WO2019209224A2

WO2019209224A2 - Topical compositions for the treatment of dermatitis

Info

Publication number: WO2019209224A2
Application number: PCT/TR2018/050890
Authority: WO
Inventors: Ahmet Toksöz; Zafer Toksöz
Original assignee: Montero Gida Sanayi Ve Ticaret Anonim Sirketi
Priority date: 2017-12-27
Filing date: 2018-12-25
Publication date: 2019-10-31
Also published as: WO2019194775A3; WO2019194775A2; TR201722083A2; WO2019209224A3; TR201806196A2

Abstract

The present invention relates to topical compositions that contain Butyrospermum Parkii (shea) butter and at least one excipient obtained from Helianthus annuus. The invention also relates to the use of these compositions in the treatment of dermatitis and especially dermatitis seen in babies due to diapers.

Description

TOPICAL COMPOSITIONS FOR THE TREATMENT OF DERMATITIS

Field of the Invention

The present invention relates to novel topical compositions for use in the treatment of dermatitis. The invention particularly relates to novel compositions that contain at least one excipient obtained from Helianthus annuus plant and Butyrospermum Parkii (shea] butter.

Background of the Invention

Diaper dermatitis is an irritant dermatitis that develops in the areas that contact the diaper. Many factors such as friction, leaving the skin wet, urine and feces contamination, microorganisms and Candida infection play a role in the etiology of this condition. Since the coefficient of fraction is increased in moist skin, the skin becomes more susceptible to mechanical damage and irritation. This enables irritants to easily penetrate to the stratum corneum layer of the skin. It is clinically characterized by redness, desquamation and papules. Secondary Candida infection frequently develops on diaper dermatitis. In that case, superficial pustules and satellite lesions are seen. Chemical irritants that increase skin pH; soaps, detergents and antiseptics are also among the factors that increase dermatitis. For the treatment of diaper dermatitis, use of topical compositions is recommended as well as precautions such as frequent diaper change and preventing contact with urine.

In state of the art, many synthetic and natural topical compositions have been developed in order to prevent the formation of diaper dermatitis, eliminate or reduce the dermatitis that has developed. Since long-term use of synthetic compositions might harm the skin, natural compositions are rather preferred. In literature, there are studies on various compositions obtained from many plant-based oils and mixtures thereof for the treatment of diaper dermatitis.

Patent application no. US 2004/0131704 A1 provides a natural and organic method for the treatment of diaper dermatitis or other relevant skin irritations. The composition of the invention contains Beeswax, Meadowfoam seed oil, Grape seed oil, Chamomile, Comfrey, Calendula and lavender oil.

Patent no. US 8,932,656 B1 relates to a topical composition that contains Cocos nucifera, olive oil, Jojoba ( Simmondsia chinensis ) oil, Calendula oil, Melaleuca tree oil and Matricaria chamomilla extract for use in skin conditions such as diaper dermatitis. The composition described in this document is intended to overcome problems associated with the distribution of the composition on the skin.

The present invention involves the concomitant use of at least one excipient (plant-based component] obtained from Helianthus annuus plant and Butyrospermum Parkii butter as a natural oil and moisturizer. It was found that the effect in the treatment of dermatitis was boosted further when this composition was used with at least one of Malva sylvestris extract and Calendula officinalis flower extract

Butyrospermum Parkii butter ( shea butter ] that is used in the composition of the present invention is an oil in solid form obtained from the fruits of shea tree. It is rapidly absorbed by the skin and is a natural sunscreen against ultraviolet radiation. Butyrospermum Parkii butter contains many vitamins that the skin needs. It is highly rich in vitamins A, D, E and F. Vitamins A and D boost the skin, while vitamin E rejuvenates the skin. Vitamin F has skin tightening properties. It is used in the treatment of many skin problems such as burns and erythema as well as various allergic conditions such as eczema.

Helianthus annuus that is used in the composition of the present invention is a flowering plant grown for its kernel and oil. It prevents acne and accelerates wound healing. It is also used in healing urticaria and boils as well as against infections.

Malva sylvestris that is used in the present invention has many benefits for skin health in state of the art It is known that it facilitates reducing swelling in the skin. It provides a much more radiant appearance of the skin while rejuvenating skin cells. It delays skin aging and it is used for treatment purposes in wounds and burns on the skin.

Calendula officinalis in the present invention has wound healing properties. It is also used in the treatment of fungal infection, psoriasis and eczema.

The above-mentioned natural oils and mixtures thereof should be formed into a topical dosage form in order to be easily applied on the skin by a patient However, it is not always easy to obtain an effective and safe topical form due to the physical and chemical stability problems of the compositions known in the art that contain natural oils. Since natural oils are not readily soluble in water, phase stability and homogeneity problems are encountered. From the aspect of use by patients, the topical composition should have suitable viscosity, phase stability and homogeneity in order to enable easy application of the composition on the area that will be treated. This composition, which is made into a dosage form, should especially be compatible with the baby's skin and should not cause any harm or a new irritation. Therefore, the composition should also have a pH value within a suitable interval.

In relation to the need for plant-based combinations that provide more stable compositions with improved moisturizing properties, the present invention provides a composition intended to solve the dermatitis problems especially in babies.

Detailed Description of the Invention

The present invention provides a composition that contains Butyrospermum Parkii butter and at least one excipient (plant-based material] obtained from Helianthus annuus that is suitable to be formulated with the mentioned butter. The mentioned composition may optionally contain Malva sylvest s extract and Calendula officinalis flower extract The mentioned composition is especially used in the treatment of diaper dermatitis.

The composition has to meet certain criteria such as suitable pH, viscosity and phase stability in order to obtain an effective and safe topical form of the composition. As mentioned above, a suitable excipient should be used in order to combine the oils of interest and make them into an effective and safe dosage form by meeting these criteria. The mentioned problems were overcome using at least one excipient obtained from Helianthus annuus in the composition of the present invention.

The excipient obtained from Helianthus annuus used within the scope of the present invention can be Helianthus annuus seed oil and/or Helianthus annuus seed cera. This way, it was observed that the desired viscosity value of the topical composition of the invention was achieved. Viscosity value of the composition of the present invention is between 30.000- 50.000 mPas. This viscosity value enables easily applying the topical composition to the desired area as well as enabling the composition to remain in a stable manner on the skin. The composition should penetrate rapidly and effectively, considering it will be covered by a cloth after application on the area. This viscosity value was reached, penetration in the skin was enhanced and the desired effective treatment was achieved by using Helianthus annuus seed oil and Helianthus annuus seed cera in the composition. Therefore, the expression "excipient obtained from Helianthus annuus" used within the scope of the present invention means Helianthus annuus seed oil or Helianthus annuus seed cera or a mixture thereof.

In an embodiment of the invention, the composition also contains Malva sylvestris extract and/or Calendula officinalis flower extract In a preferred embodiment, the composition of the invention contains at least one excipient obtained from Helianthus annuus, and Butyrospermum Parkii butter, Malva sylvest s extract, Calendula officinalis flower extract

In a preferred embodiment of the invention, the excipient obtained from Helianthus annuus contains a combination of Helianthus annuus seed oil and Helianthus annuus seed cera.

The excipient obtained from Helianthus annuus used within the scope of the present invention provides the desired viscosity value and phase stability while also preserving chemical stability. Active ingredient in an effective and safe topical composition should be homogenously distributed within the composition. Insoluble substances or complexes lead to skin irritation. For such unstable topical compositions that exhibit phase separation, the active ingredient cannot be evenly distributed within the area of application. This causes penetration problems on the skin and reduces the effect of treatment. Therefore, the present invention provides a composition that overcomes phase stability and homogeneity problems. The amount of excipient obtained from Helianthus annuus is between 0,5-7% and preferably 3-4% by weight in the total composition.

In an embodiment of the present invention, the amount of Helianthus annuus seed oil is between 1-5% and preferably 3-4% by weight in the total composition. The amount of Helianthus annuus seed cera is between 0,1-1,00%, preferably around 0,2% by weight in the total composition. It was observed that using Helianthus annuus seed oil and Helianthus annuus seed cera in these amounts was effective in reaching the desired viscosity and stability.

The composition of the invention also contains panthenol. The chemical name of panthenol is (2R]-2,4-Dihydroxy-N-(3-hydroxypropyl]-3,3-dimethylbutanamide. In state of the art, panthenol is used in the treatment of wounds on the skin, it stimulates mitotic activity and epithelization, and possesses anti-inflammatory properties. In the composition of the present invention, panthenol was used in order to enhance anti-inflammatory properties of the composition. Besides the therapeutic effects of topical compositions, they also should not cause irritation when applied on the skin. Especially, the properties of compositions applied on the skin of newborns are of utmost importance. In addition, irritation is increased due to the use of agents intended for boosting the anti-inflammatory properties. Panthenol, which is used in the composition of the present invention in order to boost the anti-inflammatory properties, enables obtaining a safe and effective composition. The amount of panthenol in the topical composition of the present invention is between 0,01- 3%, preferably around 1% by weight in the total composition. This amount of panthenol was found to prevent undesired colloidal precipitation and crystallization.

In an embodiment of the invention, the mentioned composition is provided in a form that is selected from the group that comprises ointment, pomade, soap, gel, emulsion, spray, shampoo, mousse, balm, cream and lotion. The compositions of the present invention are more preferably in cream form.

In an embodiment of the present invention, topical composition of the invention may also contain at least one additional agent selected from skin care agents, emollients, solvents, emulsifiers, preservatives, surfactants, humectants, chelating agents, viscosity agents, buffers, antioxidants, perfumes and antimicrobial preservatives.

Suitable skin care agents can be selected from the group that contains glycerin, tocopherol, bisabolol, panthenol, olive oil hydrolyzed wheat protein, caprylyl glycol, zinc oxide and mixtures thereof.

Suitable emollients can be selected from the group that contains glyceryl stearate, glyceryl stearate citrate, glyceryl oleate, polyglyceryl-3-stearate, CIO-18 triglycerides, glyceryl caprilate, glyceryl caprate, cetearyl alcohol, behenyl alcohol, beeswax, lanolin, lecithin, jojoba oil, argania spinosa kernel oil, rosmarinus officinalis oil, triticum vulgare (wheat germ] extract, fish oil, aloe vera oil, rice bran oil, foeniculum vulgare oil, sesame oil, rosehip oil, avocado oil, centella asiatica extract, coconut-caprilate/caprate, fumatrice propolis extract, cremerlin pura and mixtures thereof.

Suitable solvents may be selected from the group that contains water, dicaprylyl ether, glycerol, ethanol, methanol, propylene glycol, polyethylene glycol, 2-propanol, cetyl alcohol, stearyl alcohol, dimethylsulfoxide, benzyl alcohol, 1-3 butylene glycol, polyoxyethylene, lauryl alcohol, 1-3 propanediol and mixtures thereof.

Suitable emulsifiers can be selected from the group that contains carnauba, jojoba, beeswax, lanolin, xanthan gum, lecithin, glyceryl oleate, glyceryl stearate citrate, soapwort, candelilla, castile soap, yucca extract, quince seed, quillaja bark extract, rice bran, lanolin and mixtures thereof.

Suitable preservatives may be selected from the group than contains sodium benzoate, potassium sorbate, rosmarinus officinalis (rosemary] leaf extract, Melaleuca alternifolia leaf oil, hamamelis virginiana (hamamelis] extract, tea tree essential oil, thyme essential oil, grapefruit seed extract, bitter orange extract, propolis extract, caprylhydroxamic acid, caprylyl glycol, glycerin and mixtures thereof.

Suitable surfactants may be selected from the group that contains castile soap, yucca extract, soapwort, quillaja bark extract, lanolin, candelilla, carnauba, jojoba, rice bran, beeswax, lanolin, xanthan gum, quince seed, lecithin, glyceryl oleate, glyceryl stearate citrate and mixtures thereof.

Suitable chelating agents can be selected from the group than contains tetrasodium glutamate diacetate, glutamic acid, ethylenediaminotetraacetic acid (EDTA] or any salt thereof, dimercaprol disodium, deferoxamine and mixtures thereof.

Suitable viscosity agents are selected from the group that contains glycerin, acacia, agar, alginic acid, bentonite, carbomer copolymer, carbomer homopolymer, carbomer interpolymer, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carboxymethylcellulose, carrageenan, microcrystalline cellulose, carboxymethylcellulose sodium, dextrin, gelatin, gellan gum, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, maltodextrin, methylcellulose, pectin, polyethylene oxide, polyvinyl alcohol, povidone, propylene glycol alginate, pullulan, hydrophobic colloidal silica, silicone dioxide, sodium alginate, corn starch, xanthan gum and mixtures thereof.

Suitable buffers are selected from the group than contains citric acid, epolamine, triethanolamine, diethanolamine, tromethamine and mixtures thereof.

Suitable antioxidants are selected from the group that contains lecithin, ascorbyl palmitate, tocopherol, Helianthus annuus oil, ascorbic acid (vitamin C] or ascorbyl palmitate, propolis extract, allium cepae (onion] bulb extract, vitamin E (tocopheryl acetate/tocopherol], licorice (organic licorice] extract and mixtures thereof.

Suitable antimicrobial preservatives are selected from the group that contains propylene glycol, phenoxyethanol, methyl paraben, propyl paraben and salts thereof (sodium, potassium], sodium benzoate, citric acid, benzoic acid, butylated hydroxytoluene, boric acid, sorbic acid, benzyl alcohol, benzalconium chloride, parahydroxybenzoic acids or butylated hydroxyanisole or mixtures thereof.

Topical composition of the present invention is suitable for use in the treatment of dermatitis and especially diaper dermatitis seen in babies. It is suitable for daily use in newborn skin treatment and prevents erythema, irritation and burning. Topical composition of the invention can be applied by massaging as a thin layer at each diaper change. The most effective treatment is achieved by using of the composition of the present invention in this manner.

Another embodiment of the present invention relates to a method for producing a composition of the invention. This method contains the following steps: a] adding Butyrospermum Parkii butter, Helianthus annuus seed oil, and Helianthus annuus seed cera into water and mixing while heating,

b] cooling the mixture until room temperature and obtaining the final product.

In a preferred embodiment of the invention, the mentioned method contains the following steps: a] mixing water, zinc oxide, tetrasodium glutamate diacetate and Malva sylvestris flower extract in a turbo emulsifier,

b] mixing xanthan gum and glycerin until homogeneity is obtained,

c] mixing polyglyceryl-3-stearate, Butyrospermum Parkii butter, Calendula officinalis flower extract, lecithin, Helianthus annuus seed oil, Helianthus annuus seed cera and cetearyl alcohol while heating,

d] combining the phases obtained in steps a, b and c and mixing,

e] leaving the mixture to cool and meanwhile adding bisabolol, panthenol, perfume, caprylyl glycol, phenethyl alcohol, glyceryl caprilate, glyceryl caprate, behenyl alcohol, glyceryl stearate citrate, tocopherol, ascorbyl palmitate, potassium sorbate, sodium benzoate and citric acid while mixing,

f] obtaining the final product

Under these conditions, the production method of the topical composition is easy and low cost.

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 - Cream

Example 2 - Cream

The above-mentioned topical compositions can be prepared by a method that contains the following steps: a] mixing water, zinc oxide, tetrasodium glutamate diacetate and Malva sylvestris flower extract in a turbo emulsifier,

b] mixing xanthan gum and glycerin until homogeneity is obtained,

d] combining the phases obtained in steps a, b and c and mixing,

f] obtaining the end product 3

Stability test:

Method: The composition was stored at various temperatures (4 °C, 25 °C, 40 °C and in thermal shock 4 °C / 40 °C) for 3 months and its stability was evaluated at certain times (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 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) when used for commercial purposes or in its container for more than 30 months (preserves its chemical and physical properties and microbiological compatibility until the date of expiry).

Example 4

Patch test:

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

Method: The test was applied to 25 male-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) acceptance of 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 mΐ 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 mΐ) 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 cleansed using 70% alcoholic solution.

The composition was applied at an amount of 0,02 g or ml/cm² 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; There were no edema and erythema in the patients after the test.

Claims

1. A topical composition that contains Butyrospermum Parkii butter and at least one excipient obtained from Helianthus annuus.

2. The topical composition according to Claim 1, wherein the excipient obtained from Helianthus annuus is selected from Helianthus annuus seed oil and Helianthus annuus seed cera.

3. The topical composition according to Claim 1, wherein the excipient obtained from Helianthus annuus contains a combination of Helianthus annuus seed oil and Helianthus annuus seed cera.

4. The topical composition according to Claim 2 or Claim 3, wherein the amount of the mentioned Helianthus annuus seed oil is between 1-5% by weight in the total composition.

5. The topical composition according to Claim 2 or Claim 3, wherein the amount of the mentioned Helianthus annuus seed cera is between 0,1-1% by weight in the total composition.

6. The topical composition according to Claim 1, wherein the composition also contains Maiva syivestris extract and/or Calendula officinalis flower extract.

7. The topical composition according to Claim 1, wherein the composition also contains panthenol.

8. The topical composition according to Claim 7, wherein the amount of the mentioned panthenol is between 0,01-3% by weight in the total composition.

9. The topical composition according to Claim 1, wherein the composition also contains at least one additional agent selected from skin care agents, emollients, solvents, emulsifiers, preservatives, surfactants, humectants, chelating agents, viscosity agents, buffers, antioxidants, perfumes and antimicrobial preservatives.

10. The topical composition according to Claim 1, wherein the mentioned composition is provided in a form that is selected from the group that comprises ointment, pomade, soap, gel, emulsion, spray, shampoo, mousse, balm, lotion or cream form.

11. The topical composition according to Claim 1, wherein the composition is in cream form.

12. The composition according to any one of the preceding claims, wherein the composition contains the following components:

13. Use of the composition according to any of the preceding claims in the treatment of dermatitis.

14. A composition provided for use according to Claim 13, wherein the mentioned dermatitis is diaper dermatitis seen in babies.

15. A method that contains the following steps for producing a composition according to Claim 1:

adding Butyrospermum Parkii butter, Helianthus annuus seed oil, and

Helianthus annuus seed cera into water and mixing while heating, cooling the mixture until room temperature and obtaining the final product

16. The method for preparing a composition according to Claim 12, wherein it contains the following steps:

a] mixing water, zinc oxide, tetrasodium glutamate diacetate and Malva sylvestris flower extract in a turbo emulsifier,

b] mixing xanthan gum and glycerin until homogeneity is obtained,

d] combining the phases obtained in steps a, b and c and mixing,

f] obtaining the final product.