total weight of the composition itself and one or more acceptable excipients from pharmaceutical, and/or cosmetic and/or nutritional point of view.
  • the formulation of the invention may further comprise one or more carriers.
  • the excipients and the carriers can be preferably lipophilic or alcoholic, in particular they can be vegetable oils and/or mixtures thereof.
  • the excipients and carriers are chosen appropriately according to the formulation in which the composition will be incorporated, as it is known to a person skilled in the pharmaceutical, cosmetic and/or nutraceutical formulation field.
  • the formulation of the invention can further comprise one or more additional vegetable oils, preferably essential vegetable oils, in particular the lavender essential oil.
  • additional vegetable oils preferably essential vegetable oils, in particular the lavender essential oil.
  • the formulation of the invention can further comprise one or more anti-inflammatory and/or lenitive components.
  • the formulation of the invention can preferably comprise the composition as previously described in a percentage by weight typically included between 0,001% and 40%, preferably between 0,1 % and 10%>. These percentage ranges are applied particularly, but not exclusively, to cosmetic formulations, preferably compositions for topical applications on skin and mucous membranes. With regard to food formulations (for example, supplements or nutraceuticals) they may preferably comprise the composition of the invention in an amount such that the daily administration of the composition is between 30 and 50 mg per kg of weight of the subject.
  • composition of the invention in pure form (i.e. without adding any other excipient, carrier or other ingredient), for example to make "touches” on small areas of the skin and mucous membranes.
  • the formulation comprising the composition according to the invention can take different physical forms, depending on the type of administration to which it is intended.
  • the formulation can be a cream, a gel, a solution, an ointment, a suspension, a formulation in liposomes, a powder, an aerosol, a capsule, a tablet, a pessary, a paste, a spray, a suppository.
  • the formulation can preferably be selected from a cream, a gel and a solution.
  • a solution can for example be represented by a mouthwash, a lavender, ear drops, eye drops.
  • the formulation can preferably be selected from a powder, a capsule and a tablet.
  • the formulation can for example be incorporated into transdermal patches, inhalers, impregnated scaffolds, ointments.
  • the formulation comprising the composition of the invention may be a functional food and/or a supplement and/or a nutraceutical.
  • such functional food, integrator, and/or nutraceutical may be specific for the treatment of inflammation of the locomotor and/or gastrointestinal, and/or nervous apparatus,.
  • Another aspect of the invention relates to a process for preparing the composition according to the invention, which comprises the steps of:
  • step (b) verify the ishwarane title of the essential oil obtained in step (a) and, if necessary, add ishwarane until it reaches a percentage by weight with respect to the total weight of the composition between 20% and 40%;
  • step (b) it is also possible to verify the limonene title of the essential oil obtained in step (a) and, if necessary, add limonene in an amount such that the ratio by weight between ishwarane and limonene in the composition it is between 50: 1 and 100:1.
  • the process described herein may comprise a further step (d) of ozonization of the homogeneous composition obtained in step (c): this further step leads to obtaining a composition based on katrafay essential oil in which the contained terpenes are ozonized.
  • Another aspect of the invention relates to the use of the composition described herein (or to formulations comprising the composition) as cosmetic, and/or as a medicament, and/or as a nutraceutical/supp lenient.
  • the use as a medicament may preferably be in the prevention or treatment of inflammation states. In one embodiment, the states of inflammation may be acute; in another embodiment, the states of inflammation may be chronic.
  • the composition is applied in dermatological field, for the prevention of irritation or inflammation states affecting the skin or mucous membranes.
  • skin irritation or inflammation the composition can be used for example to prevent or treat dermatitis of various types (such as pruriginous and/or seborrhoeic dermatitis), sunburn, insect bites, acne.
  • irritation or inflammation of the mucous membranes the composition can be used, for example, to prevent or treat gingivitis, inflammation of the oral or nasal mucosa, asthma, vaginitis.
  • the composition was also evaluated for use on body sensitive areas and subject to irritation such as the genitals and it was effective and well tolerated.
  • the use as a medicament may preferably be in the treatment of erectile dysfunction, thanks to the vasodilatory properties of the active components of the composition itself.
  • composition according to the invention can be administered, for example, topically or systemically.
  • Topical administration is performed by applying the composition or formulation at the interested site, in an appropriate physical form.
  • An example of topical administration may be the application of the composition or formulation (preferably in the form of a cream, gel, solution) on the skin.
  • Another example of topical administration may be vaginally, preferably where the formulation is in the pessary form.
  • Yet another example of topical administration can be nasally, preferably where the formulation is in the form of a solution or aerosol.
  • Systemic administration can typically occur by mouth and involves formulations comprising the composition; the composition of katrafay oil in pure form is in fact not appropriate for systemic administration.
  • the formulation may therefore preferably have the shape of a capsule, a tablet or a powder.
  • a formulation comprising the composition of the invention can be used as a nutraceutical supplement, incorporating it to a food or a beverage, thus obtaining a functional food.
  • composition according to the present invention is susceptible of numerous modifications and variations, all of which are within the scope of the inventive concept; furthermore, all the details may be replaced by other equivalent elements whose correspondence is known to the person skilled in the art.
  • EXAMPLE 1 ANTIINFIAMMATORY ACTIVITY OF KATRAFAY AND ISHWARANE ESSENTIAL OIL COMPOSITIONS ON CELLS OF THP-1 CELLULAR LINE AT BASIC CONDITIONS.
  • the expression of the inflammatory cytokine TNFa was evaluated by ELISA tests carried out in vitro using cells of the THP- 1 cell line, under basal conditions.
  • Cells were treated in vitro with katrafay essential oil compositions (0,02 ⁇ /ml of cell culture medium), added with ishwarane at different concentrations.
  • the cells were placed for 24 hours in an incubator at a constant temperature of 37°C, with humidity between 90% and 95% and 5% carbon dioxide. After this incubation time, ELISA tests were performed to quantify the production of TNFa by the cells.
  • the ELISA assays were conducted in 96-sink plates according to the indirect sandwich mode: at the bottom of the plate sinks, the capture antibodies are immobilized to bind the TNFa present in the samples when they are deposited in the respective wells; the capture phase is then followed by a series of washings and then by the detection phase which takes place by adding a marked second anti-TNFa antibody with alkaline phosphatase, an enzyme capable of developing the colorimetric reaction that is detected and quantified by spectrophotometric reading. Incubation times and conditions, antibodies and reagents amounts, and spectrophotometric reading mode are those indicated in the ELISA assay kit (Human TNF-a ELISA Kit, Thermo Fisher) used in this experiment.
  • compositions comprising katrafay essential oil and ishwarane, the latter in a concentration between 20% and 40% by weight with respect to the total weight of the composition of essential oil + ishwarane, are found to have maximum anti-inflammatory activity (indicated by the lower production of TNFa).
  • EXAMPLE 2 ANTIINPHIAMMATORY ACTIVITY OF COMPOSITIONS INCLUDING KTRAFAY AND ISHWARANE ESSENTIAL OIL ON THP-1 CELLULAR LINE CELLS AFTER STIMULATION WITH LIPOPOLYSACCHARIDE.
  • THP-1 human monocyte cell line were pre-stimulated with ⁇ g/ml of lipopolysaccharide; 12 hours after pre-stimulation with LPS, THP-1 monocytes were treated with katrafay essential oil compositions (0,02 ⁇ /ml of cell culture medium), added with ishwarane at different concentrations. The cells were placed for 24 hours in an incubator at a constant temperature of 37°C, with humidity ranging between 90% and 95% and 5% carbon dioxide. Once this incubation time has elapsed, ELISA assays have been performed to quantify the production of TNFa by the cells, as described with reference to Example 1.
  • Example 2 With reference to figure 2, it is observed that, even under the experimental conditions of Example 2, which simulate an ongoing acute inflammatory process, the compositions comprising katrafay essential oil (Cedrelopsis grevei) and ishwarane, the latter in a concentration between 20% and 40% by weight with respect to the total weight of the essential oil + ishwarane composition, have the highest antiinflammatory activity (indicated by the lower production of TNFa).
  • katrafay essential oil Cedrelopsis grevei
  • ishwarane the compositions comprising katrafay essential oil (Cedrelopsis grevei) and ishwarane, the latter in a concentration between 20% and 40% by weight with respect to the total weight of the essential oil + ishwarane composition, have the highest antiinflammatory activity (indicated by the lower production of TNFa).
  • EXAMPLE 3 ANTIINFIAMMATORY ACTIVITY OF ISHWARANE AND LEMONENE COMPOSITIONS ON CELLULAR LINE THP-1 AFTER STIMULATION WITH LIPOPOLYSACCHARIDE.
  • THP-1 human monocyte cell line were pre-stimulated with ⁇ g/ml of lipopolysaccharide; 12 hours after pre-stimulation with LPS, the THP-1 monocytes were treated with compositions comprising ishwarane and limonene, whose weight ratio is between 10: 1 and 200: 1.
  • the total amount of the two components was kept equal to 0,002% by weight on the total weight of the cell culture medium in order to compare the result with the reference sample, treated with 0,002% by weight with respect to the total weight of the culture medium of the only ishwarane.
  • the cells were placed for 24 hours in an incubator at a constant temperature of 37°C, with humidity between 90% and 95% and 5% carbon dioxide. Once this incubation time has elapsed, ELISA assays have been performed to quantify the production of TNFa by the cells, as described with reference to Example 1.
  • compositions comprising ishwarane and limonene exert high anti-inflammatory activity (low production of TNFa) when the weight ratio between the two components is between 50: 1 and 100: 1. Outside this range the anti-inflammatory activity decreases significantly even when the ratio shifts in favor of limonene (ishwarane: limonene 10: 1, 20: 1, 35: 1), for which antiinflammatory properties are known and described.
  • the column of the graph marked as "OEK + total ishw:limon 50: 1" represents the composition of the invention, comprising katrafay essential oil, ishwarane and limonene, with an ishwarane weight ratio: limonene 50: 1. The fact that this column is particularly low therefore reflects the synergistic effect of the composition of the invention, which is able to reduce TNFa production far more than ishwarane alone or in combination with limonene.
  • EXAMPLE 4 ANTIINPHIAMMATORY ACTIVITY OF COMPOSITIONS INCLUDING KETRAFAY OIL OF KATRAFAY OZONIZED OR NOT OZONIZED ON CELLS OF THE THP-1 CELLULAR LINE AFTER STIMULATION WITH LIPOPOLYSACCHARIDE.
  • THP-1 human monocyte cell line were pre-stimulated with ⁇ g/ml of lipopolysaccharide; 12 hours after pre-stimulation with LPS, THP-1 monocytes were treated with essential katrafay oil compositions (0,02 ⁇ /ml of cell culture medium), added with ishwarane at different concentrations; for each composition the non- ozonized form and the ozonized form were tested.
  • the cells were placed for 24 hours in an incubator at a constant temperature of 37°C, with humidity between 90% and 95% and 5% carbon dioxide. Once this incubation time has elapsed, ELISA assays have been performed to quantify the production of TNFa by the cells, as described with reference to Example 1.
  • compositions comprising katrafay essential oil and ishwarane have a greater anti-inflammatory activity (indicated by the lower production of TNFa) when the katrafay essential oil is in ozonized form, compared to when it is in non-ozonized form, with equal percentage content of ishwarane.
  • the maximum anti-inflammatory activity occurs in the concentration range of ishwarane ranging from 20% to 40% by weight on the total weight of the composition.
  • EXAMPLE 5 FORMULATION IN THE FORM OF CREAM FOR DERMATOLOGICAL USE INCLUDING KATRAFAY ESSENTIAL OIL
  • the formulation here described, in cream form, can be used in the topical treatment of skin irritation states.
  • EXAMPLE 6 FORMULATION IN THE FORM OF CREAM FOR DERMATOLOGICAL USE (ESPECIALLY DERMATOLOGICAL-GENITAL) INCLUDING KATRAFAY ESSENTIAL OIL.
  • Oryza sativa bran oil 50%
  • sesamum indicum seed oil 12%
  • argania spinosa seed oil 3% - rosa moschata seed oil: 5%
  • the formulation described here in the form of a cream, can be used in the topical treatment of pruriginous dermatitis, particularly in the penis.
  • This formulation is well tolerated at the genital level and compatible with sexual activity, also thanks to a vasodilatory effect, able to contrast problems of erectile dysfunction.

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Abstract

La présente invention concerne une composition à base d'huile essentielle de Katrafay (Cedrelopsis grevei) comprenant de 20 % à 40 % en poids d'ishwarane, par rapport au poids total de la composition. La composition peut éventuellement comprendre également du limonène, dans une quantité telle que le rapport en poids d'ishwarane : limonène est compris entre 50:1 et 100:1. L'invention concerne en outre une formulation comprenant la composition précitée. L'invention concerne également un procédé de préparation de la composition, ainsi que son utilisation comme produit cosmétique, médicament ou complément nutraceutique, en particulier dans le traitement d'états inflammatoires.
PCT/EP2018/071353 2017-08-09 2018-08-07 Composition d'huile essentielle de katrafay et son utilisation comme produit cosmétique, médicament et/ou complément nutritionnel Ceased WO2019030209A1 (fr)

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IT102017000092271A IT201700092271A1 (it) 2017-08-09 2017-08-09 Composizione a base di olio essenziale di katrafay (cedrelopsis grevei) e suo uso come cosmetico, medicamento e/o integratore

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005213202A (ja) 2004-01-29 2005-08-11 Maruzen Pharmaceut Co Ltd 抗酸化剤、抗老化剤及び抗炎症剤、並びに、皮膚化粧料
WO2008034821A1 (fr) 2006-09-20 2008-03-27 Chanel Parfums Beaute Utilisation cosmétique d'agents actifs qui stimulent l'expression de la matriptase

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005213202A (ja) 2004-01-29 2005-08-11 Maruzen Pharmaceut Co Ltd 抗酸化剤、抗老化剤及び抗炎症剤、並びに、皮膚化粧料
WO2008034821A1 (fr) 2006-09-20 2008-03-27 Chanel Parfums Beaute Utilisation cosmétique d'agents actifs qui stimulent l'expression de la matriptase

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CAVALLI JEAN-FRANCOIS ET AL: "Composition and chemical variability of the bark oil of Cedrelopsis grevei H. Baillon from Madagascar", FLAVOUR AND FRAGRANCE JOURNAL., vol. 18, no. 6, November 2003 (2003-11-01), GB, pages 532 - 538, XP055470574, ISSN: 0882-5734, DOI: 10.1002/ffj.1263 *
RAKOTOBE M ET AL: "The bark essential oil composition and chemotaxonomical appraisal of Cedrelopsis grevei H. Baillon from Madagascar", NATURAL PRODUCT COMMUNICATIONS, vol. 3, no. 7, 2008, US, pages 1145 - 1150, XP055470607, ISSN: 1934-578X *
RAKOTOBE MIARANTSOA ET AL: "Bark essential oil of Cedrelopsis grevei from Madagascar: Investigation of steam-distillation conditions", CHEMISTRY & BIODIVERSITY, vol. 11, no. 2, February 2014 (2014-02-01), CH, pages 323 - 331, XP055470602, ISSN: 1612-1872, DOI: 10.1002/cbdv.201300227 *

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