WO2023101546A1 - Cream for protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants - Google Patents

Abstract

The invention belongs to the fields of medicine and dermatocosmetology. A cream for the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants, is proposed. The cream contains Brazil nut oil, squalane of vegetable origin, vitamin E and other ingredients characteristic to creams in specific proportions.

Description

CREAM FOR PROTECTION AND STRENGTHENING OF THE EPIDERMAL LIPID BARRIER OF THE HAND SKIN, WHEN THE SKIN IS FREQUENTLY EXPOSED TO DISINFECTANTS

DESCRIPTION OF INVENTION

[001] The invention is related to the field of medicine and dermatocosmetics and addresses the problem of protecting and strengthening the epidermal lipid barrier of the skin.

BACKGROUND OF INVENTION

[002] The conditions associated with damage to the epidermal lipid barrier of the skin (xerosis, contact dermatitis) represent 95% of all cases of occupational skin diseases. Medical practitioners, hairdressers and catering workers often suffer from occupational contact hand dermatitis caused by damage to the epidermal lipid barrier of the skin, as these professions require frequent hand hygiene and/or prolonged exposure to water [1].

[003] Frequent hand hygiene is required due to the Covid- 19 pandemic caused by a coronavirus disease. The new principles at workplace requiring to disinfect hands and sterilise surfaces apply to different professions: medics, teachers, officials, managers, trade, bank, postal, transport workers and other professions [2]. The recommendations of the World Health Organisation (WHO) issued in the context of the coronavirus pandemic set out the requirements for the prevention of infection: wash hands with soap and water as often as possible [3] . If water and soap are not available, it is recommended to use disposable alcohol napkins or moisturising hygienic napkins and antiseptics/disinf ectants. Frequent hand washing and/or disinfection leads to the destruction of the epidermal lipid barrier of the skin, increased dehydration of the skin, skin dryness, slight exfoliation of stratum comeum, the skin looks scaly. The skin becomes dry, cracks appear, an inflammatory reaction (dermatitis) may develop.

[004] In case of damage to the stratum corneum of the skin, microorganisms, toxins and allergens start penetrating it. Damage to the stratum comeum of the skin is a major stress on the skin. In addition to minor damage to the epidermal barrier and its increased permeability, the epidermal cells start to produce cytokines, which regulate the process of recovery of the stratum corneum. If damage to the stratum comeum is extensive or too frequent, cytokines cause an inflammatory reaction accompanied by damage to epidermal cells by free radicals and oxidative stress [4-6]. The skin becomes hypersensitive, irritated, dehydrated, inflammation and redness appear, the skin becomes less supple, bumpy, loose, bacteria penetrate easier in the damaged skin. Disinfectants also act on the microflora of the hand skin - on the resident and transient microflora. Microorganisms of the resident flora are located under the surface cells of the epithelial stratum corneum - it is a normal resident microflora of a human. The transient microflora gets on the skin as a result of contact with surrounding objects if the personal hygiene rules are not observed and remains on the skin for up to 24 hours. During frequent hand washing and/or use of antiseptics, the transient microflora gets deeper into the skin and expunges the resident microflora that causes the development of dysbacteriosis.

[005] In the process of hygiene or antiseptic treatment, transient microflora is not destroyed, but is simply washed off and distributed with water particles throughout the room, infecting surfaces and equipment.

[006] If the epidermal lipid barrier is disturbed, skin starts to recover within a few minutes [7]. 60% of the damaged barrier normally recovers within 12 hours of destruction, a complete recovery needs three days [4] . If exposure to harmful substances occurs constantly, the skin cannot repair the lipid barrier quickly.

[007] Known use of moisturisers to prevent dry skin. Moisturisers include petrolatum, paraffin, wax, lanolin and other animal fats. They block the penetration of fluid through the stratum corneum of the skin, and transepidermal water loss decreases, while the water content in the stratum corneum increases accordingly. Moisturisers also have a softening effect. The shortcoming of known products is their poor absorption because they cover the skin with a fatty layer with a strong “compress effect”. This leads to blocking and evaporation of moisture, followed by a skin permeability disorder, delaying the recovery of the epidermal barrier [8]. It is recommended to use petrolatum and petrolatum-like fats only in case of acute destruction of the epidermal barrier, when it is necessary to prevent too rapid reaction of skin cells.

[008] Known use of moisturisers such as glycerol, sorbitol, hyaluronic acid, aloe jelly, hydroxylated organic acid capable of capturing and preserving water. These substances form a film on the skin without penetrating it and create a sensation of skin contraction [9] . Hyaluronic acid is a natural biopolymer synthesised by proteins in the body, which is a very strong moisturiser; hyaluronic acid has a large- sized molecule that cannot penetrate deep into the skin, preventing repair of the lipid barrier of the skin. [009] The rate of repair of the lipid barrier is known to be well affected by a lipid mixture containing ceramides, fatty acids and cholesterol in certain proportions [7, 9, [010] Various softeners are used to soften and moisturise the skin suffering from the dry skin syndrome: creams, ointments, oils, emulsions, various soft fats. However, softeners form a film on the surface of the skin, leading to deterioration of the skin permeability and preventing repair of the epidermal lipid barrier of the skin [10, 11].

[011] Known Eucerin cream for dry, rough skin containing urea, ceramides and natural moisturisers [12]. The cream forms a film on the surface of the skin and is not intended for protection and strengthening of the epidermal lipid barrier of the skin, when the skin is frequently exposed to disinfectants.

[012] Known Bepanthen® product [13] containing dexpanthenol, its concentration is 5% in the cream and 2.5% - in the lotion. In the skin cells, this substance is transformed into pantothenic acid - vitamin B5. Pantothenic acid is part of a group of coenzymes (coenzyme A) that plays an important role in acetylation and oxidation processes, accelerates skin recovery processes and helps to restore the balance of its hydrolipidic layer. The Bepanthen® ointment has a medicated effect on dry damaged skin in patients with eczema, it is used for prophylaxis on dry, inflamed and irritated skin. The known product does not ensure the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants.

[013] Known combined product containing 0.1% of methylprednisolone aceponate and ceramides [14] used in the treatment of dermatoses in adults and children. The product contains corticosteroids that are not recommended for regular and long-term use, because they affect the physiological processes of the skin, suppress the recovery process.

[014] Known medicinal product based on a mixture of palmitic acid amides, glycyrrhetinic acid and grape seed extract is intended for the treatment of atopic dermatitis and repair of the skin barrier function [15]. The known compositions are not suitable for the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants.

[015] Known moisturising hand cream Madara® Care Rescue, which helps to maintain the protective barrier of the skin [16]. The cream contains vegetable oils, cranberry, quince and camomile extracts. The irritant ingredient of the cream, alcohol, and the film-forming isoamyl laurate prevents the use of this product for the protection and strengthening of the epidermal lipid barrier of the skin, when the skin is frequently exposed to disinfectants. [016] There is no known cream for the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants.

OBJECT AND SUMMARY OF INVENTION

[017] The object of the invention is to develop a formulation of a cream for the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants. To develop a new cream formulation, it was necessary:

• to search ingredients for the new formulation and their proportions,

• to develop a cream preparation technology.

[018] The purpose of the invention has been achieved because the cream’s ingredients are Brazil nut oil, squalane of vegetable origin, mixture of vegetable oils, hydrogenated lecithin, kojic acid, mixture of plant extracts, medium chain triglycerides, glycerol, pentylene glycol, 75% D-panthenol, vitamin E (alpha-tocopherol), xanthan gum, liquid olive extract, 30% citric acid water solution, aspartic acid and distilled water in the following amounts, g (%):

Brazil nut oil 9.80- 11.00; squalane of vegetable origin 5.90- 6.40 mixture of vegetable oils 4.80 - 5.20; hydrogenated lecithin 3.95 -4.15; kojic acid 2.98 - 3.12: mixture of plant extracts 1.80 -2.20; medium chain triglycerides 1.95 -2.11; glycerol 1.65 - 1.83; pentylene glycol 1.50 - 1.81;

75 % D-panthenol 0.44 -0.56; vitamin E (alpha-tocopherol) 0.28 - 0.32: xanthan gum 0.25 -0.36; liquid olive extract 0.15 -0.25;

30% citric acid water solution 0.05 -0.12; aspartic acid 0.03 - 0.06; distilled water other.

[019] The cream contents is a homogeneous white or white and yellow mass with weakly pronounced and pleasant flavour, which corresponds to the fat base used. All the ingredients of the cream are permitted to be used as dermatological and cosmetic formulations. All the ingredients of the new cream formulation are permitted to be used in dermatocosmetology as individual preparations within the limits of the proportions mentioned in the invention [17, 18, 19].

[020] The cream is intended for the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants.

Features of development of the new cream formulation.

[021] Many experimental studies were conducted to determine ingredients of the new cream. The invention was complicated by the fact that the ingredients of the new formulation, their proportions, in which the new formulation started to have a good effect for the protection and strengthening of the epidermal lipid barrier of the skin, when the skin is frequently exposed to disinfectants, were unknown. 16 ingredients of the formulation, their proportions and technological conditions for getting the cream with a new formulation were discovered experimentally. The conditions of the technology made it possible to prepare a stable, uniform, homogeneous formulation, which keeps its effectiveness and stable consistency at room temperature for up to 8 months.

[022] The formulation of the new cream is a mixture of water and fats, fat-like and other substances, i.e. the contents also include hydrophilic and hydrophobic ingredients. The discovered formulation of fats and fat-like substances ensures the protection and strengthening of the epidermal lipid barrier of the ensuring hand skin, when the skin is frequently exposed to disinfectants. It was technologically complicated to combine so many hydrophilic and hydrophobic ingredients at the same time, because creaming of the finished product was observed in experiments. It was also important to select a special formulation of emulsifiers, the introduction of which in the specified proportions of 16 ingredients of the cream made it possible to get a homogeneous consistency of the new cream and ensured its stability while it was stored. The new cream maintains good elasticity during the storage and packing process in plastic containers. The specified technological properties of obtaining the cream are important for the conditions of use of this cream.

[023] The applied formulation of the new cream is different in that several substances are used as emulsifiers, each of which have structure-forming and emulsifying properties. Specific emulsifiers were introduced in accordance with the technology specified in the invention.

[024] In the experiments, changes in proportions of 16 ingredients in the cream contents caused the loss of homogeneity and elasticity of the cream. Changes in the cream technology caused creaming of the finished product.

The cream formulation contains the following ingredients:

[025] Brazil nut oil has moisturising and healing effects, the oil is an important source of selenium. Selenium has properties of a bioantioxidant, it interacts with vitamins, enzymes, biological membranes in biological systems, activates regenerative processes in the skin, restores the epidermal structure. Brazil nut oil is a hydrophobic substance, the optimal oil content in the new cream formulation is 9.80 - 11.00 g. If the amount of oil contained in the cream is less than 9.80 g, its antioxidant effect decreases. If the amount of oil contained in the cream is more than 11,00 g, there are difficulties in preparing the cream, the consistency of the cream changes, the cream creams, becomes inhomogeneous, which makes it difficult to use.

[026] Squalane of vegetable origin, hydrocarbon of the carotenoid group, is transparent, colourless and odourless oil. Squalane is unsaturated, it is therefore chemically stable and can be stored for more than 2 years, it does not oxidise or stale. In dermatocosmetology, squalane is a high-quality softener, when placed on the skin, squalane easily smears, forming a thin protective film in the form of a lamellar emulsion that prevents loss of moisture and improves the breathing of the skin. Squalane is a hydrophobic substance that actively participates in metabolism, biological synthesis of steroids, has a low antibacterial effect, helps to prevent age spots. The optimal amount of squalane in the new cream formulation is 5.90 to 6.40 g. If the amount of squalane contained in the cream is less than 5.90 g, the skin softening and the skin structure repair effect reduce significantly. If the amount of squalane contained in the cream exceeds 6.40 g, there are difficulties in preparing the cream, the stability of the formulation reduces, the cream creams, which makes it difficult to use.

[027] Vitamin E (alpha-tocopherol) is light yellow transparent viscous liquid with weak flavour. It oxidises and darkens in the light. Tocopherol is a hydrophobic substance found in the green parts of young plants, vegetable oils, a natural antioxidant, participating in the inactivation of free radicals, protecting cell membranes from decay, including under the influence of ultraviolet radiation, participating in protein biosynthesis, making the skin firm and flexible. The inclusion of vitamin E in the cream resulted in a much faster repair of the epidermal lipid barrier of the skin. The optimal amount of vitamin E in the cream formulation is 0.28 - 0.32 g. If the amount of vitamin E is less than 0.28 g, the cream effect significantly reduces, if the amount of vitamin E in the cream formulation is greater than 0.32 g, the consistency of the cream changes, it becomes more liquid, making it difficult to use.

[028] Mixture of vegetable oils: shea butter, which is one of the most valuable vegetable oils, is extracted from the fruits of shea or the karite tree (Vitellaria paradoxa in Latin). Shea butter helps repair the protective lipid film, prevents excessive loss of moisture, softens the skin and gives it flexibility. Crambe Abyssinica seed oil affects directly the epidermis, creating a soft film that gives the skin comfort and protection, and it has a moisturising effect. The optimal amount of the mixture of vegetable oils in the cream formulation is 4.80 - 5.20 g. With a mixture of vegetable oils of less than 4.80 g, the softening effect of the cream decreases significantly, but if the amount of vegetable oil contained in the cream is more than 5.20 g, the consistency of the cream changes, the cream creams, making it difficult to use.

[029] Hydrogenated lecithin is a natural phospholipid, it is an antioxidant that softens and conditions the skin. Lecithin facilitates the penetration of other ingredients into the deeper layers of the skin, in this formulation it is also used as a thickener to make texture of the cream rich. The optimal amount of hydrogenated lecithin in the cream formulation is 3.95- 4.15 g. If the amount of hydrogenated lecithin in the cream formulation is less than 3.95 g, the softening effect significantly reduces, if the amount of hydrogenated lecithin in the cream formulation exceeds 4.15 g, the consistency of the cream thickens, making it difficult to use.

[030] Kojic acid is triglyceride of vegetable origin (crambe Abyssinica seed oil phytosterol ester). In this formulation, it is used as an emulsifier, film-forming and moisturising agent. The optimal amount of kojic acid in the cream formulation is 2.98 - 3.12 g. If the amount of kojic acid in the cream formulation is less than 2.98 g, the moisturising effect decreases significantly, if the amount of kojic acid in the cream formulation exceeds 3.12 g, the emulsification process is disturbed.

[031] Plant extracts include the Pouteria lucuma fruit pulp (Pouteria Lucuma). Lucuma fruit is rich in antioxidants, polyphenols, beta-carotenes, phytosterols, vitamins, fibres, proteins, sugars and minerals. Lucuma oil is a mixture of fatty acids: linoleic acid (38.9%), oleic acid (27.9%), palmitic acid (18.6%), stearic acid (8,9%) and γ-linolenic acid (2.9%). Plant extracts prevent photoaging of the skin caused by oxidative stress, give the skin elasticity, tonicity and density, improve skin texture and give it matte and satin appearance. Yacon juice extract (Polymnia sonchifolid), which rich in fructo-oligosaccharides, acts as a prebiotic for the skin microbiome, thereby improving skin resistance to viral, fungal and bacterial infections. Sodium anisate, a salt of anisic acid, is used as an antimicrobial substance, preservative, natural flavouring. The introduction of this ingredient allowed the abandonment of the use of traditional synthetic and potentially dangerous preservatives releasing formaldehyde. The optimal amount of plant extracts in the cream formulation is 1.80 - 2.20 g. If the amount of plant extracts in the cream formulation is less than 1.80 g, the protective effect decreases significantly, if the amount of plant extracts in the cream formulation exceeds 2.20 g, the cream creams.

[032] Pentylene glycol is a multi-functional glycol containing two alcohol groups OH and a short carbon chain, so it is highly soluble in water, serves as a solvent of lipophilic ingredients. It is capable of capturing moisture and ensuring additional moisturising of the skin and has softening properties. The optimal amount of pentylene glycol in the cream formulation is 1.50 - 1.81 g. If the amount of pentylene glycol in the cream formulation is less than 1.50 g, the moisturising effect decreases significantly, if its amount in the cream formulation exceeds 1.81 g, the emulsion segregates.

[033] Glycerol, trivalent alcohol, belonging to stabilisers, which can maintain and increase the degree of viscosity of the solutions. Glycerol is used as a skin moisturiser in creams, nourishing masks and soap. After using products containing cosmetic glycerol, the skin becomes well moistened and softened, becomes smooth and elastic. The optimal amount of glycerol in the cream formulation is 1.65 - 1.83 g. If the amount of glycerol in the cream formulation is less than 1.65 g, the moisturising effect decreases significantly, if the amount of glycerol in the cream formulation exceeds 1.83 g, the cream causes exfoliation.

[034] Xanthan gum is a plant product with smooth rheology, which ensures that solutions are clear. It is light, loose powder for clear solutions that are stable in a wide range of pH. Xanthan gum is used as a stabilising and structuring ingredient, for the prevention of separation of the hydrophobic phase from the hydrophilic phase of the composition (formulation). The optimal amount of xanthan gum in the cream formulation is 0.25 - 0.36 g. If the amount of xanthan gum in the cream formulation is less than 0.25 g, the emulsion loses stability, if its amount in the cream formulation exceeds 0,36 g, sediments form. [035] 75 % D-panthenol is a provitamin of the D-pantothenic acid (vitamin B5), which plays the main role in the human intermediary metabolism. D-panthenol can be used in almost all cosmetic formulations. It cares for hair, skin and nails. It has a soothing and moisturising effect, reduces skin irritation and contributes very well to the healing of wounds. The optimal amount of D-panthenol in the cream formulation is 0.44 - 0.56 g. If the amount of 75% D-panthenol in the cream formulation is less than 0.44 g, the skin softening and its structure repair effect significantly reduces, if its amount in the cream formulation exceeds 0.56 g, it becomes difficult to prepare the cream, the stability of the formulation reduces, the cream creams making its difficult to use it.

[036] Medium chain triglycerides are oily liquid extracted from coconut oil, are not soluble in water, mix with oils. They improve the application of the cream, dissolve lipophilic ingredients. The recommended amount to be used in the cream is 1.95 - 2.11 g. If the amount of triglycerides in the cream formulation is less than 1.95 g, the stabilising effect significantly reduces, the cream creams, if its amount in the cream formulation exceeds 2.11 g, the consistency of the cream changes, making it difficult to use.

[037] Aspartic acid (aminosuccinic acid) is used as a moisturiser and as a stabiliser. It can usually be found in products for dry skin. Aspartic acid is irreplaceable amino acid, which is naturally found in animals, plants, sugar canes, sugar beets and molasses. The recommended amount to be used in the cream is 0.03 - 0.06 g. If the amount of aspartic acid in the cream formulation is less than 0.03 g, the stabilising effect significantly reduces, the cream creams, if the amount of aspartic acid in the cream formulation exceeds 0.06 g, the consistency of the cream becomes too sticky, making it difficult to use.

[038] 30% citric acid solution is used as a stabiliser and acidity regulator in the finished product. The recommended amount to be used in the cream is 0.05 - 0.12 g. If the amount of 30% citric acid solution in the cream formulation is less than 0.05 g, the stabilising effect significantly reduces, if its amount in the cream formulation exceeds 0.12 g, the pH indicator of the cream changes dropping below the pre-set limit (5.3 - 5.7).

[039] Distilled water is included in the main formulation as an ingredient of the emulsion “water in oil” (where water is the hydrophilic part of the emulsion, fat and oils are the hydrophobic part). The recommended amount of use in the cream formulation is 61.00 - 65.00 g (other). If the amount of distilled water in the cream formulation is less than 61.00 g, the thickening effect significantly reduces, if its amount in the cream formulation exceeds 65.00 g, the consistency of the cream changes, it becomes thicker, making it difficult to use.

[040] All the ingredients of the new cream formulation are approved as individual preparations, within the limits of the proportions mentioned in the invention. The formulation and the preparation technology of the new cream corresponds to the criteria of the safety assessment standard in accordance with the requirements of the European Commission (Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products, Article 11).

[041] Example 1 of the cream formulation:

Brazil nut oil 9.80 g; squalane of vegetable origin 5.90 g; mixture of vegetable oils 4.80 g; hydrogenated lecithin 3.95 g; kojic acid 2.98 g; mixture of plant extracts 1 -80 g; medium chain triglycerides 1.95 g; glycerol 1.65 g; pentylene glycol 1-50 g;

75 % D-panthenol 0.44 g; vitamin E (alpha-tocopherol) 0.28 g; xanthan gum 0.25 g; liquid olive extract 0.15 g;

30% citric acid water solution 0.05 g; aspartic acid 0.03 g; distilled water other.

[042] Example 2 of the cream formulation:

Brazil nut oil 11.00 g; squalane of vegetable origin 6.40 g; mixture of vegetable oils 5.20 g; hydrogenated lecithin 4.15 g; kojic acid 3.12 g; mixture of plant extracts 2.20 g; medium chain triglycerides 2.11 g; glycerol 1.83 g; pentylene glycol 1-81 g;

75 % D-panthenol 0.56 g; vitamin E (alpha-tocopherol) 0.32 g; xanthan gum 0.36 g; liquid olive extract 0.25 g;

30% citric acid water solution 0.12 g; aspartic acid 0.06 g; distilled water other.

Cream technique.

[043] It was difficult to obtain the cream because the ingredients of the new formulation, their proportions, in which the new formulation started to have a good effect for the protection and strengthening of the epidermal lipid barrier of the skin, when the skin is frequently exposed to disinfectants, were unknown. 16 ingredients of the formulation, their proportions and technological conditions for getting the cream with a new formulation were discovered experimentally.

Technique of the first cream formulation.

[044] The cream technique includes the following steps.

[045] 1. Preparing hydrated phospholipids. Place 61.00 g of distilled water, 0.03 g of aspartic acid and 1.65 g of glycerol in a clean container. Get a cold, hydrophilic mixture. Mix 0.25 g of xanthan gum with 1.50 g of pentylene glycol in a separate bowl. Mix the suspension obtained with the cold hydrophilic mixture. Bring the mixture obtained to a homogeneous transparent gel at a temperature of +70 to +75 °C, then add 3.95 g of hydrogenated lecithin. Continue mixing at 30 rpm. Keep the hydrated phospholipid base at a temperature of +70 to 75 °C, and mix the mixture for 20 minutes at an average speed (approximately 300 rpm).

[046] 2. Preparing the hot hydrophobic part of the cream. Slowly melt and mix

4.80 g of mixture of vegetable oils, 1.95 g of medium chain triglycerides and 5.90 g of squalane of vegetable origin in a clean dry container, in a water bath, heating to a temperature of +70 - +75 °C. Then add 9.80 g of Brazil nut oil to the obtained mixture. Mix and stop heating.

[047] 3. Obtaining the emulsion. Add the mixture obtained in step 1 to the hot hydrophobic part, mixing for 3 - 5 minutes at an average speed (approximately 300 rpm). Then the mass obtained is homogenised for 5 minutes at 3000 rpm. Cool the extracted emission to +60 °C, add 0.28 g of vitamin E (alpha-tocopherol) and 0.15 g of liquid olive extract, mix for 5 - 10 minutes at an average speed (approximately 300 rpm). Cool the emulsion to +45°C.

[048] 4. Obtaining the hydrophilic phase. Weigh 1.80 g of the mixture of plant extracts and 0.44 g of 75% D-panthenol in a clean container and mix thoroughly, slowly (30 rpm) add the mixture obtained to the emulsion obtained in step 3 and mix thoroughly. Cool the emulsion obtained to +40° C, then add 2.98 g of kojic acid, mix slowly (30 rpm) for 5 minutes.

[049] 5. Mix the 0.05 g of 30% citric acid water solution obtained at a temperature of +40 °C slowly (30 rpm) and mix it with the previously obtained mixture. Cool the mass to +25 - +30 °C. Determine pH of the obtained mass, it should be within 5.3 - 5.7. Make an adjustment, if necessary, using 30% citric acid water solution.

Technique of the second cream formulation.

[050] The preparation of the cream includes the following steps.

[051] 1. Preparing hydrated phospholipids. Place 65.00 g of distilled water, 0.06 g of aspartic acid and 1.83 g of glycerol in a clean container. Get a cold, hydrophilic mixture. Mix 0.36 g of xanthan gum with 1.81 g of pentylene glycol in a separate bowl. Mix the suspension obtained with the cold hydrophilic mixture. Bring the mixture obtained to a homogeneous transparent gel at a temperature of +70 to +75 °C, then add 3.95 g of hydrogenated lecithin. Continue mixing at 30 rpm. Keep the hydrated phospholipid base at a temperature of +70 to 75 °C, and mix the mixture for 20 minutes at an average speed (approximately 300 rpm).

[052] 2. Preparing the hot hydrophobic part of the cream. Slowly melt and mix

5.20 g of mixture of vegetable oils, 2.11 g of medium chain triglycerides and 6.40 g of squalane of vegetable origin in a clean dry container, in a water bath, heating to a temperature of +70 - +75 °C. Then add 11.00 g of Brazil nut oil to the obtained mixture. Mix and stop heating. [053] 3. Obtaining the emulsion. Add the mixture obtained in step 1 to the hot hydrophobic part, mixing for 3 - 5 minutes at an average speed (approximately 300 rpm). Then the mass obtained is homogenised for 5 minutes at 3000 rpm. Cool the extracted emission to +60 °C, add 0.32 g of vitamin E (alpha-tocopherol) and 0.25 g of liquid olive extract, mix for 5 - 10 minutes at an average speed (approximately 300 rpm). Cool the emulsion to +45°C.

[054] 4. Obtaining the hydrophilic phase. Weigh 2.20 g of the mixture of plant extracts and 0.56 g of 75% D-panthenol in a clean container and mix thoroughly, slowly (30 rpm) add the mixture obtained to the emulsion obtained in step 3 and mix thoroughly. Cool the emulsion obtained to +40° C, then add 3.12 g of kojic acid, mix slowly (30 rpm) for 5 minutes.

[055] 5. Mix the 0.12 g of 30% citric acid water solution obtained at a temperature of +40 °C slowly (30 rpm) and mix it with the previously obtained mixture. Cool the mass to +25 - +30 °C. Determine pH of the obtained mass, it should be within 5.3 - 5.7. Make an adjustment, if necessary, using 30% citric acid water solution.

[056] The cream obtained is packed into 50.0 g opaque containers (plastic containers).

[057] The cream has a good biocompatibility of ingredients, is easily absorbed into the skin, coats it with a thin elastic lamellar layer, pH of the cream is within 5.3 - 5.7. The cream has a softening effect, it reduces hand skin itching and inflammation, protects and strengthens the epidermal lipid barrier, when the skin is frequently exposed to disinfectants. Frequent use of the cream does not irritate the skin and does not cause side effects.

[058] The cream is white, it has soft elastic consistency with a mild nut flavour.

[059] To evaluate properties of the cream with regard to preventing and/or repairing damage of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants, a prospective clinical trial was conducted in the clinic of aesthetic medicine “LIPEX” (Riga). Men and women aged 19 to 75 (study subjects) were invited to participate based on conscious voluntary consent. 2 groups of relatively healthy persons, who complained about hand dryness, were selected. Group 1 (group 1, n = 13, medical employees) included persons, who used hand disinfectants and gloves regularly and frequently (6 - 8 times per day) while performing their professional duties, in particular during the Covid-19 pandemic. Persons from group 2 (group 2, n = 15) used disinfectants rarely, but washed their hands with soap regularly, especially during the Covid-19 pandemic.

[060] The study protocol, the consent and participation protocol and the participation questionnaire meet the Ethical principles of the Declaration of Helsinki for medical trials and were approved by the Ethical Commission of the Riga Stradins University. The parties are not in a conflict of interest.

[061] After the initial visual examination of hand skin, persons of both groups were recommended to use the cream for 4 weeks. The cream was applied in a thin layer 2 times daily (in the morning and in the evening) on clean hands.

[062] To evaluate the epidermal lipid barrier of the skin, the condition and morphology of the skin relief (dryness, exfoliation, turgidity, microrelief) were evaluated using dermatoscopy. The results of the study were calculated and saved using software in the SPSS 20.0 database (Microsoft, US). Numeric results were registered. Each sign was evaluated at a scale from 0 to 3: 0 - no signs, 1 - sign weakly pronounced, 2 - sign moderately pronounced, 3 - sign acutely pronounced.

[063] An improvement of the skin condition was stated as a result of using the new cream in persons of both groups. It was confirmed in the studies that the new cream formulation has cosmetic and prophylactic properties, repairs the epidermal lipid barrier of the hand skin and the barrier function of the skin being studied: improves turgidity and skin moisture, restores elasticity and smooth skin relief, reduces dryness and exfoliation.

[064] Table 1 describes the results of clinical trials in both patient groups.

[065] The invention was complicated by the fact that the ingredients of the new formulation and their proportions, at which the new formulation had effective regenerative effect on the epidermal lipid barrier of the skin, were unknown. The ingredients, their proportions were discovered experimentally. The conditions of the technology of the new cream formulation made it possible to prepare a stable, homogeneous cream, which keeps its effectiveness and stable consistency at room temperature for up to 8 months.

[066] The formulation of the new cream is a mixture of water and fats, fat-like and other substances. High percentage of fats and fat-like substances is important to achieve the effect of repair of the epidermal lipid barrier and its hydrolipidic mantle. It is technologically complicated to combine such amounts of fats without the risk of creaming of the finished product. It is known that almost any fat emulsion may improve the condition of the skin with a damaged barrier to one or another degree. It is known that most of cosmetic emulsions are stabilised by surfactants, and some of them may damage the barrier. This mainly refers to sodium laurilsulfate - an ingredient of many cheap cosmetic and washing agents. Upon repeated contact, many surfactants cause skin irritation and, in particular, dryness and exfoliation. Thanks to the introduction of specific emulsifiers in the new cream formulation, it has been possible to get a lamellar emulsion. Lamellar emulsion imitates the lipid structure of the stratum comeum, melts when applied on the skin and forms a lamellar film, which reduces transepidermal water loss. At the same time, the emulsifiers used provide an effective and stable effect protecting and strengthening the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants.

[067] The formulation of the new cream was not found in any sources of scientific, technical and patent information.

Industrial use

[068] A cream for protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants, has been developed. The cream is packed into 50.00 g and 100.00 g opaque plastic containers. When packed in this way, the cream retains its stability and properties at room temperature for up to 8 months.

Information sources:

1. Morizot F, Guinot C, Lopez J, LaFus I, Tschachler E: Sensitive skin: analysis of symptoms, perceived causes and possible mechanisms. Cosmet Toiletries 2000;115:83-89.

2. Kersh, Anna E. MD, PhD*; Johansen, Maija BAJ; Ojeaga, Ashley MD, MPH§; de la Feld, Salma

Hand Dermatitis in the Time of COVID- 19: A Review of Occupational Irritant Contact Dermatitis, Dermatitis: 3/42021 - Volume 32 - Issue 2 - p 86-93 doi: 10.1097/DER.0000000000000721

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Claims

1. The cream for the protection and strengthening of the epidermal lipid barrier of the hand skin, when the skin is frequently exposed to disinfectants is characterised in that the cream’s ingredients are Brazil nut oil, squalane of vegetable origin, mixture of vegetable oils, hydrogenated lecithin, kojic acid, mixture of plant extracts, medium chain triglycerides, glycerol, pentylene glycol, 75% D-panthenol, vitamin E (alpha-tocopherol), xanthan gum, liquid olive extract, 30% citric acid water solution, aspartic acid and distilled water in the following amounts, g (%):

Brazil nut oil 9.80 - 11.00; squalane of vegetable origin 5.90 - 6.40; mixture of vegetable oils 4.80 - 5.20; hydrogenated lecithin 3.95 -4.15; kojic acid 2.98 - 3.12; mixture of plant extracts 1.80 -2.20; medium chain triglycerides 1.95 -2.11; glycerol 1.65 - 1.83; pentylene glycol 1.50 - 1.81;

75 % D-panthenol 0.44 -0.56; vitamin E (alpha-tocopherol) 0.28 -0.32; xanthan gum 0.25 -0.36; liquid olive extract 0.15 -0.25;

30% citric acid water solution 0.05 -0.12; aspartic acid 0.03 - 0.06; distilled water other.