LV15082A - Cream for restoring epidermal lipid barrier of the facial skin, neck and decollette area in metabolic syndrome patients - Google Patents

Abstract

Invention relates to the field of dermatology and cosmetology. A composition of a cream for taking care of epidermal lipid barrier of the facial skin, neck and decollette area is provided for. The composition contains seleno-L-methionine, alpha-tocopherol acetate, squalane and other components characteristic to such creams in given proportions.

Description

DESCRIPTION OF THE INVENTION

The invention relates to medicine, is related to family medicine (family practitioners), therapy, endocrinology, gerontology, dermatology and cosmetology, as well as solves the problems of regeneration of epidermal lipid barrier in the skin of the face, neck and décolleté in patients with metabolic syndrome.

TECHNICAL LEVEL

Metabolic Syndrome (MS) - a complex of changes associated with metabolic disorders in which insulin resistance develops, impairing the uptake of glucose in cells. Metabolic syndrome is followed by a complex of different diseases: hypertension, obesity, ischemic heart disease, type 2 diabetes. The development of metabolic syndrome is characterized by an increase in the waist circumference: more than 102 cm for men and more than 88 cm for women. Arterial blood pressure -135/85 mmHg. High levels of lipid peroxidation products in the blood. Oxidants start to activate cellular reactions that destroy proteins, lipids, DNA. The skin's Bavarian function is disturbed and it loses its moisture more intensively, it becomes dry, causing excessive skin flaking, thickening of the skin's horny layer, giving the skin a gray tinge, contributing to the development of various skin diseases: seborrhea, atrophic dermatitis, psoriasis, eczema, etc. diseases [1].

The human body skin is a complex biological tissue system, composed of epidermis, dermis and subcutaneous fat cells. The epidermal basal layer contains melanocytes and Langerhans cells located on the basal membrane. In the epidermal base layer, protoplasm fibers are present, the granular layer forms cells with keratohialin complexes. Derma - the connecting part of the skin, the main skin volume. Derma with basal membrane delimited from the epidermis [2].

The outer part of the epidermis is covered by a layer of horn, on which a water-lipid mantle with a weak acidic environment is formed - a pH of 4.5-5.5. This level of acidity produces bactericidal activity and promotes lipid synthesis. Skin acid properties are associated with sweat and skin fat. Many microbes that get on the skin die in 20-30 minutes [3]. A water-lipid mantle forms an epidermal bay, consisting of horny cells - scales, called comaocytes, among which are epidermal intercellular lipids - ceramides. The ceramides bind the comocytes in an impermeable, 2-piece, epidermal barrier. Ceramic molecules have a polar structure because they have hydrophilic heads (prefer water) and lipophilic tails (prefer fats). The epidermal lipid barrier prevents the penetration of harmful substances into the skin, engages in the regulation of dermal water hemostasis. The lipid barrier consists of cholesterol, ceramides, unsaturated fatty acids (Omega-3, Omega-6). Omega-3 unsaturated fatty acids have anti-inflammatory effects, stimulate Langerhans cells and strengthen the epidermal lipid barrier [4]. Free fatty acids are placed in the lipid layer around the ceramides, they contribute to the water tightness of the skin, form a water-oil emulsion. If the lipid barrier is disturbed, microorganisms, chemical and other exogenous aggressive factors enter the skin. The skin has an immune cell system, with Langerhans cells playing a key role (2-5% cellular epidermis). Langerhans cells are involved in the destruction of bacteria and initiate an immune response involving dermal dendritic cells, epidermal macrophages, etc. Skin aging is associated with the state of the immune system [5]. After the age of 25, the body has a mechanism of natural aging: the amount of macrophages in the skin is reduced, oxidants start to activate cellular reactions, causing protein, lipid and DNA disturbances. particularly active skin accelerated, pathological aging process begins in patients with metabolic syndrome (MS). It is known that metabolic syndrome is accompanied by latent inflammation that causes the activation of peroxidation processes. Accumulation of lipid peroxidation products, lipoprotein and lipid lipid oxidative lesions are manifested as morphological changes in skin structure components [6]. The antioxidant protective system in patients with metabolic syndrome is weakened and / or ineffective. In the case of metabolic syndrome, oxidative stress occurs: keratinocyte formation is impaired, increased transepidermal water loss, dry skin, cracks and erosions. Changes cause imbalances in the microflora of the skin and an increase in the number of fungi, papillomas. Reconstruction of the epidermal lipid barrier in patients with metabolic syndrome is a particular challenge [7]. Table 1 - Analysis of skin epidermal lipid barrier disorders and methods for their detection. 3 Table 1 Analysis of skin epidermal lipid barrier disorders and methods for their detection Clinical manifestations of disturbances Acceleration of transepidermal water loss (caramel) and water content in the epidermal horn layer (corneometry). Skin dryness, peeling, cracks, thickening of the horn layer (hyperkeratosis). Changes in skin acid-alkali balance, pH (pH-metric sensor). Papilloma, skin infection, lipid synthesis disorders. Skin relief and morphological condition (dermatoscopy, microphotography). Skin turgor, micro-oil, papillomas, decreased elasticity, elastosis. Pigmentation and exfoliation (siascopy, mexameters). Lentigo organs and / or pigmentation heterogeneity (dispigmentation). Skin immunity (light microscopy, immunohistochemistry). Immune-competent Langerhans cells, Birbeka pellets, bacteria and / or viruses, papillomas entering the skin. Oils of different areas of the skin (sebumetry). Skin dry, oily, normal, combined. Epidermal proliferation rate (microphotography). Dimensions of comocytes, large comocytes cells in case of skin dehydration. EN 15082 Analysis of skin epidermal lipid barrier disorders is performed through dermatoscopy (skin pH, moisture / drought, grease evaluation) and siachopy (dispigmentation assessment and microrelief examination). Tewameter® TM 300, Courage + Khazaka electronic GmbH, Germany is used to measure transepidermal water loss. The Siaopolis MoleView SIAscope V Handset, Astron, United Kingdom is used to perform the Siachopia. Dermatoscope HEINE alpha + Heine Optotechnic, Germany, is used for dermatoscopy. They are used to analyze the data transmitted to the computer while performing a multi-epidermal lipid barrier characteristic analysis [8-11]: • Corneometry (skin moisture, water content in the epidermal horn layer) is used with the help of the dermatoscope. The principle of comometry is based on the measurement of the electrical capacity of the dielectric environment. Any change in the dielectric constant associated with fluctuations in water content in the upper layers of the skin results in changes in the capacitive characteristics of the measuring system. Moisture is measured on a scale. The basis is water dielectric capacity - 81, distinguishes 4-6 degrees of skin hydration (very high degree of humidity - 45.0-99.9; high, normal - 4 35.1-40.0; lowered, low-20, 1-29.9, dehydrated - below 20.0). • Measurement of transepidermal water loss, measurement of water evaporation from a skin surface based on the diffusion principle in an open chamber. The method is based on measuring partial water pressure in a closed chamber with one humidity sensor. Over time, the partial pressure increase in the chamber is measured. • Acid-base balance, pH-metric. A highly accurate glass electrode is used in the pH-meter sensor. • Sebumetria, a method of sebumetry, is used to detect skin fat in different areas. The method is based on the principle of photometry. A polymer film is used, which is a selective lipid absorbent which is placed in the photometer before and after application of the transmitter on the skin surface. Measurement results are expressed in mkg / cm. Sebumetry rates do not depend on skin moisture. The grease sensor (spongy) consists of three components, one of which is paper - matte, sensitive to fat components, which reacts only to sebum (skin fat), absorbs it, the microprocessor processes the resulting color change, determining the skin type: dry, normal, oily or combined. • Mexameters (assessment of the content of various skin pigments) allows to measure the amount of melatonin pigment in the skin and the degree of erythema. The principle of measurement is based on the fact that the skin absorbs light waves of different lengths in different spectral zones. The Mexometric method is particularly useful for quantifying allergic or inflammatory reactions caused by ultraviolet damage. • Microprint research with microphotography - use of modern digital equipment for skin surface relief and microstructure (wrinkling, smoothness, roughness) with subsequent image retention and comparison, as well as analysis of measurements during the course of treatment. Skin peeling depends mainly on the rate of epidermal proliferation as well as on the balance of the water. Normally, outgoing comocytes are about the same, small in size. The large number of large cells indicates damage to the skin and dehydration.

Known cosmetic compositions for the prevention and treatment of skin dryness in ultraviolet (UV) lesions. Known compositions contain plant extracts and components in combination with various oils [12-14]. It is known that the effect of UV proxy can be corrected with vitamin-antioxidants [15-21]. Known use of retinoids to prevent UV damage [22]. Known cream with selenomethionine for topical 5 EN 15082 use during insolation to protect against skin cancer [23]. Known use of moisturizing creams with high ceramics predominance for children with atopic dermatitis [24],

Use of moisturizing agents to treat dry skin [25-26]. Known use of cream in which tocopherol is an antioxidant to protect the skin from UV damage [27].

Known moisturizing and softening agents that relieve skin dryness, improve skin by moisturizing, but do not restore, as well as solve the problem of epidermal lipid restoration in patients with metabolic syndrome.

Known Vaseline [28], which is used to temporarily replace the damaged skin barrier.

Vaseline and the products based on it are used for medical and cosmetic procedures in which the horn layer is removed, such as laser grinding of the skin, dermabrasion (mechanical removal of the epidermis), peeling.

Vaseline deficiency is poor absorption in the skin as the skin is covered with a greasy layer that complicates its use. Vaseline has a strong occlusive effect (moisture vapor blocking), leading to skin permeability disorders and side effects. Vaseline is recommended to be used only in cases of acute epidermal lesion injury, when it is necessary to prevent a particularly active skin cell reaction that has suddenly lost its external protection, as well as in situations where the skin itself is unable to form a complete barrier. In other cases blocking water evaporation through the damaged horn layer is not recommended.

A known fat emulsion that can simultaneously moisturize and nourish the skin [29]. A known fat emulsion does not have a protective effect on skin aging processes caused by lesions of the skin's radicals in patients with metabolic syndrome.

Known cream with selenium and vitamin E [30], a highly dispersed refined mink oil emulsion in water stabilized with emulsion waxes. The cream does not prevent the lipid barrier being restored in patients with metabolic syndrome. In addition, prolonged use of high-water cream slows down the recovery of the horn layer, which has an adverse effect on the skin in patients with metabolic syndrome [31]. Known different compositions from plant extracts to improve the function of the skin barrier [32-36]. Known compositions do not restore the lipid layer in patients with metabolic syndrome.

No remedy for the restoration of the epidermal lipid barrier in patients with metabolic syndrome is known. 6

DESCRIPTION OF THE INVENTION

Purpose and Technical Purpose of the Invention: Develop a cream composition for regeneration of the epidermal lipid barrier in the facial skin, neck and décolleté area in patients with metabolic syndrome that would prevent the free radical damage to the lipid layer caused by latent inflammation inherent in metabolic syndrome and restore the lipid layer: • new search for composition components and their interrelation, • development of cream making technology, • development of optimal cream form.

The goal is achieved by the fact that the cream contains selenium-L-methionine, α-tocopherol acetate, squalane, methyl-4-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, medium chain triglycerides, white petroleum jelly, macrogol-20-glycerol monostearate, 1, 2-propanediol and purified water. In addition, the cream contains selenium-L-methionine, α-tocopherol acetate, squalane, methyl-4-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, medium chain triglycerides, white petroleum jelly, macrogol-20-glycerin monostearate, 1,2-propanediol and purified water in the following component weight ratios g (%): selenium-L-methionine 0.0005-0.0015; α-tocopherol acetate 0.50-1.50; squalane 11,25-18,75; methyl 4-hydroxybenzoate 0.05-0.15; glycerol monostearate 60 2.52-4.20; cetyl alcohol 3.78-6.29; medium chain triglycerides 4.72-7.87; White Vaseline 16.05-26.74; macrogol-20-glycerol monostearate 4.40-7.34; 1,2-propanediol 6.29-10.49; purified water to 100.0. The cream composition is a homogeneous mass of white or white in color with a yellowish tinge, a weak and pleasant aroma, consistent with the fat base used. All cream components are authorized for pharmaceutical use.

The cream is designed to rejuvenate the epidermal lipid barrier of the face, neck and décolleté patients with metabolic syndrome. 7 LV 15082

The composition of the cream contains the following components:

Selenomethionine (Se-Met (SEM)) - L-enantiomer of selenomethionine, a natural selenium-containing amino acid, is an important source of selenium.

Selenium methionine performs a bioanthoxidate function, interacts with vitamins, enzymes, biological membranes in biological systems and the body as a whole.

Glutathione peroxidase neutralizes oxides and peroxides in enzyme composition, protects cell membranes from collapse, exerts antihistamines, stimulates collagen, keratin biosynthesis, gives skin firmness and elasticity, reduces seborrhea, activates skin regenerative processes, restores skin regenerative processes, restores epidermal structure, restores epidermal structure.

Inorganic selenium, selenium disulfide (Selenium disulfide) is used to treat scalp hair zones in seborrhea [37]. In the US, the standard safe selenium content (from the point of view of intoxication) is 50-220 mcg in the daily diet of an adult, according to studies conducted in China, there was no evidence of daily exposure to 750 mcg of selenium, while symptoms of intoxication were observed when the daily dose was increased to 5,000. mkg / day [38]

Selenium methionine is a hydrophilic substance, the optimum effect of selenium methionine in the cream composition is 0.0005-0.0015 g. If its content is less than 0.0005 g, the antioxidant effect of the cream was reduced, but if its content was higher than 0.0015 g, the cream was difficult to make, the consistency of the cream changed, it was stratified, it was not homogeneous, it made it difficult to use the cream.

Squalane - a naturally occurring hydrocarbon of the carotenoid group, a clear oil free of color and aroma. Squalane does not contain double bonds, so it is chemically stable and can be stored for more than 2 years, it does not oxidize and does not become bitter. Squalane synthesizes in sebaceous glands, one of the main components of skin fat and water-lipid mantle. According to dermatocosmetology, squalene is a high quality emollient (softening agent). Squalane is non-comedogenic, unlike triglycerides and fatty acids in the skin [39-dOJ.

Applying the scalp to the skin, it gently lubricates to form a protective film that protects against moisture loss, improves skin breathing. Thanks to the natural skin contact, squalane easily penetrates through the epidemic, leaving no grease, making the skin soft and silky at the same time. Squalane is a hydrophobic substance that actively engages in metabolism, biological synthesis of steroids, has a mild antibacterial effect and helps prevent age spots. Optimal effect of squalane content in cream composition 11.25-18.75 g. If its content is less than 11.25 g, the effect of softening of the skin structure and 8 regeneration significantly decreased, but if its content is greater than 18.75 g then. there was a problem in the production of the cream, the stability of the composition was reduced, the cream layered and its use was difficult. Vitamin E, α-tocopherol (Vitamin E, Alpha-tocopherol) - light yellow, translucent, viscous liquid with a weak aroma. Light oxidizes and becomes dark. Tocopherol is a hydrophobic substance, it contains the green parts of new plants, vegetable oils, it is a natural antioxidant that participates in inactivation of free radicals, protects cell membranes from collapse, including in the case of ultraviolet radiation, participates in protein synthesis, reduces seborrhea, activates seborrhoea, activates skin \ t regenerative preocesses [41]. The inclusion of Vitamin E in the cream formulation has led to a much faster rejuvenation of the epidermal lipid barrier in patients with metabolic syndrome. Optimal effect of α-tocopherol (vitamin E) content in cream composition 0.50-1.50 g. If its content was less than 0.50 g, the effect was greatly reduced, but if its content was higher than 1.50 g, the consistency of the cream changed, it became considerably more liquid, and difficult to use.

Methyl 4-hydroxybenzoate (Methyl paraben), CH3 (C6H4 (OH) COO) - a white or cream-colored crystalline powder which is poorly soluble in water. It is soluble in warm water, methanol, propylene glycol. It is characterized by a broad spectrum of antibacterial and antifungal activity, which naturally synthesizes in some plants, such as blueberries. It is used against mold and gram-negative bacteria [42]. The human body is easily and completely absorbed through the skin or through the gastrointestinal tract, decomposes into simpler substances and is rapidly excreted in the urine without accumulation in the body. It is used as a stabilizer and / or prolonger, effective in the form of a very low concentration, pure and 0.25% -5% alcohol solution. The optimum effect of the methyl 4-hydroxybenzoate content in the cream composition is 0.05 to 0.15 g. If its content is less than 0.05 g, the stabilizer effect was significantly reduced, but if its content was higher than 0.15 g, the consistency of the cream changed, the insoluble inclusions were noticeable, the use of the cream was difficult.

Glycerine Monostearate 60 (Glycery Stearaie) - a white powder obtained from natural stearic acid and glycerin, with a pearl effect (reflecting light), is a waxy, solid emolent, emulsifier and thickener, added to the mixing phase stabilization process. Used as a stabilizing and structuring component to prevent separation of the hydrophobic and hydrophilic phases of the composition (composition), removal of sediment [43]. If its content was less than 2.52 g, the thickening effect was significantly reduced to 9 9LV 15082, but if its content was higher than 4.20 g, the consistency of the cream changed, the cream became very thick, the use of the cream was difficult.

Cetyl alcohol (1-hexadecanoI), CH3 (CH2) i4CH2OH, mono-fatty alcohol, solid white color, used as a fat-based emulsifier and / or opacifier, which improves consistency, increases the stability of the water-oil mixture [44]. Recommended grams for use: 3.78-6.29 g. If its content is less than 3.78 g, the emulsifier effect decreased significantly, the cream layered, but if its content was greater than 6.29 g, the consistency of the cream changed, the cream became too liquid, the use of the cream was difficult.

Triglycerides medium-cham - an oily solution derived from coconut oil, insoluble in water, miscible with oils [45], Improves the smoothness of cream placement on the skin, dissolves lipophilic compounds. Recommended grams for use: 4.72-7.87 g. If its content is less than 4.72 g, the stabilizer effect decreased significantly, the cream layered, but if its content was higher than 7.87 g, the consistency of the cream changed, the cream became too liquid, which made it difficult to use the cream.

White Vaseline (Vaselinum) is a blend of hard and soft high molecular hydrocarbons obtained by mixing white ceresin and paraffin with perfume oil [46]. Vaseline is used as a thickener in skin cream and ointment. When used externally, Vaseline contributes to the rejuvenation of the skin's water-lipid protector, eliminates fluid loss in the skin cells, prevents skin peeling and cracks. Vaseline is designed to soften the skin of the face and hands, including in cases caused by the effects of external environmental factors (sun, wind, temperature changes). If its content is less than 16.05 g, the thickening effect was greatly reduced, but if its content was higher than 26.74 g, the consistency of the cream changed, the cream became too thick, which made it difficult to use the cream.

Macrogol-20-glycerol monostearate (Macrogol), structural pellet H0- (CH2-CH2-0) nH, white powder, forms hydrogen bonds with water molecules, is used in medicine and cosmetics as a connecting component for making base for ointments, it is also used as a stabilizing agent and a structuring component that makes the composition smooth [47]. The high hydrophilic degree of macrogol allows the homogenization of the composition to be most efficient in an amount of 4.40-7.34 g, emulsifying the hydrophobic components of the new cream. If its content is less than 4.40 g, the thickening effect was greatly reduced, but if its content was higher than 7.34 g, the consistency of the cream changed, the cream became too thick, which made it difficult to use the cream. 10 1,2-Propanediol (1,2-propylenglycol), CH3CH (0H) CH2OH, organic matter, colorless, viscous hydroscopic liquid, odorless, moisture retaining, softening and dispersing agent, good solvent [48]. It completely blends most of the small molecular organic compounds containing oxygen and nitrogen. If its content is less than 6.29 g, the thickening effect was significantly reduced, but if its content was greater than 10.49 g, the consistency of the cream changed, becoming too thick and difficult to use. The water (Aqua) base contains as part of the water-in-oil emulsion (the hydrophilic part of the emulsion, the oil and the squalene - the hydrophobic part). Recommended use: up to 100 g. If its content is less than 33.0 g, the thickening effect was significantly reduced, but if its content exceeded 34.6 g, the consistency of the cream changed, it became too thick, the use of the cream was difficult.

The new cream composition was successfully used to obtain a dosage form of 65.0 g (30.0 g) in tubes. All components of the new cream composition, as separate preparations, are permitted for use in dermatology within the scope of the invention. The composition and manufacturing technology of the new cream complies with the standard criteria for product safety assessment in accordance with European Commission requirements (Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products, Article 11). I.- Π. Examples of cream composition

The composition contains: selenium-L-methionine 0.0005-0.0015; α-tocopherol acetate 0.50-1.50; squalane 11,25-18,75; methyl 4-hydroxybenzoate 0.05-0.15; glycerol monostearate 60 2.52-4.20; cetyl alcohol 3.78-6.29; medium length triglyceride 4.72-7.87; White Vaseline 16.05-26.74; macrogol-20-glycerol monostearate 4.40-7.34; 1,2-propanediol 6.29-10.49; purified water to 100.0. 11 11LV 15082

Cream extraction technique

The complexity of making the new cream composition is due to the fact that squalane, glycerin, triglycerides, vaseline and α-tocopherol are hydrophobic substances, and selenomethionine, macrogol, propanediol - hydrophilic substances.

Method of obtaining the first cream composition 1. Preparation of the hydrophobic part of the cream.

Cream 2.52-4.20 g of glycerol monostearate 60 and 3.78-6.29 g of cetyl alcohol in a water bath at 65-70 ° C in a water bath, add and melt 16.05-26.74 g of Vaseline, add 11, 25-18.75 g of squalane and 4.72-7.87 g of medium chain triglycerides are stirred to homogeneity. The alloy temperature must be 60 ° C. 2. Preparation of the hydrophilic part of the cream.

In a glass beaker, 6.29 to 10.49 g of 1,2-propanediol are dissolved at 0.05 to 0.15 g of methyl 4-hydroxybenzoate at 45-50 ° C, part of the residual purified water is added, stirred, 4.40- 7.34 g of macrogol-20-glycerine monostearate, dissolved by heating to 60 ° C. 3. Add a hydrophilic portion to the hydrophobic portion of the cream preparation vessel, stir the cream in the mixing machine for 15-20 minutes until the mass cools to 30-35 ° C. 4. Add 0.50 to 1.50 g of α-tocopherol acetate and 0.0005-0.0015 g of selenium-L-methionine dissolved in a portion of the remaining purified water to the cream mass. Stir the cream in the mixing machine for 10 minutes to obtain a homogeneous mass.

The method of obtaining the second composition is analogous to the first one. The resulting cream is packed in aluminum tubes of 65.0 g (30.0 g).

The cream is homogenous in white or white with a yellowish tinge, a weak and pleasant aroma, suitable for the fat base used.

The cream is designed to rejuvenate the epidermal lipid barrier of the face, neck and décolleté patients with metabolic syndrome. The cream has a component biocompatibility, it is easily absorbed into the skin, covered with a thin, supple layer, the cream pH 4.0-5.0. The cream has a soothing effect on the skin, it relieves itching and inflammation by prolonged use, it does not cause irritation and side effects.

In order to evaluate the properties of the cream, in connection with the prevention and / or restoration of the epidermal lipid barrier of the skin using the LIPEX (Riga) dermatology clinic and 12 aesthetic medicine base, a prospective clinical study was conducted in which men and women were invited under informative, voluntary consent. with metabolic syndrome aged 39-55 years. As a result, 2 homogeneous groups of patients with non-smoking metabolic syndrome were selected, did not go to the solarium, with a moderate degree of insolation (medium exposure, spent all season in Central and North Europe). The first group (Group 1, n = 12) and the second group (Group 2, n = 15) include patients diagnosed with metabolic syndrome. The diagnosis of metabolic syndrome was based on a complex of changes, according to an analysis by the International Classification of Diseases (10th edition) [1] and the US National Institute of Health: metabolic syndrome was identified by three or more symptoms: • abdominal type of obesity - waist circumference greater than 89 cm for women and over 102 cm for men, • fasting glucose - greater than 6.1 mmol / l, - triglycerides higher than 1.69 mmol / 1, - low density lipoproteins: women less than 1.29 mmol / l; for men - less than 1.04 mmol / l, • arterial blood pressure level of 135/85 mmHg. The protocol of the study, the agreement and the protocol of participation, the participation questionnaire correspond to the ethical and humanist principles of medicine in the World Medical Association (PMA) Helsinki Declaration, as approved by the Riga Stradins University Ethics Commission. There is no conflict of interest. In group 1 patients (n = 12), after a previous clinical trial, the cream was prescribed for a long time (2 months, during active UV insolation, in May and June). The cream was applied in a thin layer twice a day (morning and evening) on a clean face skin, neck and décolleté area. Group 2 patients did not use the cream. In both groups, clinical trials were repeated after 14, 30 and 60 days from the start of the cream application.

Clinical studies included anthropometric data (body mass index, waist circumference, arterial blood pressure), blood test (glucose, lipoproteins). To evaluate the epidermal lipid barrier of the skin, siaskopy and dermatoscopy were performed (mole MoleVievv SIAscope V Handset, Astron, UK and the dermatoscope HEINE alpha + Heine Optotechnic, Germany). The states of skin relief and morphology (turgor, microrelief and the presence of papillomas) were evaluated by dermatoscopy 13 13LV 15082. Pigmentation and peeling were evaluated using siachopy. p-metric measurements were performed with a pH-meter. Measurements of transepidermal water loss were performed with the help of the Tewameter® TM 300, Courage + Khazaka eleclronic GmbH, Germany (camelmeter). The calculation and retention of the study results obtained with these sensors was performed using the software in the database SPSS 20.0 {Microsoft, USA). The results were recorded in numerical values. The range of normal values for corneometry values ranged from 40 and higher, camelmeters below 12, pH-metrics from 3.5 to 5.8. Each attribute was rated on a scale from 0 to 3: 0 - no sign, 2 - sign moderate, 3 - sign strong. Evaluation of structural change data and assessment of skin immunity: histological studies were performed using light microscopy. Magnification of light microscopy - 400 times, by immunohistochemical methods using CDla, CD31, CD34, CD3, CD8. Table 2 - Results of clinical trials of both groups of patients with metabolic syndrome. Table 2 Group 1, New Cream, n = 12 Group 2, No Cream, n = 15 Skin Markers (0-1-2-3 scale) Medium, Medium, Low Moisture Transepidermal Water Loss and Cometry 27, 2 ± 1.1 19.1 ± 1.2 Hatching (by scale 0-1-2-3) Average Index 1.8 Large Dogs 34.4% Average Index 2.6 Large Cells 65.7 + 5% Lentigo, unevenness of pigmentation (by scale 0-1-2-3) Average index 1.2 Average index 2.8 pH Within limits 5.5-5.8 Within limits 5.4-5.6 Skin relief (on scale 0-1 -2-3) Average Index 1.6 Average Index 2.8 14

In the study, most patients in both groups were complaining of dry skin and increased peeling.

As a result of clinical studies, patients of Group 1 patients (12) who took cream for 2 months received the following indicators: 1) skin moisture was 27, 2 ± 1, ie higher than in group 2 patients (15) - 19, 1 ± 1.2; 2) peeling 1.8 was in group 1 patients and 2.6 in group 2 patients i.e. peeling was more pronounced in group 2 patients; 3) pigmentation - 1.2 was in group 1 patients and 2.8 - in group 2 patients, i.e. pigmentation was more pronounced in group 2 patients; 4) skin relief - 1.6 was in group 1 patients and 2.8 was in group 2 patients, i.e. the presence of papillomas and skin elasticity was more pronounced in group 2 patients. Thus, patients in Group 1 who took the new cream within 2 months showed a restoration of skin barrier function, skin relief, and elasticity.

According to data from skin immunity studies, the activity of skin immune cells (Langerhans cell) was reduced in group 2 patients. In addition, lymphocytic infiltration and accumulation of Birbek pellets were observed in the skin of patients in Group 2 (indicative of an inflammatory process). In the skin of Group 1 patients, the number of immunocompetent Langerhans cells increased in the background of the use of the new cream, and the number of Birbeka pellets decreased two times, suggesting an improvement in local skin immunity.

Studies have shown that the new cream composition has cosmetic and curative-prophylactic properties, restores skin epidermal lipid barrier and skin function in patients with metabolic syndrome: improves skin turgor and moisture, restores elasticity and smooth skin texture, reduces pigmentation, inflammation papillomas, inflammatory papillomas .

The complexity of the invention is due to the fact that the new composition components and their interrelationship were not known, so that the new composition would have an effective rejuvenating effect on the epidermal lipid barrier of the skin. The addition of the cream was further complicated by the fact that the components of the new composition were both hydrophilic (selenomethionine) and hydrophobic (vitamin E, squalane) substances. There were no circumstances in which the hydrophilic and hydrophobic components of the new composition could be combined in one cream with a high degree of grease. The experimental components, their relationship and the technological conditions of the new cream 15 15LV 15082 made it possible to produce a stable homogeneous composition of the new cream, which maintains its efficiency and stable consistency at room temperature for 6-8 months.

The composition of the new cream is a mixture of water and fat, fat and other substances. The high percentage of field composition and fatty substances is important in achieving the skin's epidermal lipid barrier and water-lipid restoration effect. There are technological difficulties in connecting such a quantity of fat without the risk of stratification of the finished product. For these types of creams, it is important to use special emulsifiers, the inclusion of which in the proposed application allows to obtain a smooth creamy consistency of the new cream composition, which preserves the stability of the storage process and easy extrusion of the finished dosage form from the package (tubes), which is very important for the convenience of the patient. The different peculiarities of the composition of the new cream applied are the fact that several substances are used as emulsifiers, each of them has structuring and emulsifying properties. At the same time, emulsifiers used in the composition of the cream in a strictly defined order, in accordance with the technology of the claimed invention, provide an effective and stable preservation of the complex composition of the new cream. A certain ratio of hydrophilic components (water, selenomethionine, glycerol) and the ratio of solvents (cetyl alcohol, glycerol) to the activity of hydrophilic (selenomethionine) and hydrophobic (tocopherol, squalane, triglycerides) included in the composition of the cream composition.

The composition of the new cream was not found in scientific-technical and patent information sources. Experimental and Clinical Trials Completed to the 'Invention Level' Criterion

INDUSTRIAL USE

Developed in 2 industrial cream shapes - 65.0 g (30.0 g) in opaque aluminum tubes. Stability and technological properties of both forms of the new cream remain for 6 months at room temperature.

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Claims (2)

CLAIMS 1. Cream for rejuvenation of the epidermal lipid barrier in the facial skin, neck and décolleté regions in patients with metabolic syndrome is characterized by containing selenium-L-methionine, α-tocopherol acetate, squalane, methyl 4-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, medium-chain triglycerides, white petroleum jelly, macrogol-20-glycerin monostearate, 1,2-propanediol and purified water. 2. The cream for the regeneration of the epidermal lipid barrier in the face, neck and décolleté area of patients with metabolic syndrome according to the first claim, comprising selenium-L-methionine, α-tocopherol acetate, squalane, methylmyl-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol. , medium chain triglycerides, white petroleum jelly, macrogol-20-glycerin monostearate, 1,2-propanediol and purified water in the following component weight ratios g (%): selenium-L-methionine 0.0005-0.0015; α-tocopherol acetate 0.50-1.50; squalane 11,25-18,75; methyl 4-hydroxybenzoate 0.05 0.15; glycerol monostearate 60 2.52-4.20; ctyl alcohol 3.78-6.29; medium long chain triglycerides 4.72-7.87; White Vaseline 16.05-26.74; macrogol-20-glycerol monostearate 4.40-7.34; 1,2-propanediol 6.29-10.49; purified water to 100.0.