Field of the Invention

The present invention relates to topical compositions comprising at least one tree nut oil. The invention relates to cosmetic topical compositions which are safely used since the allergic reactions due to the said tree nut oil are prevented.

Background of the Invention

The fetus in the uterus is in a sterile environment, protected from almost all microorganisms and other antigens. Being born into a world where antigens are abundant serves as a powerful stimulus for the development of specific immune mechanisms. However, these and non-specific mechanisms are still not perfect and are absent in newborns and infants. So, newborns and infants are hosts in danger.

Tree nut allergy, which is characterized by immunoglobulin E (IgE) mediated reactions, is the second most common allergy in newborns. Although this allergic reaction that falls into the type-1 hypersensitivity class is thought to be caused by the consumption of tree nuts as food, it is known that allergens that are of protein structure in seeds are also present in seed oils applied topically to the skin, causing allergic reactions to occur.

In one study, almond (Prunus dulcis) oil from the tree nut group was applied to the cheeks and hips of a two-month-old baby, which resulted in dermatitis formation (Guillet G., Guillet MH. 2000. Percutaneous sensitiation to amond oil in infancy and study of ointments in 27 children with food allergy. Allerg Immunol (Paris) 32(8):309-11). In this observation, it is known that the infant has not consumed almonds and that the mother has not eat almonds during the breastfeeding period. This observation therefore suggests a possible percutaneous sensitization to food proteins. In the study, skin ointments containing Prunus dulcis- derived components were applied to 27 newborns with food allergy, indicating the importance of composition selection in topical applications.

Macadamia nuts that also belong to the tree nut group cause lethal anaphylaxis when consumed as food. In addition, contact dermatitis that falls into the type 4 hypersensitivity class has been reported in workers who collect macadamia nuts due to occupational exposure (Knight TE., Hausen BM. 1996 Dermatitis in a nutshell: Occupational exposure to Macadamia integrifolia. Journal of the American Academy of Dermatology 35(3 Pt 1)). Allergens causing contact dermatitis in other members of the Proteaceae family that includes macadamia are known as alkylresorcinols in the literature, although the allergen causing the reaction has not been identified.

WO 99/33479 A1 patent application provides a pharmaceutical composition comprising helminthic parasite for the treatment of IgE mediated diseases, including tree nut allergies. The therapeutic effect provided by the presented composition is based on the principle that allergens of protein structure are broken down by the enzymes of helminth parasites, preventing the immunological response. However, although helminth parasites are attributed as useful to the human body, when considered in the context of newborn health, these parasites pose great risks for the immature infant.

In conclusion, when considered in the context of the problems in the state of art and approaches presented to solve these problems, there is a need in the art for safely administrable compositions, eliminating the risks for allergic reactions due to topical compositions comprising tree nut oils in newborns. Therefore, the selection of all the components in the compositions to be manufactured for this purpose requires very rigorous and detailed studies. The present invention solves these problems with a novel topical composition as set forth in claim 1 and onwards.

Brief Description of the Invention

The present invention provides a topical composition comprising at least one tree nut oil and a Malva Sylvestris extract as a solution to the problems in the state of the art. Said Malva Sylvestris extract is preferably derived from the flower and/or leaves of the plant. It is also advantageous to further use a tocopherol/ascorbyl palmitate mixture to enhance the anti-allergic benefit of Malva Sylvestris extract.

Tree nut oil mentioned herein preferably is the plant(s) or plant(s) oil selected from the group comprising Prunus amygdalus dulcis, Prunus dulcis amara, Bertholletia excelsa, Anacordium occidentale , Castanea, Corylus colurna, Macadamia ternifolia, Carya illinoinensis, Pistacia vera, Pinaceae pinus and Juglans. The said oil, more preferably, belongs to Prunus amygdalus dulcis and/or Macadamia ternifolia plants. The composition more preferably comprises both oils together.

The composition of the invention may further comprise Chamomilla recutita extract and olivoyl hydrolyzed wheat protein. Preferably, the composition further comprises emollients. The said emolients can be selected from Simmondsia Chinensis (Jojoba) seed oil with anti-inflammatory properties and Butyrospermum Parkii (Shea) oil. These emolients can also contain an additional agent selected from glyceryl caprylate and caprylyl glycol.

The composition of the invention can further comprise an emulsifier. Cetearyl alcohol, glyceryl oleate and glyceryl stearate are the preferred emulsifiers. It can further comprise at least one rheology agent wherein rheology agents, preferably, can be selected from xanthan gum and/or hydroxyethylcellulose.

Preferably, pH value of the composition of the invention is between 5.5 and 6.5. For this purpose, it is possible to use a buffering agent, more preferably citric acid.

The physical form of the composition of the invention can be lotion, cream, spray, foam, gel, shampoo or ointment. However, it is particularly preferred that the composition is a baby lotion.

In preferred embodiments, the composition of the invention comprises the following components:

In a further aspect, the invention relates to a process involving a step of mixing at least one tree nut oil with Malva Sylvestris extract to give a composition as described above. More preferably, said method comprises the following steps:

- Mixing water, Chamomilla Recutita extract, at least one chelating agent, Malva sylvestris flower/leaf extract,

- adding hydroxyethylcellulose to the previous mixture,

- dissolving xanthan gum in glycerin and adding to the hydrophobic phase and then mixing, - Obtaining a lipophilic phase comprising olivoyl hydrolyzed wheat protein, stearyl alcohol, glyceryl oleate, glyceryl stearate, Prunus amygdalus dulcis yagi, Macadamia ternifolia nut oil, jojoba oil, lecithin, tocopherol, ascorbyl palmitate and Shea oil and mixing it with previous mixtures,

- mixing the mixture while heating until the emulsion is obtained, and

- cooling and adding phenethyl alcohol, glyceryl caprylate, caprylyl glycol and perfume to the mixture.

The following detailed description will give better insight regarding other embodiments and variations of the invention.

Detailed Description of the Invention

The present invention aims to provide a topical composition that essentially comprises at least one tree nut oil and one Malva Sylvestris extract. As disclosed in the state of the art, tree nuts such as Prunus amygdalus dulcis (sweet almond,) and Macadamia ternifolia (macadamia) and the oils thereof are widely used in topical compositions applied to the skin due to their cosmetically beneficial and nutritive properties. However, since specific proteins in their content cause side effects such as dermatitis, inflammation and irritation, their use in adults, children and infants with sensitive skin is limited. The present invention provides specific combinations comprising the said oils, alleviating and eliminating these disadvantages.

Accordingly, Malva Sylvestris extract used in the present invention reduces the allergic effects of tree nut oils, thus ensuring safe use of the compositions by children and adults with sensitive skin, as well as by newborns and infants.

Malva Sylvestris (great lakes hibiscus), can be used in the treatment of inflammatory diseases in traditional phytotherapy (Kdltur S. 2007. Medicinal plants used in Kirklareli Province (Turkey). Journal of Ethnopharmacology, 111:341-364; Scherrer A.M., R. Motti and C.S. Weckerle. 2005. Traditional plant use in the areas of Monte Vesole and Ascea, Cilento National Park (Campania, Southern Italy). Journal of Ethnopharmacology, 97:129- 143). In a chemical analysis study for Malva Sylvestris showed that the total amount of fatty acids of the flowers and leaves of the plant is mainly composed of omega 3 and omega 6 fatty acids such as linolenic and linoleic acids (Tabaraki R. et al 2012 Chemical Composition and Antioxidant Properties of Malva sylvestris L. Journal of Research in Agricultural Science Vol. 8, No. 1: 59-68). Even though systematic studies regarding the therapeutic properties of omega-3 and omega-6 acids in allergic diseases are limited, studies based on epidemiological observations suggest that such fatty acids play important roles in the prevention of allergic diseases when used as dietary supplements. However, omega-3 supplementation to pregnant women with a fetus at high risk for allergic disease was observed to decrease atopic dermatitis events (Palmer DJ., 2012. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomized controlled trial. BMJ 344: e184).

On the other hand, flavanoids, which act as secondary metabolites in plants, have strong anti-allergic and anti-inflammatory activities. In the chemical analysis study, the flavanoid content in flowers and leaves of Malva Sylvestris was found to be in the range of 21.85- 27.18 and 3.50-4.95 mg CE/gdw. Therefore, Malva Sylvestris, is not only a strong antioxidant but also a potential anti-inflammatory. In the formulations of the invention, it has been suprisingly found that the Malva Sylvestris extract successfully eliminated side effects of tree nut oil in topical application.

It has been observed that this surprising effect provided by the compositions of the present invention is further enhanced when tocopherol/ascorbyl palmitate mixture is used. Tocopherol, also known as Vitamin E, is a collective name for 8 vitamin sets with antioxidant properties. They are present in food to varying degrees. Among these, a- tocopherol and g-tocopherol are the most abundant natural forms of vitamin E, exhibiting opposing regulatory functions during inflammation. Ascorbyl palmitate is the oil soluble form of vitamin C. Vitamin C is also known to exhibit anti-inflammatory effects when taken as a food supplement (Moreno-Macias, H. and Romieu, I. (2014). Effects of antioxidant supplements and nutrients on patients with asthma and allergies. American Academy of Allergy, Asthma & Immunology).

In the present invention, the studies have surprisingly found that allergic reactions are eliminated and the benefits of the active ingredients are maintained when Malva Sylvestris extract and tocopherol/ascorbyl palmitate mixture is used in combination with tree nut oils. Malva Sylvestris extract is preferably derived from leaves and/or flowers of the plant rich in flavanoid and fatty acid.

It has been observed that the strong antioxidant effects of the tocopherol/ascorbyl palmitate mixture synergistically enhance the antiallergic potency of Malva Sylvestris.

As used herein, the term“tree nut” refers to a nut from any tree. The oil derived from the said tree nuts may be derived from a plant seed selected from the group comprising Prunus amygdalus dulcis (sweet almond ), Prunus dulcis amara (bitter almond ), Bertholletia excelsa (Brazil nut), Anacordium occidentale (cashew nut), Castanea (chestnut), Corylus colurna (hazelnut), Macadamia ternifolia (macadamia), Carya illinoinensis (pecan), Pistacia vera (pistachio), Pinaceae pinus (pine nut), Juglans (walnut) and mixtures thereof.

In a preferred embodiment of the present invention, the tree nut oils are derived from a plant seed which are selected from Prunus amygdalus dulcis and Macadamia ternifolia. In a more preferred embodiment of the invention, the topical composition of the invention comprises both oils together.

Preferably, completely natural, herbal ingredients are used in the composition, which is introduced with the present invention considering the sensitive immune systems of newborns. The term“herbal ingredient” as used herein, describes any compound that is derived from a natural resource such as plant and has medical or beneficial effect. In this regard, herbal ingredients might be the extracts and hydrous mixtures, oils and pollenof flowers, nuts, seeds, germs, shells or leaves of plants.

In a preferred embodiment, Chamomilla recutita extract, also known as a type of daisy in the compositions of the present invention, is one of the important herbal ingredients. The desiccated flowers of Chamomilla recutita, which are widely used in skin inflammations, comprise many terpenoits and flavonoids that contribute to the medical features of the plant. Chamomilla recutita flowers also comprise volatile oils (~1 -2%), converting into flavonoids with anti-inflammatory and antiphlogistic features (Srivastava JK., Shankar E. and Gupta S. 2010. Chamomile: A herbal medicine of the past with bright future Mol Med Report. 1; 3(6): 895-901). Furthermore, a study on human subjects demonstrates that Chamomillia flavonoids and essential oils thereof can penetrate into deeper skin layers than the surface of the skin. Furthermore, topical applications of Chamomilla are known to be effective in the treatment of atopic dermatitis.

In another preferred embodiment, olivoyl hydrolysed wheat protein, which is very important for natural products, can be used in compositions. Olivoyl hydrolyzed wheat protein is a naturally occurring surfactant, which is a combination of olive oil and wheat proteins. Combining both herbal oil acid and the protein source gives a new complex with very interesting properties. The protein moiety acts as a protective barrier for the skin, preventing the aggressive attack from other chemicals. It is known that, when the peptides are limited to an average molecular weight of 3500 Da, hydrolysed wheat protein can be used safely in cosmetic products. With regards to the compositions of the present invention, besides having a significance of comprising natural components, the selection of the carrier component should also be made with great care since such excipients can reduce the efficacy of the active ingredient. Irritation and allergic reactions can be caused by the active ingredient as well as by the carrier base of this substance. In a preferred embodiment, jojoba oil, one of the most common oils used as a carrier, has been used. Although appears as an oil, jojoba oil is actually a wax ester derived by the pressing of jojoba seeds. It dissolves in human sebum instantly because of its similarity with human sebum and provides quick penetration of active ingredients to the skin. Additionally, it has anti-inflammatory features. Preferably, another carrier oil is Shea oil. Recently, shea oil has begun to be used as base in medical pomades. Certain isolated chemical components have been reported to have anti-inflammatory, emollient and humectant properties.

The emollients which can be used with the compositions of the present invention can be glyceryl caprylate from the monoglycerides of fatty acids with medium chain (C6-10) and caprylyl glycol from the 2-alkanediols.

Phenethyl alcohol, which is generally used for scent masking dur to its strong flower-like odor, exposes antimicrobial effect when used with glyceryl caprylate and caprylyl glycol. By this means, they exhibit both prophylactic and masking effects. Thus, in a preferred embodiment, the inventors used the combination of phenethyl alcohol, glyceryl caprylate and caprylyl glycol as a masking agent.

In a preferred embodiment of the present invention, the composition further comprises an emulsifier. Emulsifiers enhances kinetic stability of an emulsion. In a preferred embodiment, said emulsifier is selected from the group comprising cetearyl alcohol, glyceryl oleate, glyceryl stearate, and mixtures thereof. Cetearyl alcohol in this group is classified as a fatty alcohol and is used in oil-in-water emulsions to give the skin an emollient feel.

In a preferred embodiment, xanthan gum and hydroxyethylcellulose are used as rheology agent to adjust the viscosity of the emulsion. Xanthan gum is a polysaccharide of high molecular weight formed by pure culture fermentation between carbohydrate and Xanthomonas campestris. It is soluble in hot or cold water and gives solutions of neutral pH that have cloudy appearance. It is soluble in hot glycerol. Solutions thereof are in the range of 1500-2500 cps at 1% concentration. Viscosities thereof are stable between pH 2- 12. Hydroxyethylcellulose (HEC) is an odorless and tasteless powder of light yellowish brown or cream to white colour. It may comprise appropriate anticake agents. It has a density of 0.6 g/mL and a pH of 6-8.5. It gives a clear, colorless solution in hot or cold water. Its viscosity is stable between pH 2 and 12. It is used as a suspension or viscosity agent, binder or film forming agent.

As disclosed in the present description, the composition of the invention is advantageous because of its allergy preventive effects. Examples of tree nut mediated allergies include but not limited to contact dermatitis, atopic dermatitis, non-specific dermatitis, angioedema, urticaria, conjunctivitis, asthma, and anaphylaxis.

From another point of view, the present invention is related to the preparation method of a composition comprising tree nut oils with Malva Sylvestris extract. The method in question includes the step of mixing Malva Sylvestris extract with at least one tree nut oil.

In a preferred embodiment, according to the preparation method of the composition of the present invention, hydrophobic phase components comprising water, Chamomilla Recutita flower extract, at least one chelating agent, Malva sylvestris flower/leaf extract and hydroxyethyl cellulose are mixed. Especially, care is exercised for adding hydroxyethyl cellulose at last, ensuring that all components are added in the composed gel in an appropriate order. Thereafter, separately, xanthan gum is dissolved in glycerin and added to hydrophobic phase and mixed until homogenity is achieved. At the same time, lipophilic phase components comprising olivoyl hydrolyzed wheat protein, Prunus amygdalus dulcis oil, Macadamia ternifolia seed oil, jojoba oil, lecithin, Shea oil and stearyl alcohol are mixed. After the lipophilic phase and hydrophilic phase, it is heated up to 70 °C temperature. Two phases are combined in this process and mixed for 10 minutes until emulsion is obtained. Phenetyl alcohol, glyceryl caprylate and caprylyl glycol are added to the emulsion when the temperature drops down to 40 °C degrees.

Preferably, the physical form of the topical composition of the invention can be lotion, cream, spray, foam, gel, shampoo or ointment. In the most preferred form of the invention, the aforementioned composition is in the form of a baby body lotion and can be applied to baby skin for cosmetic purposes.

According to a preferred embodiment, the content of the composition of the present invention is presented by weight in Table 1. Table 1

A composition of an exemplary product designed as a baby body and face lotion is shown in Table 2 below.

Table 2

Present inventors subjected the composition they obtained to a series of physicochemical tests. These tests are explained by means of the examples below and they are not intended to limit the scope of protection of the invention.

Examples

Example 1

Physicochemical and microbiological data of the obtained formulation are provided in Table 3 below.

Table 3

2

Stability test:

Method: A composition according to Table 2 was stored at various temperatures (4 °C, 25 °C, 40 °C and in weekly thermal shock 4 °C / 40 °C) for 3 months and its stability was evaluated at certain time points (t: 0, day 15, month 1 , month 3). 4 samples that correspond to control days were analyzed for each environmental status. Samples were evaluated at each control time by keeping one sample sealed all the time and others open. Thermal shock was applied once a week in two stages starting in the cooler followed by cooler/heater.

For example, organoleptic and chemical-physical properties at room temperature (25 °C) remained unchanged. Expected and usual changes inherent in the raw materials were not observed under hot and cold conditions. The composition was sealed tightly in order to prevent it from oxidation and possible chemical-physical or temperature-related changes and stored at room temperature.

Conclusion: The composition is stable under reasonable storage conditions (room temperature: 25°C) while used for commercial purposes or in its container for more than 30 months (preserves its chemical and physical properties until the date of expiry).

Example 3

Patch test:

Possible irritation effect of the composition was evaluated according to Draize classification.

Method: A composition that was prepared according to Table 2 was applied to 25 male and female patients between the ages 18-70 that were selected according to the inclusion criteria, i.e. a) well general state of health b) absence of dermatopathy c) absence of ongoing pharmacological treatment d) agreeing to not changing the ordinary daily routine and e) absence of atopy in anamnesis, in order to provide outpatient treatment.

Application of the Examples

According to the ordinary use of the composition, it was applied as a leave on or 10% standard concentration rinse-off composition. Liquid composition was applied to the skin at 20 pi dose. Solid and semi solid composition was applied at a dose of 20 pg. Finn chamber (plastic that contains 7 mm aluminum disc and absorbent paper discs) is a patch test device that provides good occlusion. For liquid compositions, Finn chamber contains blotting papers that were immersed in a certain amount (20 pi) of the sample that will be tested. For solid compositions, the compositions (20 pg) that will be tested are directly applied to the skin.

Application of the Test

The relevant area on the skin (surface of the back) was cleaned using 70% alcoholic solution.

The composition was applied at an amount of 0.02 g or ml/cm ² skin.

The relevant area of the skin was covered by the Finn chamber.

Composition was maintained in contact with the skin for 24 hours.

Finn chamber was removed.

Skin reactions were analyzed at minute 15, hour 1 and 24 after removing the Finn chamber.

Conclusion: It was found that a composition according to Table 2 did not show any irritating effects on the subjects.