RU2806599C1 - Cosmetic composition with anti-aging activity to prevent aging and correct age-related changes in skin, its use (options) - Google Patents

Abstract

FIELD: cosmetology.

SUBSTANCE: group of inventions can be used to eliminate acquired cosmetic skin imperfections, rehabilitation of senile skin changes and prevention of age-related skin changes. A cosmetic composition with anti-aging activity for preventing aging and correcting age-related changes in the skin contains a cosmetically or dermatopharmaceutically effective amount of an active component in the form of a composition of senolytics, a composition of peptides, a composition of anti-inflammatory ingredients, a composition of fatty oils, a composition of hyaluronic acids, a composition for the base of a cosmetic composition in the form of emulsifiers, co-emulsifiers, thickeners, humectants, emollients, as well as preservatives, stabilizers and other ingredients. Another embodiment of the composition and the use of a cosmetic composition for preventing aging and correcting age-related changes in the skin are also disclosed.

EFFECT: group of inventions provides an expansion of the arsenal of anti-aging products.

3 cl, 4 dwg, 6 tbl, 8 ex

Description

Field of technology

The invention relates to the field of cosmetology and can be used to eliminate acquired cosmetic skin imperfections, rehabilitation of senile skin changes and prevention of age-related skin changes.

State of the art

Skin aging is caused by the accumulation of senescent cells, the disappearance of the required number of young, healthy cells and is associated with many pathological changes, including the appearance of age-related changes in the form of cosmetic defects, decreased protection against pathogens, increased susceptibility to irritation, delayed wound healing, disruption of normal cellular renewal, synthesis procollagen, collagen, elastin, glycosaminoglycans and increased susceptibility to cancer. Senescent cells secrete a distinct set of proinflammatory mediators called the senescence-associated secretory phenotype (SASP), which can cause profound changes in tissue structure and function. Thus, drugs that selectively eliminate senescent cells or neutralize SASP represent an attractive therapeutic strategy for age-related skin deterioration (Anna Domaszewska-Szostek, Monika Puzianowska-Kuźnicka, and Alina Kuryłowicz. “Flavonoids in Skin Senescence Prevention and Treatment” June 2021International Journal of Molecular Sciences 22(13):6814).

Most cells in the body can undergo cellular senescence. This occurs when a cell has exhausted its allotted limit of cell divisions - replicative aging, or in response to stress or ultraviolet radiation that damage DNA - premature aging.

Aging cells completely stop dividing, but do not die, but are preserved in tissues. At the same time, the work of most intracellular systems in aging cells is disrupted, so they are not able to perform their normal functions. Moreover, senescent cells produce many substances into the extracellular space that can impair the functioning of neighboring cells, causing aging of normal cells or malignant transformation of precancerous cells.

Senescent cells accumulate with age and create cause-and-effect relationships in many age-associated diseases. Senescent cells are resistant to apoptosis and have up-regulation of anti-apoptotic pathways that protect them from their own senescence-associated inflammatory secretory phenotype (SASP), allowing them to survive despite killing neighboring cells.

Cellular aging is the same inevitable process as differentiation, proliferation, apoptosis or necrosis. Senescent cells are in irreversible replicative arrest but remain viable and metabolically active. External and internal signals, including genotoxic and metabolic ones, can lead to aging through cascades of transcription factors (for example, p16HNK4A/retinoblastoma protein and/or p53/p21CIP1). This causes widespread changes in gene expression and organelle function (eg, mitochondria, lysosomes), profound morphological and metabolic shifts, and resistance to apoptosis. This process includes pro-inflammatory, pro-apoptotic cytokines (TNF-α, IL-1α, IL-6, etc.), chemokines that attract, activate and anchor immune cells (IP-10, MCP, etc.), tissue-destructive proteases (e.g. MMP-3, 9 or 12), prothrombotic factors, as well as factors that impair stem/progenitor cell function and cause fibrosis (eg, activin-A-related proteins, TGF-β) and ferritin. In addition to proteins, SASP may include other bioactive molecules (eg, bradykinins, ceramides, prostaglandins), tissue-damaging, proinflammatory, and other factors that contribute to tissue necrosis, fibrosis, systemic inflammation, immune dysfunction, and the progression of aging.

(Song S, Lam EW, Tchkonia T, Kirkland JL, Sun Y. “Senescent cells: emerging targets for human aging and age-related diseases.” Trends Biochem Sci. 2020; 45:578-592.)

The solution to RF patent No. 2640915 “Composition based on flavonoids for pharmaceutical, dietary or cosmetic use with enhanced antioxidant effect” is known. The patent claims a flavonoid-based composition intended for pharmaceutical, dietary or cosmetic use, which has enhanced antioxidant effects against free radicals. The claimed pharmaceutical composition has antioxidant activity against free radicals, it contains: an extract of seeds or seeds and leaves of Vitis vinifera, containing a combination of flavonoids catechin and quercetin in a molar ratio of 6:1 to 3:1, or an extract of seeds or seeds and leaves of Vitis vinifera , containing a combination of flavonoids catechin and quercetin in a molar ratio from 7:1 to 4:1, or a mixture of catechin and quercetin in a molar ratio ranging from 7:1 to 3:1, respectively, together with Olea europaea L. olive leaf extract containing hydroxytyrosol in an amount from 1% to 30% by weight of the extract, or hydroxytyrosol.

The solution to RF patent No. 2743036 “Microcapsule including a peptide having a cell receptor binding affinity and a cosmetic composition containing it” is also known. The invention relates to peptides having the ability to bind to cellular receptors and to a microcapsule including a peptide associated with it, and a cosmetic composition containing the microcapsule. The peptides exhibit high selective binding affinity to the target, and the microcapsule has improved physicochemical stability.

The solution to patent No. 2753515 “Face cream” is also known. The patent contains in the claimed cosmetic composition, wt. %: poria coconut extract with dipeptide and acetyltetrapeptide (active complex SpecKareTMEyeS 100) - 5%, cetearyl olivate and sorbitan olivate - 5%, cyclopentasiloxane - 2%, perfume composition - 0.3%, phenoxyethanol and ethylhexylglycerin - 0.9%, jojoba oil - 2%, hydroxyethylurea - 2%, sodium polyacrylate - 0.5%, butylated hydroxytoluene - 0.03%, purified drinking water - the rest. The described dipeptide is an inhibitor of the conversion of angiotensin I to angiotensin II. As a result of its action, the tone of the walls of blood vessels increases, the production of aldosterone decreases, less fluid is retained in the tissues and swelling decreases, in general it has a vasoconstrictor effect. However, simple vasoconstriction for aging skin does not provide beneficial properties, because aging skin already suffers greatly from impaired blood flow, from deformation of microcirculation, this leads to a decrease in nutrition and oxygen flow to cells, to hypoxia.

Known patent No. 2679649 “Cosmetic composition based on hyaluronic acid, method of its preparation and its use.” The patent talks about the use of peptides in a cosmetic composition. The patent describes the following peptides: tripeptide-32, consists of three amino acids, palmitoyl tripeptide-5 consists of three amino acids, acetylhexapeptide-8, acts to interrupt neuromuscular transmission at the synapse and prevents acetylcholine from contacting the postsynaptic membrane, w-hexapeptide-1 , palmitoyl hexapeptide, a higher activity analogue of argireline.

Known patent No. 2367409 “Antioxidant and antihypoxic complex based on dihydroquercetin for cosmetic products.” The composition contains dihydroquercetin as an antioxidant.

Patent No. 2755201 “Tonic for skin care” relates to cosmetology and is a cosmetic composition for the care of the skin of the face, as well as the neck, décolleté, intended for cleansing, moisturizing and nourishing the skin, including problematic skin, for example, dehydrated skin, having lost firmness and elasticity, becoming flabby. Skin care tonic contains in wt%: sodium hyaluronate - 0.01-2.5; palmityl tripeptide-1 - 0.01-0.15; acetylhexapeptide-8 - 0.01-0.18; palmityl tetrapeptide-4 - 0.05-0.2; palmityl tetrapeptide-7 - 0.01-0.16; copper tripeptide-1 - 1.0-2.5; fructan - 1.2-1.8; raspberry ketone - 0.1-0.5, lotus flower extract - 1.6-2.4; sheep tinder fungus extract - 0.05-0.1; allantoin - 0.1-2.0; niacinamide - 0.1-1.0; sodium citrate - 1.4-2.2; citric acid - 1.2-2.0; lactobionic acid - 1.0-2.0; salicylic acid - 2.0-3.0; preservative - 0.7-2.0; filler - 2.5-4.5; water - the rest. Peptides used: two peptides are tripeptides (each with three amino acids), two peptides are tetrapeptides (each with 4 amino acids), and acetyl hexapeptide - 8. Acetyl Hexapeptide-8 Acetyl hexapeptide - 8 - is a peptide consisting of three amino acids: glutamic, methionic and arginic acid (as described in this patent), has an anti-wrinkle effect (another name for the argireline peptide), as well as a moisturizing/conditioning effect. However, this argireline acts to interrupt neuromuscular transmission at the synapse and prevents acetylcholine from contacting the postsynaptic membrane.

The authors of this application chose this patent No. 2755201 as a prototype, as the closest solution.

Disclosure of the Invention

The objective of the present invention is to create a cosmetic composition with anti-aging activity to correct age-related changes in the skin and to expand the arsenal of similar anti-aging agents.

The technical result is achieved due to the fact that a cosmetic composition with anti-aging activity has been created to correct age-related changes in the skin, which contains a cosmetically or dermatopharmaceutically effective amount of the active component in the form of a composition of senolytics, a composition of peptides, a composition of anti-inflammatory ingredients, a composition of fatty oils, a composition of hyaluronic acids, compositions for the base of a cosmetic composition in the form of emulsifiers, co-emulsifiers, thickeners, humectants, emollients, as well as preservatives, stabilizers and other ingredients in the following ratios of components, wt %:

composition of senolytics from 0.3 to 2.5 peptide composition from 0.00505 to 0.11 composition of anti-inflammatory
ingredients from 1.25 to 11.5 composition of fatty oils from 3.5 to 19 composition of hyaluronic acids from 0.3 to 0.71 preservatives from 0.7 to 1.2 stabilizers from 1.55 to 2.05 composition for the base of a cosmetic composition: emulsifiers, co-emulsifiers, thickeners, humectants, emollients,
solvents from 5.5 to 10.45 other ingredients from 0.161 to 0.17 water rest

(option 1).

In this case, four different ingredients are used as a senolytic composition - fisetin and/or quercetin and/or procyanidin and/or resveratrol, in various combinations, and a dipeptide (D-glutamyl-tryptophan) and/or hexapeptide ( tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine), and/or polypeptide (IL-1) in various combinations, aloe vera gel or juice and/or boswellic acid from purified frankincense resin are used as a composition of anti-inflammatory ingredients, and/or aquacel and/or Barpull G in various combinations; as a composition of fatty oils, apricot kernel oil and/or passionflower oil (passion fruit), and/or macadamia oil, and/or amaranth oil, and/or grape seed oil, and/or evening primrose oil, and/or camellia oil in various combinations; hyaluronic acids of different molecular weights are used as a composition of hyaluronic acids, namely: oligomers of hyaluronic acids with a molecular weight <5 kDa and/or a combination of hyaluronic acids with linolenic acid, and/or hyaluronic acid with a molecular weight of 150-1300 kDa, and/or hyaluronic acid with a molecular weight of 10-150 kDa in various combinations, sodium benzoate, or potassium sorbate, or benzyl alcohol or their various combinations and/or rosemary extract are used as a preservative or a combination of anisic acid with polylysine, sunflower oil with rosemary extract, a combination of different isoforms of vitamin E - α-tocopherol, and/or β-tocopherol, and/or γ-tocopherol, and/or δ-tocopherol, and/ or β-sitosterol, and/or squalene, and/or glyceryl linolenate and/or cetearyl alcohol, and/or 1,2 hexanediol, emulsifiers and/or coemulsifiers, and/or emollients, and/ or thickeners and/or humectants in various combinations; other ingredients include: PH regulator, chelator, odor absorber, fragrance or essential oil.

A cosmetic composition with anti-aging activity has also been created to prevent aging and correct age-related changes in the skin, which contains a cosmetically or dermatopharmaceutically effective amount of the active component in the form of a composition of senolytics, a composition of peptides, preservatives, stabilizers, a composition for the base of a cosmetic composition in the form of emulsifiers, co-emulsifiers, thickeners, humectants, emollients, other ingredients at the following ratios of components, wt%:

composition of senolytics from 0.25 to 1.0 peptide composition from 0.00505 to 0.02 composition for the base of a cosmetic composition: emulsifiers, co-emulsifiers, thickeners, humectants, emollients
solvents from 14.50 to 20.5 preservatives from 0.70 to 1.20 stabilizers 1.8 other ingredients from 0.161 to 0.17 water rest

(option 2).

In this case, quercetin and fisetin are used as a senolytic composition, a dipeptide and/or hexapeptide, and/or polypeptide, in various combinations are used as a peptide composition, emulsifiers and/or coemulsifiers, and/or emollients are used as a composition for the base of a cosmetic composition, and/or thickeners, and/or humectants, or a composition thereof,

sodium benzoate, or potassium sorbate, or benzyl alcohol or various combinations thereof or combinations of anisic acid with polylysine are used as a preservative; cetearyl alcohol and/or 1,2 hexanediol are used as stabilizers; other ingredients are: PH regulator, chelator, perfume/fragrance or essential oil.

The use of cosmetic composition option 1 and option 2 has been proven to prevent aging and correct age-related skin changes.

Brief description of the figures

Figure 1.

Figure 1 shows a picture of the blood supply to the skin through microcapillaries, which reflects the measurement in conventional units of blood flow speed, increased inflow and outflow of blood through the smallest capillaries of the vascular bed of the skin. First, before using the cosmetic composition with formulation No. 1, then after using it for four weeks, twice a day. After applying the cosmetic composition, an increase in the measured value by 1/3 of the initial value is visible, which indicates an increase in the trophic function of the skin under the influence of the cosmetic composition, increased blood supply, oxygen flow into the skin tissue, which proves the anti-aging effect. The Y axis shows the parameters of changes (increases) in microcirculation in conventional units. The X-axis shows the time interval.

Figure 2.

Figure 2 shows the percentage of disappearance of mild acne, and during the application of the cosmetic composition with formulation No. 4, no new acne elements were detected.

2A, 2B - the process of disappearance of pimples (acne) in the studied time interval is displayed. On the Y axis is the percentage of acne regression, on the X axis is the time interval.

2C, 2D - shows the process of increased inflammation after the start of use of a cosmetic composition with rapid healing. The appearance of an increase in the inflammatory process when applying a cosmetic composition is evidence of the activation of pro-inflammatory cytokines under the influence of the cosmetic composition in the epidermis and dermis and the activation of reparative processes aimed at the rapid healing of acne elements and this increase in inflammation is quickly completed with minimal scarring. This indicates the renewal of the cellular composition of the skin, the launch of reparative processes at the site of application of the cosmetic composition. And this also reflects increased microcirculation in the skin.

Figure 3.

The figure shows the pattern of blood supply to the skin through microcapillaries before applying the cosmetic composition (3A), 10 minutes after applying the cosmetic composition (3B), and 20 minutes after applying the cosmetic composition (3C). A cosmetic composition with formulation No. 6 was used.

3A - before applying the cosmetic composition there is a clear unevenness of microcirculation and low blood flow in general. In some places it (black coloring) is absent for a long time.

3B - 10 minutes after applying the cosmetic composition, a more distinct black color appears, but the contours of the curve still remain uneven, as if the blood flow depends on the pulse wave that arrives when the heart contracts.

3C - after 20 minutes, a clear increase in microcirculation is visible with the appearance of a permanent black color and more or less uniform contours. It still depends on the pulse wave, but it is already a stable blood flow of microcirculation, which does not disappear in places, as in previous pictures 3A, 3B.

Figure 4.

Figure 4 - 4A, 4B, 4C - photographs of volunteers who allowed their photographs to be used for placement to confirm the effect of the cosmetic composition. We studied the use of a cosmetic composition with formulation No. 7. These are photographs before using the cosmetic composition - on the left and after 2 months of using the cosmetic composition - on the right.

Implementation of the invention

Two variants of recipes have been created: recipe No. 1, No. 2, No. 3, No. 4 - option 1 and recipe No. 5, No. 6, No. 7 - option 2.

Recipe No. 1 (cosmetic composition 35+):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin
Resveratrol
Procyanidin fisetin
Quercetin
Resveratrol
Procyanidin 1.0
0.15
0.2
0.3 1.65 2 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Dipeptide - D-glutamyl-tryptophan Hexapeptide
Dipeptide 0.01
0.005 0.015 3 Composition against
inflammatory
ingredients Boswellic acids from purified frankincense resin
Aloe vera juice Boswellia Serrata Gum
Aloe Barbadensis Leaf Juice 2.50
2.0 4.50 4 Composition of fatty oils Passionflower oil
Apricot kernel oil
Evening primrose oil
Macadamia oil
Camellia oil
Grape seed oil
Amaranth oil Passiflora Seed Oil
Prunus Armeniaca Kernel Oil
Oenothera Biennis Oil
Macadamia Integrifolia Seed Oil
Camellia Oleifera Seed Oil
Vitis Vinifera (Grape) Seed Oil
Amaranthus Cruentus Seed Oil 2.00
1.00
1.00
0.50
0.50
0.50
0.50 6.00 5 Composition of hyaluronic acids Hyaluronic acid (molecular weight 10 -150 kDa)
Hyaluronic acid (molecular weight 150 - 1300 kDa)
Hyaluronic acid oligomers (molecular weight < 5 kDa)
Hyaluronic acid with linolenic acid Sodium Hyaluronate
Sodium
Hyaluronate
Hydrolyzed
Hyaluronic Acid
Sodium
Hyaluronate (and) Linolenic Acid 0.50
0.10
0.10
0.01 0.71 6 Preservatives Anisic acid and polylysine p-Anisic Acid, Polylysine 1.20 1.20 7 Composition of stabilizers Sunflower oil rosemary extract
Various forms of vitamin E (α-tocopherol, and/or β-tocopherol, and/or γ-tocopherol, and/or δ-tocopherol), and/or β-sitosterol, and/or squalene, and/or glyceryl linolenate
Cetearyl alcohol
1,2 - Hexanediol Helianthus Annuus (Sunflower) Seed Oil (and) Rosmarinus Officinalis (Rosemary) Leaf Extract
α-Tocopherol, β-Tocopherol, γ-Tocopherol, δ-Tocopherol, β-Sitosterol, Squalene, Glyceryl Linolenate
Cetearyl Alcohol
1,2-Hexanediol 0.15
0.10
1.00
0.30 1.55 8 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners, solvents Olivem 1000: cetearyl and sorbitan olivate -
Glycerol
Caprylic triglycerides
Guar gum Cetearyl Olivate (and) Sorbitan Olivate
Glycerin
Caprylic/Capric Triglyceride
Cyamopsis Tetragonoloba (Guar) Gum 5.00
3.00
2.00
0.45 10.45 9 Additional Ingredients Citronellyl methyl crotonate (oil odor absorber)
Chelator - tetrasodium glutamate diacetate
flavoring
pH regulator citric acid Citronellyl Methylcrotonate
Tetrasodium Glutamate Diacetate
Parfum
Citric acid 0.5
0.15
0.01 0.66 10 Water Water Aqua rest

Recipe No. 2 (cosmetic composition 50+):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin
Resveratrol
Procyanidin fisetin
Quercetin
Resveratrol
Procyanidin 1.2
1.00
0.1
0.2 2.50 2 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Dipeptide - D-glutamyl-tryptophan Hexapeptide
Dipeptide 0.02
0.01 0.03 3 Composition against
inflammatory
ingredients Boswellic acids from purified frankincense resin
Aloe vera juice Boswellia Serrata Gum
Aloe Barbadensis Leaf Juice 1.50
10.0 11.50 4 Composition of fatty oils Passionflower oil
Apricot kernel oil
Evening primrose oil
Macadamia oil
Camellia oil
Grape seed oil
Amaranth oil Passiflora Seed Oil
Prunus Armeniaca Kernel Oil
Oenothera Biennis Oil
Macadamia Integrifolia Seed Oil
Camellia Oleifera Seed Oil
Vitis Vinifera (Grape) Seed Oil
Amaranthus Cruentus Seed Oil 3.00
8.00
1.00
3.00
1.00
1.00
2.00 19.0 5 Composition of hyaluronic acids Hyaluronic acid (molecular weight 10 -150 kDa)
Hyaluronic acid (molecular weight 150 - 1300 kDa)
Hyaluronic acid oligomers (molecular weight < 5 kDa)
Hyaluronic acid with linolenic acid Sodium Hyaluronate
Sodium
Hyaluronate
Hydrolyzed
Hyaluronic Acid
Sodium
Hyaluronate (and) Linolenic Acid 0.50
0.10
0.10
0.01 0.71 6 Preservatives Potassium sorbate
Sodium benzoate Potassium sorbate
Sodium Benzoate 0.50

0.50 1.00 7 Composition of stabilizers Sunflower oil, rosemary extract
Various forms of vitamin E (α-tocopherol, and/or β-tocopherol, and/or γ-tocopherol, and/or δ-tocopherol), and/or β-sitosterol, and/or squalene, and/or glyceryl linolenate
Cetearyl alcohol
1,2 - Hexanediol Helianthus Annuus (Sunflower) Seed Oil (and) Rosmarinus Officinalis (Rosemary) Leaf Extract
α-Tocopherol, β-Tocopherol, γ-Tocopherol, δ-Tocopherol, β-Sitosterol, Squalene, Glyceryl Linolenate
Cetearyl Alcohol
1,2-Hexanediol 0.15
0.10
1.50
0.30 2.05 8 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners, solvents Pufos alpha
Arginine
Glycerol
Caprylic triglycerides
Xanthan gum Purephose a
Arginine
Glycerin
Caprylic/Capric Triglyceride
Xanthan Gum 2.00
1.00
3.00
2.00
0.50 8.50 9 Additional Ingredients Citronellyl methyl crotonate (oil odor absorber)
Chelator - tetrasodium glutamate diacetate
Perfume/flavor
pH regulator citric acid Citronellyl Methylcrotonate
Tetrasodium Glutamate Diacetate
Parfum
Citric acid 1.00
0.15
0.01
0.1 1.26 10 Water Water Aqua rest

Recipe No. 3 (cosmetic composition 30+):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin
Resveratrol
Procyanidin fisetin
Quercetin
Resveratrol
Procyanidin 0.25
0.15
0.5
0.5 1.4 2 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Polypeptide - IL-! Hexapeptide
Polypeptide 0.1
0.00005 0.10005 3 Composition against
inflammatory
ingredients Aloe vera juice Aloe Barbadensis Leaf Juice 2.0 2.00 4 Composition of fatty oils Passionflower oil
Apricot kernel oil
Evening primrose oil
Macadamia oil
Camellia oil
Grape seed oil
Amaranth oil Passiflora Seed Oil
Prunus Armeniaca Kernel Oil
Oenothera Biennis Oil
Macadamia Integrifolia Seed Oil
Camellia Oleifera Seed Oil
Vitis Vinifera (Grape) Seed Oil
Amaranthus Cruentus Seed Oil 1.00
1.00
0.50
0.50
0.25
0.50
0.25 4.0 5 Composition of hyaluronic acids Hyaluronic acid (molecular weight 10 -150 kDa)
Hyaluronic acid (molecular weight 150 - 1300 kDa)
Hyaluronic acid oligomers (molecular weight < 5 kDa)
Hyaluronic acid with linolenic acid Sodium Hyaluronate
Sodium
Hyaluronate
Hydrolyzed
Hyaluronic Acid
Sodium
Hyaluronate (and) Linolenic Acid 0.10
0.10
0.10
0.01 0.31 6 Preservatives Potassium sorbate
Sodium benzoate Potassium sorbate
Sodium Benzoate 0.50
0.50 1.00 7 Composition of stabilizers Sunflower oil, rosemary extract
Various forms of vitamin E (α-tocopherol, and/or β-tocopherol, and/or γ-tocopherol, and/or δ-tocopherol), and/or β-sitosterol, and/or squalene, and/or glyceryl linolenate
Cetearyl alcohol
1,2 - Hexanediol Helianthus Annuus (Sunflower) Seed Oil (and) Rosmarinus Officinalis (Rosemary) Leaf Extract
α-Tocopherol, β-Tocopherol, γ-Tocopherol, δ-Tocopherol, β-Sitosterol, Squalene, Glyceryl Linolenate
Cetearyl Alcohol
1,2-Hexanediol 0.15
0.10
1.50
0.30 2.05 8 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners, solvents Pufos alpha
Arginine
Glycerol
Caprylic triglycerides
Xanthan gum Purephose a
Arginine
Glycerin
Caprylic/Capric Triglyceride
Xanthan Gum 1.30
0.65
3.00
2.00
0.50 7.45 9 Additional Ingredients Citronellyl methyl crotonate (oil odor absorber)
Chelator - tetrasodium glutamate diacetate
Perfume (may be missing)
pH regulator citric acid Citronellyl Methylcrotonate
Tetrasodium Glutamate Diacetate
Parfum
Citric acid 0.02
0.15
0.01 0.66 10 Water Water Aqua rest

Recipe No. 4 (cosmetic composition 25+):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin
Resveratrol
Procyanidin fisetin
Quercetin
Resveratrol
Procyanidin 0.10
0.10
0.05
0.05 0.3 2 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Dipeptide - D-glutamyl-tryptophan Hexapeptide
Dipeptide 0.01
0.01 0.02 3 Composition against
inflammatory
ingredients Boswellic acids from purified frankincense resin
Aloe vera juice Boswellia Serrata Gum
Aloe Barbadensis Leaf Juice 0.25
1.0 1.25 4 Composition of fatty oils Passionflower oil
Apricot kernel oil
Evening primrose oil
Macadamia oil
Camellia oil
Grape seed oil
Amaranth oil Passiflora Seed Oil
Prunus Armeniaca Kernel Oil
Oenothera Biennis Oil
Macadamia Integrifolia Seed Oil
Camellia Oleifera Seed Oil
Vitis Vinifera (Grape) Seed Oil
Amaranthus Cruentus Seed Oil 1.00
1.00
0.25
0.50
0.25
0.25
0.25 3.50 5 Composition of hyaluronic acids Hyaluronic acid (molecular weight 10 -150 kDa)
Hyaluronic acid (molecular weight 150 - 1300 kDa)
Hyaluronic acid oligomers (molecular weight < 5 kDa) Sodium Hyaluronate
Sodium
Hyaluronate
Hydrolyzed
Hyaluronic Acid 0.10
0.10
0.10 0.30 6 Preservatives Potassium sorbate
Sodium benzoate Potassium sorbate
Sodium Benzoate 0.3
0.4 0.7 7 Composition of stabilizers Sunflower oil, rosemary extract
Various forms of vitamin E (α-tocopherol, and/or β-tocopherol, and/or γ-tocopherol, and/or δ-tocopherol), and/or β-sitosterol, and/or squalene, and/or glyceryl linolenate
Cetearyl alcohol
1,2 - Hexanediol Helianthus Annuus (Sunflower) Seed Oil (and) Rosmarinus Officinalis (Rosemary) Leaf Extract
α-Tocopherol, β-Tocopherol, γ-Tocopherol, δ-Tocopherol, β-Sitosterol, Squalene, Glyceryl Linolenate
Cetearyl Alcohol
1,2-Hexanediol 0.15
0.10
1.50
0.30 2.05 8 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners, solvents Pufos alpha
Arginine
Glycerol
Caprylic triglycerides
Xanthan gum Purephose a
Arginine
Glycerin
Caprylic/Capric Triglyceride
Xanthan Gum 2.0
1.0
3.00
2.00
0.50 8.50 9 Additional Ingredients Citronellyl methyl crotonate (oil odor absorber)
Chelator - tetrasodium glutamate diacetate
Flavoring
pH regulator citric acid Citronellyl Methylcrotonate
Tetrasodium Glutamate Diacetate
Parfum
Citric acid 1.00
0.15
0.01
0.1 1.26 10 Water Water Aqua rest

Recipe No. 5 (cosmetic composition around the eyes):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin fisetin
Quercetin 0.15
0.15 0.3 1 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Polypeptide - IL-1 Hexapeptide
Polypeptide 0.005
0.00005 0.00505 2 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners, solvents Pufos alpha
Arginine
Glycerol
Caprylic triglycerides
Squalane
Xanthan gum Purephose a
Arginine
Glycerin
Caprylic/Capric Triglyceride
Squalane
Xanthan Gum 2.0
1.0
5.00
7.00
2.00
0.50 14.50 + 3 Preservatives Potassium sorbate
Sodium benzoate Potassium sorbate
Sodium Benzoate 0.3
0.4 0.70 4 Composition of stabilizers Cetearyl alcohol
1,2 - Hexanediol Cetearyl Alcohol
1,2-Hexanediol 1.50
0.30 1.80 5 Other Ingredients Chelator - tetrasodium glutamate diacetate
Perfume essential oil of palmarosa
pH regulator citric acid Tetrasodium Glutamate Diacetate
Parfum Cymbopogon Martini Essential Oil*
Citric acid 0.15
0.001
0.01 0.161 6 Water Water Aqua rest

Recipe No. 6 (cosmetic composition around the eyes):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin fisetin
Quercetin 0.25
0.45 0.7 1 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Dipeptide - D-glutamyl-tryptophan Hexapeptide
Dipeptide 0.01
0.01 0.02 2 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners, solvents Olivem 1000: cetearyl and sorbitan olivate
Glycerol
Caprylic triglycerides
Squalane
Xanthan gum Cetearyl Olivate (and) Sorbitan Olivate
Glycerin
Caprylic/Capric Triglyceride
Squalane
Xanthan Gum 5.00
3.00
2.00
5.00
0.50 15.50 3 Preservatives Potassium sorbate
Sodium benzoate Potassium sorbate
Sodium Benzoate 0.5
0.5 1.00 4 Composition of stabilizers Cetearyl alcohol
1,2 - Hexanediol Cetearyl Alcohol
1,2-Hexanediol 1.50
0.30 1.80 5 Additional Ingredients Chelator - tetrasodium glutamate diacetate
Flavoring
pH regulator citric acid Tetrasodium Glutamate Diacetate
Parfum
Citric acid 0.15
0.01
0.01 0.17 6 Water Water Aqua rest

Recipe No. 7 (cosmetic composition around the eyes):

No. Name Name
Components
Rus. Name
Components
Lat. Qty
% Sum
% 1 Composition of senolytics Fisetin
Quercetin fisetin
Quercetin 0.50
0.50 1.0 1 Peptide composition Hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine
Dipeptide - D-glutamyl-tryptophan Hexapeptide
Dipeptide 0.01
0.01 0.02 2 Composition for the base of a cosmetic composition - emulsifiers, co-emulsifiers, emollients, humectants, thickeners Olivem 1000: cetearyl and sorbitan olivate
Glycerol
Caprylic triglycerides
Squalane
Guar gum Cetearyl Olivate (and) Sorbitan Olivate
Glycerin
Caprylic/Capric Triglyceride
Squalane
Cyamopsis Tetragonoloba (Guar) Gum 5.00
5.00
7.00
2.00
1.50 20.50 3 Preservatives Anisic acid and polylysine p-Anisic Acid, Polylysine 1.2 1.20 4 Composition of stabilizers Cetearyl alcohol
1,2 - Hexanediol Cetearyl Alcohol
1,2-Hexanediol 1.50
0.30 1.80 5 Additional Ingredients Chelator - tetrasodium glutamate diacetate
Palmarosa essential oil
pH regulator citric acid Tetrasodium Glutamate Diacetate
Parfum Cymbopogon Martini Essential Oil*
Citric acid 0.15
0.01
0.01 0.17 7 Water Water Aqua rest

The combined use of a senolytic composition, a peptide composition, a composition of anti-inflammatory ingredients, as well as a composition of fatty oils and a composition of hyaluronic acids in the created cosmetic composition with anti-aging activity is justified by the properties of each of the components included in the composition of the claimed cosmetic composition.

One of the significant reasons for the aging of the body is considered to be the accumulation of old, or senescent cells, and the flow of “senescent” signals they generate, which spreads to other young cells of the body. A recent study showed that transplanting senescent cells into young mice accelerates aging. On the contrary, selective destruction of senescent cells using senolytic drugs improves the health of mice and prolongs their life. Moreover, clinical trials of senolytics for the treatment of aging diseases in humans are already beginning. Some of the cells inhabiting our body stop dividing and renewing with age, “aging” - this is how senescent cells appear.

Chromosomes end with the sequence TTAGGG, repeated thousands of times in telomeres. Loss of terminal DNA makes endless cell proliferation impossible. Shortening the telomeres of chromosomes to a certain size induces cellular aging processes; the cell stops dividing and grows old. The number of cell divisions completed before the proliferation block is “turned on” varies among different cells. Usually this is from 30 to 100 divisions. There is scientific evidence to suggest that it is senescent cells that can provoke the development of tumors, senile neurodegeneration, and create atherosclerotic plaques that disrupt the blood supply to the brain, heart and other organs. These cells do not die in a timely manner and release their waste products. In addition, when blood circulation is impaired by an atherosclerotic plaque and the development of ischemia of the blood supplying tissue, oxidants are released, which further aggravates the situation.

Senolytics (English senolytics from senile - decrepit and lytic - lysing, destroying) is the conventional name for a class of drugs, natural and natural ingredients, the distinctive feature of which is the ability to selectively initiate the death of senescent cells. The claimed cosmetic composition contains quercetin phytosome with lecithin, fisetin with raspberry ketone, grape seed oil rich in resverotrol and procyanidin. One of the signs of a cell switching to the path of irreversible aging is derepression of the p16INK4a gene, which maintains the viability of senescent cells by preventing their apoptosis.

(Martin N., Beach D., Gil J. “Ageing as developmental decay: insights from p16(INK4a.).” (English) // Trends in molecular medicine. - 2014. - Vol. 20, no. 12. - P. 667-674.).

It has been proven that the removal of senescent p16Ink4a-positive cells can successfully slow down the progression of age-related disorders even at later stages of life.

(Baker D.J., Childs B.G., Durik M., Wijers M.E., Sieben C.J., Zhong J., Saltness R.A., Jeganathan K.B., Verzosa G.C., Pezeshki A., Khazaie K., Miller J.D., van Deursen J.M. “Naturally occurring p16(Ink4a )-positive cells shorten healthy lifespan." // Nature. - 2016. - Vol. 530, no. 7589. - P. 184-189.).

By removing senescent cells, senolytics trigger an “on demand” regeneration process, the purpose of which is to fill the resulting space with new cells.

(Kaestner L., Bogdanova A. “Regulation of red cell life-span, erythropoiesis, senescence, and clearance.” // Frontiers in physiology. - 2014. - Vol. 5. - P. 269).

Thus, the tissue is rejuvenated. Most importantly, research into the effects of senolytics over the past five years has shown that drugs tested in animals and humans can actually work.

The study results, published in the journal Cellular and Molecular LifeSciences, advance current understanding of the effects of senolytics on aging cells.

(Pavel I. Deryabin, Alla N. Shatrova & Aleksandra V. Borodkina. “Apoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides.” Cellular and Molecular Life Sciences volume 78, pages. 7757-7776 (2021) .

It is known that polyphenols (senolytics) have many properties: antioxidant, anti-inflammatory, antitumor, anti-aging, cardioprotective.

(Ming Xu et al. “Senolytics improve physical function and increase life expectancy in old age.” Nature Medicine, August 2018).

Quercetin (chemical formula - 3,5,7,3'4' pentaoxyflavone) is an aglycone of rutin. Quercetin prevents the damaging effects of free radicals, inhibits the processes of lipid peroxidation of cell membranes and blood serum lipoproteins, and improves interstitial respiration. In addition, this flavonoid is a natural inhibitor of hyaluronidase, an enzyme that increases the permeability of the vascular wall; has a capillary protective effect (reduces the permeability and fragility of capillaries); improves microcirculation.

Quercetin is a promising agent for the treatment of diseases in many other areas of medicine, such as neurology, psychiatry, somnology, and oncology. Anxiolytic and antidepressant drugs have been shown in animal experiments

(Singh A, Naidu PS, Kulkarni SK. “Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.” Pharmacology 2003; 68:81-88.).

Existing studies in both animals and humans indicate that quercetin is a promising therapeutic agent in combination with several other chemotherapy drugs. Given the virtual absence of side effects (doses up to 1 g per day do not have a significant effect on hepatic and renal function, electrolyte levels and hemostasis), good tolerability and effectiveness, quercetin has good prospects in the treatment of many diseases, in studies for which it has demonstrated significant effectiveness.

(Chondrogianni N., Capeta S., Chinow I., Vassilatou K., Papassideri I., Gonos E.S. “Anti-aging and anti-aging effects of quercetin.” Exp Gerontol. October 2010).

Quercetin suppresses anti-apoptotic proteins of the BCL-2, BCL-xL family, that is, those that protect senescent cells from apoptosis.

(Chang J, Hsu Y, Kuo P, Kuo Y, Chiang L, Lin C. “Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line.” Life Sci. 2005;76: 1883-93.).

Quercetin activates pro-apoptotic signals, Bax and Bad.

(Chang J, Hsu Y, Kuo P, Kuo Y, Chiang L, Lin C. “Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line.” Life Sci. 2005;76: 1883-93).

Quercetin, a natural flavonoid, has anti-cancer effects without affecting normal cells. The mechanism of action, including dose-dependent anti-proliferative activity and the effect of induced apoptosis, biochemical and physicochemical studies was investigated. It can be concluded that quercetin directly binds to the BH3 domain of BCL-2 and BCL-xL proteins, thereby inhibiting their activity and promoting apoptosis of cancer cells.

(Alexandra Primikyri, Maria V Chatziathanasiadou, Evdoxia Karali, Eleftherios Kostaras, Michalis D Mantzaris, Eleftheria Hatzimichael, Jae-Sun Shin, Seung-Wook Chi, Evangelos Briasoulis, Evangelos Kolettas, Ioannis P Gerothanassis, Andreas G Tzakos. “Direct binding of Bcl -2 family proteins by quercetin triggers its pro-apoptotic activity." ACS Chem. Biol. 2014, 9, 12, 2737-2741.).

And these same proteins are responsible for blocking apoptosis in senescent cells.

(Chang J, Hsu Y, Kuo P, Kuo Y, Chiang L, Lin C. “Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line.” Life Sci. 2005; 76: 1883-93.).

The claimed cosmetic composition uses quercetin in a phytosome together with lecithin. Quercetin protects the skin from damage, including from ultraviolet radiation, toxic chemical compounds, has powerful antioxidant potential, and can reduce redness, itching and inflammation of damaged skin; phytosome restores skin barrier function, increasing hydration and reducing water loss. But the most important property is the senolytic effect on senile cells.

(Giada Maramaldi, Stefano Togni, Ivan Pagin, Luca Giacomelli, Roberta Cattaneo, Roberto Eggenhöffner, Samuele E Burastero. “Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study.” Indena S.p.A, Milan, Department of Surgical Sciences and Integrated Diagnostics, School of Medicine, Genova University, Genoa, Abich Srl, Verbania, San Raffaele Scientific Institute, Milan, Italy.)

The flavanol, epigallocatechin gallate, was used, which induces apoptosis of tumor cells and prevents cell growth by interacting with regulatory and signaling proteins of the cell cycle.

(Tarique Hussain, Bie Tan, Yulong Yin, Francois Blachier, Myrlene C. B. Tossou, and Najma Rahu, “Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?”,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 7432797, 9 pages, 2016.).

Procyanidin in the claimed cosmetic composition is contained in grape seed oil. Proanthocyanidins are also known as procyanidin, oligomeric proanthocyanidin, leukocyanidin, leukocyanidin and condensed tannins - a class of flavonoids that are powerful antioxidants. Procyanidin is a polymer chain of flavonoids such as catechin. Grapes (including grape seeds, skins, stems) are a rich source of procyanidin. The concentration of procyanidin in grapes reaches 1.2-2.5 g/kg (fresh grapes), 150-400 mg/liter (white wine) and 0.8-2.5 g/liter (red wine). Grape procyanidin is released by hydrolysis of catechin, epicatechin, epicatechin gallate and epigalocatechin. Procyanidin helps reduce levels of harmful oxidized forms of low-density lipoprotein (known as bad cholesterol). Proanthocyanidins reduce the rate of oxidation and transformation of lipoproteins into a similar form and increase the content of high molecular weight lipoproteins in the blood plasma. This factor helps reduce the risk of cardiovascular diseases. As a reducing agent, procyanidin is involved in the prevention of cancer of the gastrointestinal tract and internal organs. According to research, proanthocyanidins increase the time of platelet aggregation and blood clotting and can stimulate vasodilation, which leads to improved blood supply to the tissue. As ion chelators, grape proanthocyanidins affect the bioavailability of a number of toxic metals. A recent scientific study has shown that procyanidins promote weight loss and prevent the development of type 2 diabetes. That is why it is believed that dark chocolate has a positive effect on your figure. Dark types of chocolate contain large amounts of procyanidins.

(Dhanushka Gunawardena, Suresh Govindaraghavan, Gerald Münch, “Chapter 30 - Anti-Inflammatory Properties of Cinnamon Polyphenols and their Monomeric Precursors.” Polyphenols in Human Health and Disease Volume 1, 2014, Pages 409-425).

(Toshihiko Shoji, Tomisato Miura, “Chapter 104 - Apple Polyphenols in Cancer Prevention.” Polyphenols in Human Health and Disease Volume 2, 2014, Pages 1373-1383).

Fisetin is a natural pigment, dye that gives a beautiful golden hue. It was first discovered at the end of the 19th century, but active research into its beneficial properties began only recently. Chemically, fisetin is a plant polyphenol from the group of flavonoids (chemical formula - 7,3', 4'-flavon-3-ol; or 5-dihydroxyquercetin).

The effects of the natural dye fisetin in the fight against old age have been studied. The results of their study were published on September 29, 2018 in the journal EBioMedicine. It has been proven that the substance can extend life by about 10%. And Laura Niedernhofer, head of the Institute on the Biology of Aging and Metabolism at the University of Minnesota, who also studied the capabilities of this substance, writes: “Fisetin is a natural product that can selectively effectively kill senescent cells.”

In a recent study testing the senolytic activity of ten flavonoids, fisetin was most potent in reducing the number of senescent cells in mouse and human adipose tissue, while administration of fisetin to elderly mice restored tissue homeostasis, reduced age-related pathology, and increased mean and maximum lifespan.

(Yousefzadeh MJ et al. “Fisetin is a senotherapeutic that extends health and lifespan.” Ebiomedicine (2018) 36, 18-28).

The claimed cosmetic composition uses fisetin, a flavonoid isolated from Buxus sinica, which remodels and reduces adipose tissue, has an anti-inflammatory effect, is an antioxidant, and, most importantly, increases skin elasticity by 48% according to the manufacturer. Used in a composition with a solvent made from natural plant materials - propanediol and raspberry ketone.

Resveratrol is a senolytic no less significant than quercetin and fisetin. Resveratrol is contained in our cosmetic composition in grape seed oil. Of particular interest to researchers is the effect of resveratrol on the aging process of the skin. It has been shown that, due to its antioxidant properties, resveratrol reduces the content of reactive oxygen species in skin keratinocytes under the influence of ultraviolet irradiation and prevents damage and degenerative changes in the epidermis. The cosmetic depigmenting properties of resveratrol are no less important. By inhibiting the expression of tyrosinase, a key enzyme in melanogenesis, resveratrol reduces melanin synthesis and prevents skin hyperpigmentation and photoaging. Resveratrol has a dose-dependent inhibitory effect on elastase, hyaluronidase and collagenase, the activity of which increases under the influence of ultraviolet radiation, inflammation, and with age. Reducing the degradation of collagen, elastin and hyaluronic acid prevents age-related changes in the skin, accompanied by a loss of elasticity, firmness and moisture.

(Dan-Dan Zhou, Min Luo, Si-Yu Huang, Adila Saimaiti, Ao Shang, Ren-You Gan, Hua-Bin Li. “Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases.” Oxidative Medicine and Cellular Longevity / 2021).

Pepper senolytic: Piperlongumine is an ingredient from Indian hot long pepper (Pippali). It has anti-cancer and anti-aging properties. Piperlongumine is able to stop the production of a special enzyme in the body. This enzyme is found in large quantities in tumors. Using X-ray crystallography, the reconstructed molecular structures showed how piperlongumine was transformed after entering the body. It is transformed into an active agent that suppresses the activity of the GSTP1 gene. This gene is associated with the production of an enzyme that is present in tumors. Thus, scientists have proven the properties of pepper, popular in Indian cooking.

Peptides:

Dipeptide D-glutamyl-tryptophan regulates the processes of repair and regeneration of the skin through the production of information molecules that restore normal intercellular interaction and cell activation to launch the mechanism of natural skin renewal. Activates the restoration of cellular communications, activates the function of fibroblasts, collagen synthesis, enhances the production of IL-2 and the expression of its receptor by lymphocytes, enhances their proliferative activity. The dipeptide stimulates the T-cell component of the immune system, activates macrophages and natural killer cells, and enhances the spontaneous production of IL-1β.

Tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine hexapeptide restores skin microcirculation and gently cares for the skin. Increases the speed of blood flow in microcapillaries, normalizes and regulates vascular tone, restores blood flow in previously static vessels, increases the number of functioning microvessels, and improves blood outflow.

IL-1 polypeptide: the skin today is a highly organized organ of the immune system, which has the necessary composition of immunocompetent cells that cooperate with each other both with the help of complementary structures on their surface and with the participation of immunoregulatory cytokines, which in turn are signaling and information molecules . Such an organization allows the skin to participate both in the immune reactions of the whole organism and to carry out some immunological processes independently, on the spot - we are talking about self-renewal of tissue due to the skin’s own stem cells. Skripkin Yu.K., Lezvinskaya E.M. Skin is an organ of the immune system // Vest. dermatol. and venerol. - 1989. - No. 10. - With. 14-18.; Zimina I.V., Lopukhin Yu.M. Skin as an immune organ: cellular elements and cytokines // Immunology. - 1994. - No. 1. - With. 8-13.

The division of the skin's own stem cells is activated when the polypeptide acts on the cells of the epidermis and dermis. To do this, the polypeptide binds to keratinocyte receptors and triggers a cascade of other cytokines and cell growth factors.

Anti-inflammatory ingredients:

Anti-inflammatory boswellic acids from purified frankincense resin. The composition includes 6 acids obtained from Boswellia. Boswellic acids block the “arachidonic acid cascade” by inhibiting 5-lipoxygenase activity. Test Results: Boswellia extract significantly inhibits the activity of 5-lipoxygenase, acting with greater efficiency than NDGA and acids, and at the same level as glycyrrhetinic acid.

M.Z. Siddiqui. "Boswellia Serrata, A Potential Anti-Inflammatory Agent: A Review." Indian J Pharm Sci. 2011 May-Jun; 73(3): 255-261.

Aloe vera gel is extracted from the plant of the same name. In this application, ECO gel is used for the care of all skin types; it is a powerful moisturizer and anti-inflammatory component. Indications for use: any violation of the integrity of the skin, inflammation, acne, dehydrated skin, irritation, peeling of the skin. For damage caused by thermal or sunburn, aloe vera helps lower the temperature of the burned area and promotes regeneration. For insect bites, it relieves itching and reduces pain. For eczema, scabies and psoriasis, it soothes the skin and helps reduce the affected area.

Barpull G is a natural film-forming complex consisting of microalgae, sea water and natural polysaccharides. Rhodellaviolacea, a red microalgae measuring 10 picometers in size, is common in North America, Europe and Asia and is red, blue or purple in color and rich in polysaccharides and phospholipids. Barpull G is created using biotechnology and does not contain GMOs.

AcquaCell is an instant moisturizing ingredient. Aquacel is a natural complex of watermelon rind extract, lentil extracts and unripe and ripe apple peels, placed in a specially selected system for delivering active components to the skin. Aquacel contains the same key elements as NMF, the skin's natural hydration mechanism found in the stratum corneum.

Fixed oils:

Passion fruit (passiflora) oil contains: Vitamins C, A, potassium, phosphorus and other trace elements, fatty acids (linoleic, oleic, palmitic, lauric, margaroleic, stearic, margaric, myristic, palmitoleic, etc.). Passionflower oil is rich in antioxidant substances, which means it perfectly softens, nourishes and moisturizes the skin, soothes the skin and relieves irritation. Often used in massage mixtures, it has a relaxing effect, relieves tension and spasms, and has antibacterial properties. The oil is absorbed well and quickly by the skin, without leaving a feeling of heaviness or clogged pores.

Apricot kernel oil. Ingredients: polyunsaturated and monounsaturated fatty acids, vitamins A, C, group B, phospholipids, minerals, pantothenic acid. Light vegetable oil is often used in moisturizing and nourishing products, as well as in eyelid skin care cosmetics. Indispensable for sensitive, aging and baby skin, helps restore, soften and regenerate the skin.

Evening primrose oil. Oil with pronounced softening and moisturizing properties. It gently soothes, smoothes the skin, brightens it and eliminates age spots. It has a good effect on dry, irritated and flaky skin, removes redness and irritation, and strengthens the walls of blood vessels. Prevents premature aging.

Macadamia nut oil. Luxurious oil with a rich composition close in components to the fats of marine mammals. Absorbs very well, instantly softens the skin, eliminates peeling and irritation, makes the skin softer and more delicate. The oil has valuable cosmetic properties, which are due to its unique composition, close to oils extracted from marine animals. It has good softening and nourishing properties, while being instantly absorbed and distributed over the skin without problems. Restores skin, has antioxidant properties. Especially useful for aging and dry, irritated skin. Intolerance to this oil practically does not occur.

Camellia oil. Rich in composition, but light, the oil has many beneficial properties. It penetrates deeply into the skin, reduces moisture loss and enhances the protective functions of the epidermis. It has a good effect on dehydrated and dry skin types, giving a feeling of elasticity for a long time. Because the oil stimulates procollagen production, it is a common ingredient in anti-aging creams and oil blends. Camellia oil also reduces pigmentation, smoothes fine wrinkles, and has a tonic effect. In the care of delicate skin around the eyes, it combats dark circles and gently nourishes.

Grape seed oil. The most powerful natural antioxidant, free radical blocker due to the content of two natural senolytics - resveratrol and procyanidin.

Amaranth oil is high in squalene. The oil contains vitamin E in a rare tocotrienol form and squalene, a rare substance found in human subcutaneous fat, which improves the penetration of oil into the skin and activates regenerative processes. Ingredients: polyunsaturated fatty acids (such as arachidonic, stearic, linoleic, palmitic, linolenic, oleic), squalene, vitamins B and D, E, A, phytosterols, chlorophyll, bile acids, choline and alcohols. The oil is quickly absorbed and digested, does not cause allergic reactions, and creates an antibacterial barrier. The presence of squalene in the composition also makes it possible to activate regenerative processes, so the oil is actively used in the treatment of skin damage, as well as ulcers, eczema, psoriasis and other skin diseases.

Hyaluronic acids:

The cosmetic composition uses a combination of hyaluronic acids of different molecular weights.

Low molecular weight hyaluronan has a molecular weight of 150 - 1300 kDa. Other characteristics: quickly dissolves in water, penetrates well into the skin, has high biological activity, which significantly increases hydration, improves skin texture, and reduces sebum production. Effects are observed after two weeks of use and maximum effect after 2 months. Increases the activity of β-glucocerebrosidase, which is an important enzyme for the formation of lipids in the stratum corneum, which improves the condition of the transepidermal skin barrier and releases ceramides from their glycosyl precursors.

Low molecular weight hyaluronan can be used, for example, by the company Kontipro Rus, under the trade name HiSilk -

https://contipro.ru/#aa https://contipro.ru/images/AA.pdf.

Hyaluronic acid is a product of hydrolytic cleavage of high molecular weight hyaluronic acid with a molecular weight of 10-150 kDa, this hyaluronic acid is also obtained using biotechnological, recombinant synthesis, and has high biological activity. Proven skin penetration in clinical trials. Stimulates the synthesis of collagen and its own hyaluronic acid. Supports desquamation (sloughing) of the epidermis. Fights epidermal atrophy, increases the thickness of the epidermis, and has a moisturizing effect. For example, HiAktiv from the company Kontipro Rus - https://contipro.ru/#aa.

The third type of hyaluronic acid is hyaluronic acid oligomers: a mixture of hyaluronic acid oligomers - hyaluronic acid oligosaccharides that penetrate deeply into the skin. Properties: molecular weight < 5 kDa, dissolves faster in water, penetrates easier, better and deeper into the skin, has high biological activity, stimulates the synthesis of its own hyaluronic acid, expresses the hyaluronan synthase gene. The result is a reduction in wrinkles and an increase in elasticity, a decrease in the level of pro-inflammatory cytokines, the maintenance of angiogenesis (the growth of new microcapillaries in the dermis and the disappearance of old ones), a pronounced nutritional effect, and also a calming effect, and erythema decreases.

And the fourth is hyaluronic acid with a pronounced whitening effect. Consists of a natural derivative of a-linolenic and hyaluronic acids. Properties: energy production, antioxidant, anti-inflammatory. The compound uses low molecular weight hyaluronic acid, with a molecular weight of 10-15 kDa, penetrates deep into the skin and skin cells, transfers α-linolenic acid to the target - tyrosinase in melanocytes, protects α-linolenic acid from breakdown.

The combined use of hyaluronic acids with molecular weights: from < 5 kDa to 1300 kDa in a joint study shows results - they stimulate cell proliferation, have the properties of standard hyaluronic acid, first of all, significant hydration of the skin is achieved and the creation of a moisture depot in the epidermis, improves barrier function skin and hydration. This result is also confirmed in the study: (Gürkan Kaya, Christian Tran, Olivier Sorg, Raymonde Hotz, Denise Grand, Pierre Carraux, Liliane Didierjean, Ivan Stamenkovic, Jean-Hilaire Saurat “Hyaluronate Fragments Reverse Skin Atrophy by a CD44-Dependent Mechanism” Published: December 19, 2006).

Preservatives:

Anisic acid and polylysine. Acts as a preservative and is used in the examples given. For example, it can be used - EPSAN® - a preservation system developed on the basis of natural anisic acid and polylysine, which have antimicrobial effectiveness against fungi, yeast, bacteria, which makes it universal for use in nutraceuticals and cosmetics. ε-Polylysine is a natural homopolymer of L-lysine with a degree of polymerization of 25-35 with a molecular weight of about 5000, obtained through a fermentation process. Blocks NF-kB communication with DNA. Sodium Anisate is a salt of anisic acid with masking properties and fungicidal activity. Easily dissolves in water, decomposes into lysine and anisic acid and is completely absorbed; for a preservative effect in the composition of a cosmetic product, it is attached to the cell membrane of the microbe, damaging its structure, which leads to rupture of the intracellular lysosomal membrane, which stimulates microorganisms to autolysis (decomposition, decay) , thus causing the death of the bacterial cell.

Food preservatives: the use of which is permitted by ecostandards. Sodium benzoate, together with potassium sorbate and a preservative action enhancer - 1,2 hexanediol, is used in this composition.

Three groups of preservatives can be distinguished, which are used in option 1 and option 2. A specialist in this field understands that these are interchangeable preservatives and they can be combined with each other to enhance the effect and a greater breadth of coverage of microorganisms.

- salts of organic acids - sodium benzoate (Sodium Benzoate) and potassium benzoate (Potassium Benzoate).

- food preservatives (Potassium Sorbate, Calcium Sorbate, Sodium Sorbate),

- organic acids - benzoic acid, lactic acid and salicylic acid.

Potassium sorbate is a food preservative used to preserve creams, shampoos, tonics and other cosmetic products. The input percentage is 0.5% by weight of the product. Let's dissolve well in water and ready-made emulsions. To enhance preservative properties, it is recommended to use it together with sodium benzoate.

Sodium benzoate - prevents the appearance of molds and yeasts, slows down oxidative reactions, and also suppresses the activity of enzymes that destroy fats and starch. It is used not only in cosmetic products, but also in the food industry to preserve meat, fish, margarine, mayonnaise, ketchup, and carbonated drinks. Since sodium benzoate is not very effective against bacteria, it can be combined with potassium sorbate or lactic acid. The maximum dosage of sodium benzoate is 0.5%. It should be introduced into the aqueous phase or at the end of the preparation of the cosmetic composition. Unlike many preservatives, sodium benzoate does not lose its properties when heated and in an acidic environment. It is possible to use other food preservatives or natural plant extracts.

The main moisturizers and softeners in cosmetic compositions are hyaluronic acids, glycerin, aloe vera gel or juice.

Stabilizers:

Fatty oil stabilizers include: sunflower oil with rosemary extract (for example, Amyox) and a mixture of different forms of vitamin E (for example, Tocobiol C).

Amiox ER - Amiox protecting concentrate for cosmetic products. 100% natural rosemary extract in organic sunflower oil, concentrated and standardized for carnosic acid and carnosol. It is a highly effective natural antioxidant, the best natural alternative to conventional synthetic antioxidants for protecting lipophilic ingredients and cosmetic formulations from oxidation. Advantages:

1. Natural alternative to synthetic antioxidants,

2. Efficiency equivalent to butylated hydroxytoluene BHT.

3. Eco-friendly ingredient based on plant-based, natural ingredients.

Various forms of vitamin E are added to the oil phase to stabilize it (especially for vegetable oils) and heated to 80°C, but for a short time.

Tocobiol C (Composition according to INCI Tocobiol C, according to CAS it is a composition of α-Tocopherol, β-Tocopherol, γ-Tocopherol, δ-Tocopherol, β-Sitosterol, Squalene, Glyceryl Linolenate) - a liquid concentrated mixture of tocopherols, sterols, natural squalene and monoglycerides. Tocobiol is used as a base antioxidant to protect formulations, but has a number of additional benefits, such as providing skin hydration, acting as an anti-aging agent by blocking free radicals, and providing additional protection to the skin from harmful UV rays. Has an anti-inflammatory effect.

Cetearyl alcohol or cetearyl alcohol has the following properties: it is a thickener and stabilizer of the viscosity of the oil in water system, acts as a co-emulsifier (prevents the separation of components), softens the skin, tightens pores, does not irritate, disinfects, retains moisture in the skin, forms a film, gives the skin velvety, silky, emulsion softener and stabilizer, emollient, improves the consistency of anhydrous products.

1,2-Hexanediol - 1,2-Hexanediol. A multifunctional auxiliary ingredient in skin care cosmetics: it makes the formula soft and pleasant to use, acts as a moisturizing and softening component, dissolves other substances and further enhances the antimicrobial properties of preservatives.

Cosmetic composition for the base of a cosmetic composition: emulsifiers, co-emulsifiers, thickeners, humectants, emollients:

Emulsifiers:

Lamellar emulsifier Olivem 1000. Olivem 1000 (Cetearyl Olivate, Sorbitan Olivate) is a natural vegetable emulsifier from olive. Suitable for oil in water emulsions, i.e. for products with a leading aqueous phase. Olive oil is a storehouse of vitamins, antioxidants and polyunsaturated fatty acids, of which it consists almost entirely. Oleic acid, which is part of the emulsifier, breaks down harmful cholesterol in the body, while this does not affect the content of its beneficial variety, strengthens the walls of blood vessels, making them more elastic. Linoleic acid promotes rapid wound healing and accelerates regeneration processes. Vitamins A, D, E and K improve skin turgor (elasticity), protect against negative environmental factors, help slow down the aging process, improve blood supply to tissues, and stimulate metabolic processes.

All the properties inherent in olive oil are preserved in the Olivem 1000 emulsifier, which, thanks to its special structure, forms a very stable, separation-resistant emulsion by creating “liquid crystals” compatible with the structure of the skin, similar to the lipids of the upper layer.

The emulsifier is able to penetrate into the deep layers of the skin and integrate other beneficial ingredients into them, so Olivem1000 leaves the skin with an excellent light feeling of softness and hydration, restores and maintains the integrity of the skin barrier.

The second emulsifier is Pufos Alpha-gel (α-gel), PUREPHOS α is a gel lamellar structure formed in an aqueous medium by amphiphilic molecules of long-chain alkyl monophosphate (with the number of carbon atoms in the chain C = 16), processed using a special technology and neutralized with L-arginine (C16L-Arg). C16L-Arg molecules have a structure similar in structure to the structure of natural phospholipids of cell membranes (lecithins), consist of the same or similar structural units, and, like lecithins, aggregate in an aqueous environment, forming bilayer structures.

The use of PUREPHOS α α-gel in cosmetic formulations has an advantage because cosmetics based on bilayer lipid structures, in particular α-gels, are very comfortable for the skin. PUREPHOS α, when neutralized with L-Arginine, forms an α-gel - transparent, smooth, non-sticky, with a pleasant delicate texture and excellent distribution over the skin. Cosmetics using this α-gel as a base bring a feeling of freshness when applied to the skin.

Co-emulsifiers, thickeners, humectants, emollients:

Caprylic Triglycerides: Esters of glycerol with caprylic and capric acids, natural softeners derived from coconut oil. Colorless transparent oily liquid. Insoluble in water, miscible with oils. Softens the skin without leaving a heavy greasy feeling. They have good moisturizing ability, preventing transepidermal water loss. Eliminate the unpleasant feeling of tightness and dryness of the skin. They replenish the lack of lipids in the intercellular cement and saturate the skin with fatty components. Are not comedogenic. Enhancers.

Squalane is used in option 2. Emollient, humectant, squalane from sugar cane. Squalane is one of the best emollients used in cosmetics due to its stability and moisturizing properties. The precursor of squalane, squalene, is involved in the formation of the lipid barrier and is naturally present in human skin (12-13%), prevents skin moisture loss, normalizes skin respiration, resists premature aging, has high penetrating ability, does not leave behind a feeling of greasy, provides pleasant tactile sensations, indicated for dry, dehydrated skin, has a protective function, does not allow moisture to evaporate from the surface of the skin. The level of its content in the skin rapidly decreases in women after 30. It is synthesized by the human sebaceous glands, but with age its production decreases and is not comedogenic. Absolutely harmless, does not cause reactions on the skin and mucous membranes. The main difference between sugar squalane and squalane obtained from other sources, in addition to low cost, commercial availability, high composition stability, and its repeatability from batch to batch, is the low content of impurities and the certainty of their composition - these are saturated hydrocarbons with a carbon chain length of C15 and C45.

Glycerin: humectant, softener, co-emulsifier, stabilizer, viscosity regulator. Glycerin is a trihydric alcohol. This means that its chemical formula includes three water molecules. Due to its special molecular structure and high hygroscopicity (the ability to attract water), glycerin is successfully used in cosmetics as an active moisturizing ingredient. In its effect on the skin, glycerin is very close to hyaluronic acid.

Guar gum. Natural polysaccharide. Obtained from guar or Cyamopsis quadruptera. Guar beans have a large secondary endosperm containing galactomannans, a substance that forms a gel in water. The composition includes polymers common to all plant resins, consisting of D-mannose and D-galactose, 5-7% protein and a small amount of enzymes. High quality guar gum is soluble in cold water, forming an opaque viscous colloidal solution at a concentration of about 1%. The higher the temperature of the solution, the faster the gum swells. Guar gum is declared as a food additive E412. It is widely used in the food industry as a consistency stabilizer, thickener, and binding agent in jams, marmalades, cheeses, fermented milk and other products.

Xanthan gum. Xanthan gum is a fine-grained powder the color of baked milk. It is obtained by fermentation of microorganisms that live on plants of the cabbage family. Xanthan gum or xanthan gum is an absolutely safe and environmentally friendly product. Xanthan gum is most often used as a thickener and stabilizer. Even at a minimum concentration, a viscous, stable solution is obtained. Xanthan dissolves in cold and warm water, ethyl alcohol and glycerin. At the same time, emulsions using this gum are thicker at rest, and when stirred they become more liquid. To improve the properties of the emulsion, you can combine xanthan with guar or carob gum, as well as other thickeners. Xanthan gum is useful to add to daytime and facial protection products, as it creates a thin film on the skin and does not allow moisture to evaporate. Some anti-inflammatory effects are also noted.

Other Ingredients (odor absorbent, fragrance, chelator, pH regulator):

Odor absorber for fatty oils - Sinodor - citronellyl methyl crotonate, an active that masks the odors of cosmetic formulations, especially the fatty phase. It is an odorless derivative of natural citronellol and has two actions:

- it 'captures' unpleasant odors such as amines and thiols,

- it is digested by bacteria or skin enzymes, releasing citronellol.

Fragrance: as a flavoring agent, a specially developed aroma is used by perfumers based on natural essential oils, or they generally use aroma in individual cosmetic compositions, because they contain natural fatty oils that have their own aroma, depending on what raw materials the fatty oil is prepared from. A cosmetic composition on a neutral basis, containing no fatty oils and without its own aroma (which does not smell of anything) can be scented with any useful essential oil you like, for example, palmarosa essential oil. Palmarosa essential oil belongs to the class of tonic aromas and aphrodisiacs, to the cereal family. Smell: floral with a pink tint. Ingredients: limonene, geranyl acetate, geraniol, linalool, myrcene. Palmarosa oil is suitable for any skin type, helps cope with acne and other skin diseases, regulates the functioning of the sebaceous glands, which makes life much easier for those with oily skin, but is not useless for dry skin - it activates the skin’s defenses and normalizes its activity . Can be used with sensitive skin, improves the condition of dermatitis, eczema, and dry skin prone to irritation. It refreshes, tones, fights age-related changes, is an excellent organic deodorant, has a beneficial effect on blood vessels and has good regeneration potential. There is evidence that the aroma of palmarosa essential oil can improve mood on gloomy, rainy autumn days.

Chelator: Tetrasodium Glutamate Diacetate of natural origin, for example, under the brand name Dissolvin, a water softener, a chelator (chelating agent) is a substance that can react with metal ions, resulting in the formation of chelates - compounds that are not able to react with other substances in the cosmetic product. Chelating agents neutralize the ability of metal ions to react with other components of a cosmetic product. Chelators create a new substance with metal ions - a chelate, which is absolutely harmless and inert. Hence the properties of chelators, which: stabilize the system as a whole, prevent some assets from precipitating, prevent the decomposition of components and oxidation of oils, increase the shelf life of a cosmetic product, and have additional cosmetic properties (this only applies to natural chelators).

pH regulator - citric acid: adjusting the pH of a cosmetic product is necessary to create a comfortable feeling on the skin surface when using the product and not affect the natural pH level of the skin in the area of application, so that there is no irritation on the skin. Therefore, it is necessary to strive to endow a cosmetic product with a physiological pH - that is, an indicator as close as possible to the own pH of a certain area of the body, especially on the skin of the face and around the eyes. This is done by measuring the pH of the created cosmetic product immediately after the cooking process and adjusting it if necessary. In the claimed cosmetic compositions, this is bringing the pH of cosmetic compositions for the face, neck and décolleté to 5.5-6.0 and cosmetic compositions around the eyes to 5.5 using citric acid.

The cosmetic compositions of this invention are manufactured in a manner known to one skilled in the art, in accordance with established operating procedures for the manufacture of these products. These methods are standard and comply with GOST 31460-2012.

Example 1.

This example describes a typical method for manufacturing a cosmetic composition according to the stated recipes.

1. Purified water is loaded into a clean and disinfected cooking apparatus. Turn on the heating and stirrer of the cooking apparatus (30-40 rpm).

2. Add water-soluble components, chelator, solvent, thickener, humectant, depending on the formulation, into the water, namely: tetrasodium glutamate diacetate, guar gum, glycerin, 1,2-hexanediol.

3. Stir with a stirrer (30-40 rpm) until a clear solution is completely formed (at least 5-10 minutes).

4. Turn on the heating and stirrer of the cooking apparatus. Heat the water, with constant stirring, to a temperature of (70-75) ° C.

5. The components of the fat phase are loaded into the melting apparatus, depending on the recipe: fatty oils, emulsifier, co-emulsifier, emollient, stabilizers, namely: cetearyl and sorbitan olivate, cetearyl alcohol, caprylic triglycerides, passionflower oil, apricot kernel oil, primrose oil evening, macadamia oil, camellia oil, grape seed oil, amaranth oil, sunflower oil, rosemary extract, squalane.

6. Turn on the heating of the melting apparatus. The fat phase is heated in a melting apparatus, with stirring, to a temperature of (70-75) ° C and the formation of a homogeneous, transparent melt. Load the molten fat phase, under vacuum, into the cooking apparatus.

7. Mix the fat phase (temperature 70-75°C) and the aqueous phase (temperature 70-75°C) with a stirrer (30-40 rpm) for 3-5 minutes.

8. Turn on the homogenizer of the cooking apparatus and homogenize the water-fat mixture with the mixer running (30-40 rpm) for 10-15 minutes.

9. Turn on the cooling system of the cooking apparatus. Cool the mass in the cooker, with continuous stirring (30-40 rpm), to a temperature of 35°C.

10. At a temperature of (30-35) ° C and continuous stirring, sequentially load the active ingredients and preservatives into the cooker depending on the recipe at intervals of 5-6 minutes, namely: fisetin, quercetin, boswellic acids from purified frankincense resin, juice aloe vera, hyaluronic acid complex (hyaluronic acid (molecular weight 10-150 kDa), hyaluronic acid (mol. weight 150-1300 kDa), hyaluronic acid oligomers (mol. weight < 5 kDa), hyaluronic acid with linolenic acid), anisic acid and polylysine, citronellyl methyl crotonate, various forms of vitamin E (α-tocopherol and/or β-tocopherol and/or γ-tocopherol and/or δ-tocopherol), and/or β-sitosterol and/or squalene , and/or glyceryl linolenate.

11. The peptide complex is introduced: dipeptide (D-glutamyl-tryptophan) and/or (tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine hexapeptide), and/or polypeptide (IL-1) after cooling the mass of the cosmetic composition to 25°C , having previously dissolved the peptides in water.

12. Mix the mass of the cosmetic composition after introducing the peptides to ensure uniform distribution of the peptides.

13. If necessary, add a solution of citric acid to adjust the pH.

14. Stir the mass of the cosmetic composition (15-20 rpm) for 15-20 minutes. If necessary, homogenize the mass again. The cosmetic composition is evacuated (-0.6 Ati) for 20 minutes.

15. Relieve the vacuum. Turn off the mixer, take a sample of the finished product for the laboratory, in order to study stability, microbiology, etc. After receiving a positive conclusion from the laboratory, the mass is unloaded from the cooking apparatus and packaged.

Example 2.

Clinical application of a cosmetic composition with formulation No. 1: this example solves the problem of creating evidence of the effectiveness of a cosmetic composition for enhancing blood microcirculation through the smallest capillaries of blood vessels.

The cosmetic composition was used on the face, neck and décolleté area by 10 female volunteers for two months. When analyzing the degree of effectiveness of the Doppler indicator, which reflects blood microcirculation through the capillaries in the skin, before and after applying a cosmetic composition for the face, neck and décolleté, it was found that the microcirculation indicator significantly increased by 1/3 compared to the initial value (see Fig. 1 ) In Figure 1, the x-axis is the weeks of research, and the y-axis is the conventional measured units of the state of the microvasculature of the skin. This has been shown to indicate a high level of increased blood flow in the skin. The Doplerometry (microcirculation) indicator was assessed using a laser analyzer “LAKK-OP” (Russia), based on the principle of laser fluorimetry.

Conclusion: the indicator of the state of the microcirculatory bed of the skin has changed, statistically significantly increased by 32.4%, that is, the trophic function of the skin, the speed of blood flow and the supply of oxygen and nutrients to the skin have improved by this amount, the function of the microcapillary endothelium, partially lost with age, has been restored, rejuvenating effect of cosmetic composition.

Example 3.

Clinical application of a cosmetic composition with formulation No. 2: in this example, the positive effect of a fatty cosmetic composition on improving the condition of aging skin in premenopause and menopause was proven, which was reflected by the measured parameters.

The cosmetic composition of formulation No. 2 was studied on 10 volunteers - women aged 50 to 64 years with obvious signs of age-related changes, twice a day for two months. The following measured parameters were assessed: moisture testing, elastometry, profilometry and Doppler measurements (the state of blood microcirculation through the capillaries). Skin moisture and elastometry indicators were determined using the Multi Skin Test Center® MC 750 device, manufactured by Courage + Khazaka electronic GmbH (Germany). The skin profilometry index was determined using a VISIOSCKAN VC 98 profilometer manufactured by Courage + Khazaka electronic GmbH (Germany). The Doppler indicator (the state of skin microcirculation) was studied using an ultrasonic Doppler continuous-pulse analyzer-monitor of intracranial and peripheral circulation “Angiodin-PK” (Russia). All studied parameters were measured before using the cosmetic composition, and two months after the start of using the cosmetic composition.

The results are expressed as a percentage of the initial state (the measured initial state is conventionally taken as the reference point, the percentage reflects only the changed average measurement value) the results are reflected in Table 1.

Table 1

Index % change Moisture testing + 5.2 Elastometry + 33.8 Profilometry - 6.3 Doppler + 24.2

Conclusion:

An increase in moisture metering, elastometry and, especially, Dopplerometry indicates increased metabolic processes, improved skin nutrition, increased oxygen flow into the skin and indicates the rejuvenating effect of the cosmetic composition. Negative profilometry data also confirm this conclusion, because they indicate a smoothing of the skin texture from the initial level, a reduction in wrinkles and other skin irregularities that occur with age.

Example 4.

Clinical application of cosmetic composition formulation No. 3.

Using this example, they proved the positive effect of the cosmetic composition of formulation No. 3 on improving the condition of the skin, which was reflected by the measured parameters.

The cosmetic composition of formulation No. 3 was studied on 20 volunteers - women aged 35 to 47 years with signs of age-related changes of varying severity, twice a day for eight weeks. The criteria for assessing effectiveness were the following indicators: moisture testing, elastometry, profilometry and Doppler measurements (the state of blood microcirculation through the capillaries). Skin moisture and elastometry indicators were determined using the Multi Skin Test Center® MC 750 device, manufactured by Courage + Khazaka electronic GmbH (Germany), before and after using the above mentioned cosmetic product for eight weeks. The skin profilometry index was determined using a VISIOSCKAN VC 98 profilometer manufactured by Courage + Khazaka electronic GmbH (Germany). The Doplerometry (microcirculation) indicator was assessed using a laser analyzer “LAKK-OP” (Russia), based on the principle of laser fluorimetry. The measuring capabilities of these devices are highly sensitive to changes in the studied indicators of the functional state of the skin.

The results are expressed as a percentage of the initial state (the measured initial state is conventionally taken as the reference point, the percentage reflects only the changed average measurement value) the results are reflected in Table 2.

table 2

Index % change Moisture testing + 8.2 Elastometry + 22.3 Profilometry - 7.4 Doppler + 43.9

Conclusion:

An increase in moisture metering, elastometry and, especially, Dopplerometry indicates increased metabolic processes, improved skin nutrition, increased oxygen flow into the skin and indicates the rejuvenating effect of the cosmetic composition. Negative profilometry data also confirm this conclusion, because they indicate a smoothing of the skin texture from the initial level, a reduction in wrinkles and other skin irregularities that occur with age.

Example 5.

Clinical application of cosmetic composition formulation No. 4.

This example demonstrated the strengthening of reparative processes in the skin after the use of a cosmetic composition. Since such a problem cannot be proven on intact smooth skin, we took a model on skin with acne (pimples).

A clinical trial of the cosmetic composition was conducted on 25 patients with moderate acne.

Materials and methods:

For clinical trials, a cosmetic composition of formulation No. 2 was used; when applied, at least 1 ml of the cosmetic composition was used on the face. the cosmetic composition was applied twice daily for four weeks.

The study included three control visits of patients, during which changes in the course of the acne disease were noted, the emergence of criteria for reducing the clinical manifestations of acne, and improvement of the condition were monitored, including attention to the appearance of new elements of acne. The results achieved were documented. Patients visited a dermatologist for study documentation before treatment, 2 weeks after treatment, and 4 weeks after treatment. In addition, patients were observed by a dermatologist, without photographs, during the first three days from the start of treatment, due to the temporary increase in inflammation characteristic of such therapy. It was due to this increase in inflammation that acne elements healed quickly with minimal scarring. Treatment evaluation was carried out on the basis of patient statements and dermatologist's assessment, and the treatment result was recorded photographically.

Tolerability was assessed by patients and a dermatologist: mediocre, satisfactory, good and very good.

Results:

1. Study patients:

This study included 15 female and 10 male patients. The average age was 25.3 years ± 7.2 years for women and 23.7 ± 8.3 years for men. The average age of acne onset is 17 years ± 6.7 years. In 41% of cases, no familial acne cases were noted. 40% of the subjects had previously received treatment for acne, 35% exclusively topical, 30% combined (per os and topical). In 20% of cases, this treatment was carried out after completion of a course of isotretinoin. The most frequently used drugs were erythromycin, benzoyl peroxide, topical adapalene, tetracyclines and per os isotretinoin.

In general, 86% of the subjects were patients with moderate acne, with a predominance of microcysts and comedones, and rarely with papulopustular rashes.

2. Those who passed the test:

No patients withdrew from the trial before completion.

3. Performance assessment:

3.1 The effectiveness of treatment according to the nature of the disappearance of pustular elements of acne.

The effectiveness of treatment according to the nature of the disappearance of pustular elements of acne is presented in Table 3.

The research data is shown in the diagram. The Y axis is the percentage of treatment effectiveness, the X axis is the time interval. This applies to both charts. (See Figures 2A, 2B).

Table 3.

Patients Through
2 days from the start of treatment One week after the start of treatment Two weeks from the start of treatment After 4 weeks from the start of treatment The appearance of relapses
assessed 2 weeks after cure 1. gain ++ ++++ ++++ No relapses 2. gain ++ ++++ ++++ No relapses 3. gain + ++++ ++++ No relapses 4. gain + ++ +++ Unit elements 5. Without changes ++ ++++ ++++ No relapses 6. Without changes +++ ++++ ++++ No relapses 7. gain + ++ +++ Unit elements 8. gain ++ +++ ++++ No relapses 9. Without changes + ++ +++ Unit
elements 10. Without changes + ++ +++ Unit elements eleven. Without changes + ++ +++ Unit elements 12. gain ++ ++ +++ No relapses 13. gain ++ +++ ++++ No relapses 14. gain + ++ +++ Unit elements 15. gain ++ +++ ++++ No relapses 16. gain + +++ ++++ No relapses 17. Without changes + ++ ++++ No relapses 18. Without changes + +++ ++++ No relapses 19. gain ++ +++ ++++ No relapses 20. gain ++ +++ +++ Unit elements 21. gain + ++ +++ Unit elements 22. gain ++ +++ ++++ No relapses 23. Without changes + +++ ++++ No relapses 24. Without changes + ++ +++ Unit elements 25. gain ++ ++++ ++++ No relapses

Criteria:

- lack of effect (acne progression),

+ low efficiency (disappearance of less than 20% of acne elements),

++ average effectiveness (disappearance of 50% of acne elements),

+++ high efficiency (disappearance of 80% of acne elements),

++++ 100% disappearance of acne elements.

Conclusion:

As a result of calculating the data obtained, it was revealed that after the first week of treatment with the cosmetic composition, the effectiveness of therapy was 35%, after two weeks of treatment - 72%, and after four weeks of treatment, the effectiveness was 92%. This indicates an increase in reparation, activation of cellular renewal of the skin, and the launch of an anti-aging effect while removing the appearance of acne elements.

3.2 Effectiveness on superficial inflammation. This study reflects the mechanism of action of peptides, increased microcirculation and increased inflammation, which leads to rapid resolution of inflammation, healing with minimal scarring and significant cellular renewal of the skin.

Efficacy based on the presence or absence of superficial inflammation is presented in Table 4.

The research data is shown in the diagram. The Y axis is the percentage of increased inflammation, the X axis is the time interval. See figure 2 (2C, 2D).

Table 4.

Patients Through
2 days from the start of treatment One week after the start of treatment Two weeks from the start of treatment After 4 weeks from the start of treatment 1. ++ +++ - - 2. ++ ++ - - 3. +++ ++ - - 4. +++ + - - 5. ++ ++ - - 6. ++ ++ - - 7. +++ +++ - - 8. +++ ++ - - 9. ++ ++ - - 10. ++ +++ + - eleven. ++ ++ - - 12. ++ +++ + - 13. +++ ++ - - 14. ++ ++ - - 15. +++ ++ + - 16. +++ + - - 17. ++ + - - 18. +++ + - - 19. +++ ++ + - 20. +++ ++ - - 21. ++ + - - 22. +++ ++ - - 23. +++ ++ + - 24. ++ + - - 25. +++ ++ - -

The following criteria were used:

- absence of inflammation,

+ mild inflammation (20%),

++ moderate inflammation (50%),

+++ pronounced inflammation (80%).

Conclusion:

as a result of calculating the data obtained, it was revealed that after two days of treatment, inflammation increased to 65.6%, after the first week of treatment, the increase in inflammation was 47.6%, after two weeks of treatment, only 4% of patients had signs of inflammation, and after four weeks of treatment, inflammation completely absent. This indicates a powerful immunomodulatory effect, activation of the cellular renewal process, enhancement of the healing effect, reparative processes and launch of a rejuvenating effect.

Example 6.

Clinical application of a cosmetic composition of formulation No. 5: in this example, the effectiveness of a cosmetic composition that was simpler than in examples 2,3,4,5 was confirmed, since it must be organoleptically, in terms of pH, acceptable for application to the skin around the eyes, eyelids, lips, do not cause redness and irritation in case of accidental contact with the mucous membrane of the eyes, lips, but with all active ingredients.

Cosmetic composition of formulation No. 5 was applied twice a day for eight weeks to areas of the facial skin with signs of age-related changes in ten women over the age of 30-35 years. The effectiveness of the cosmetic composition in reducing signs of skin aging was assessed using tests. The lower layers of the skin were assessed by ultrasound echography. The depth and location of wrinkles were assessed by profilometry. Skin elasticity and density were assessed using the vacuum method. The effectiveness of maintaining normal skin condition was assessed by transepidermal water loss (TWL). The results obtained at the eighth week of treatment are presented in Table 5 as a percentage change in the mean value to the baseline value (taken immediately before the start of treatment).

Table 5

Index Change Density of the epidermis and dermis + 10% Collagen and elastin density + 17% Elasticity + 12% TPV - 16% Wrinkles - 9%

Example 7.

Clinical application of cosmetic composition formulation No. 6.

Using an example, the effectiveness of a cosmetic composition for enhancing microcirculation has been proven to combat endothelial dysfunction that occurs with age, which at the age of more than 35 years leads to the gradual sclerosis of microcapillaries and their disappearance from participation in the blood supply to the skin.

Restoring microcirculation and lymphatic drainage is the main focus of anti-age therapy.

Purpose: to study the effect of a cosmetic composition on microcirculation of the skin of the face and around the eyes.

Materials and methods:

The study included 25 healthy women aged 35 to 54 years with clinical signs of biological skin aging (decreased turgor, skin elasticity, swelling of the lower eyelids, facial wrinkles of degree II-III). The study of the state of the microvasculature was carried out using an ultrasonic Doppler continuous-pulse analyzer-monitor of intracranial and peripheral circulation “Angiodin-PK” (Zelenograd, Russia). Blood flow in the skin microcirculation was assessed before application of the cosmetic composition (Figure 3A), 10 minutes after application (Figure 3B) and 15-20 minutes after application of the cosmetic composition (Figure 3C). This is processed by a special program, which is installed on the Word program on the computer and which calculates the microcirculation parameters measured by the device at a given measurement depth in the skin. The number of red blood cells passing through the cross-section of a microcirculation vessel in a certain unit of time is read. The indicator of the number of passing red blood cells is displayed in black, and by the contours of this curve one can judge the uniformity and unevenness of the blood flow. Uniform blood flow is characterized by smooth contours throughout the measured parameter.

A study of the initial level of blood flow in the skin of the lower eyelids showed that women over 35 years of age have a minimal level of capillary blood flow.

The appearance of black coloring, as well as an increase in its intensity, makes it possible to assess the change in the state of the microvasculature. A significant increase in microcirculation and the appearance of its uniformity are visible (the contours of black staining are visible after applying the cosmetic composition), which indicates the uniformity of the distribution of blood flow along the microcirculation capillaries in this area. The speed of blood flow significantly increased by almost 2 times; there was not only an increase in blood flow through the microcirculation vessels, but also an increase in outflow (See Fig. 3).

In patients with the use of a cosmetic composition, regression of eyelid swelling occurred, bruising and swelling under and around the eyes decreased, and the speed of microcirculation blood flow almost doubled from 40 to 70%. When analyzing the reduction of wrinkles subjectively by the doctor and patients, a reduction in wrinkles was found to be 35% assessed by the doctor and 30% by the patients. Reduction in swelling and dark circles when subjectively assessed by a doctor - 40% and by patients - 30%.

Conclusion:

Thus, an increase in microcirculation and an increase in blood flow speed, the appearance of uniformity of microcirculation against the background of the use of a cosmetic composition, has been proven.

Example 8.

Clinical application of a cosmetic composition with formulation No. 7.

Using this example, it was proven that the combined use of peptides (dipeptide and hexapeptide) in a cosmetic composition leads to a significant renewal of the cellular composition of the skin, as can be judged by the reduction of wrinkles, according to profilometry data and the reduction of puffiness and dark circles under the eyes.

In clinical trials, a cosmetic composition with two peptides - a hexapeptide and a dipeptide - was studied. The cosmetic composition was applied twice a day, morning and evening, for two months. The disappearance of wrinkles, puffiness and dark circles under the eyes was assessed (See Figure 4A, 4B, 4C).

External indicators were assessed by a doctor, patients, and using profilometry.

As a result of the analysis of objective results of profilometry (skin surface relief) under the influence of a cosmetic composition, it was found that this indicator, after using the cosmetic composition for 2 months, statistically significantly decreased by 8.1% from the original in arbitrary units.

When analyzing the reduction of wrinkles subjectively by the doctor and patients, a reduction in wrinkles was found to be 35% assessed by the doctor and 30-33% by the patients.

Reduction of swelling and dark circles when subjectively assessed by a doctor - 38% and by patients - 36 - 40%. The data is presented in Table 6.

Table 6.

Parameters studied in By patients Doctor Wrinkle reduction % 30-33 35 Reduction of swelling and dark circles % 36-40 38 The profilometry indicator decreased in conventional units 8.1

In comparison with its analogue, patent No. 2640915, the claimed invention includes a combination of different senolytics, both in pure form and as part of a fatty oil in combination with the action of a peptide composition. Quercetin is enclosed in a phytosome of lecithin (phosphotidylcholine), which can be incorporated into the cell membrane and participate in the restoration of this cell membrane.

In comparison with its analogue, patent No. 2743036, the claimed invention contains a cosmetic composition with a composition of senolytics and copeptides. The proposed peptides - dipeptide and hexapeptide do not match in the number of amino acids. The analog claims only peptides without senolytics.

In comparison with its analogue, patent No. 2753515, the claimed invention contains a more extensive anti-aging composition of the product. The composition described in the analog contains no senolytics.

In comparison with its analogue, patent No. 2679649, the invention includes a composition of senolytics. This analogue does not contain the composition of senolytics we offer in combination with a composition of peptides

Compared to the prototype, patent No. 2755201, the claimed invention uses other peptides with a unique mechanism of action in combination with senolytics in a cosmetic composition. We have four senolytics - quercetin, fisetin, resverotrol, procyanidin. Quercetin is placed in a phytosome of lecithin - phosphotidylcholine. Which significantly enhances its positive effect on the skin. The action of one of our peptides (dipeptide and/or polypeptide) is binding to a receptor that has homology with the glutamate receptor and the interleukin 1 beta receptor, triggering cellular renewal, enhancing repair, immunomodulatory effect on local, skin mucosal immunity, maintaining a cascade of cytokines to activate recovery loss of normal cellular composition with age and restoration of cellular interaction. The action of another peptide (hexapeptide) is interaction with receptors on the vascular wall of microcapillaries, on vascular endothelial cells, restoration and normalization of blood flow through the smallest vessels of microcirculation, increased blood flow speed, restoration and prevention of microcapillary endothelial dysfunction, increased trophic function, improved metabolism and lymphostimulating effect on lymphatic microcapillaries, active reduction of lymphangiomas. Strengthening lymph flow and outflow of excess interstitial fluid with toxins - waste products of cells. A powerful stress-protective effect on skin cells and protection from the effects of external, unfavorable environmental factors. The stress protector protects cells from damage and premature death, prevents endothelial dysfunction and prevents swelling. The claimed cosmetic composition uses 4 hyaluronic acids of different molecular weights, including those that penetrate the skin and have different effects, for example, whitening. The composition also includes seven fatty oils of the highest quality and powerful anti-inflammatory ingredients with proven properties.

The technical result of the claimed cosmetic composition with anti-aging activity is achieved due to the use of compositions of its constituent components. Due to this, the synergistic effect of each component in the composition is enhanced.

Component compositions used:

composition of senolytics,

peptide composition,

composition of anti-inflammatory ingredients,

composition of fatty oils,

composition of hyaluronic acids,

composition of stabilizers,

composition for the base of a cosmetic composition.

Moreover, each of the compositions of components claimed in this invention has a synergistic effect by enhancing the effect of each component on each other, while they are aimed at solving one problem, but it is precisely due to different points of application of action and influence on different mechanisms that they give an enhanced effect .

The composition of senolytics has, on the one hand, an enhancement of the action of two of the four senolytics used - quercetin and fisetin, which have a similar mechanism of action (fisetin is 5-dihydroxyquercetin, has a natural similarity of the molecule to quercetin and both enhance the effect of each other, acting on the same target), on the other hand, two other senolytics from grape seed oil - resveratrol and procyanidin - have a different mechanism of influence on senescent cells and act on other targets. And this combined effect of four senolytics provides the maximum significant effect on the removal of senescent (senescent) skin cells. Cosmetic compositions with four senolytics with multidirectional effects are more effective than cosmetic compositions with fewer senolytics.

The peptides used in the composition have different mechanisms of action and bind to different receptors, but each provide their own anti-aging effect and, acting together, also provide a synergistic effect and enhance each other. The dipeptide D-glutamyl-tryptophan binds to the receptors of keratinocytes and Langerhans cells and ensures effective cellular renewal and the launch of reparative ones. regenerative processes in the skin, at the site of application. IL-1 polypeptide binds to the receptors of keratinocytes, fibroblasts, skin macrophages, and also ensures the launch of reparative processes in the skin, ensures cellular renewal, and strengthens healing processes. The hexapeptide tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine affects the increase in blood flow rate, triggers blood flow in microcirculation vessels, which are already undergoing age-related degeneration, and restores the necessary blood flow in aging skin, thereby protecting skin cells from premature death, improving trophic function in skin, which provides an anti-aging effect not only in the skin, but also in nearby tissues, effectively combats endothelial dysfunction that occurs with age, and prevents the appearance and progression of age-related changes.

The remaining compositions of components also exhibit their synergistic effect due to the action of each component. Fatty oils have both a similar effect, common to all, this is a complex of vitamins, antioxidants, fatty acids, moisturizing, softening, protective effects, and each of them has its own distinctive positive properties for the skin. The combination of hyaluronic acids also works on different layers of the skin and enhances each other’s effect, due to the different molecular weight of hyaluronic acid.

Thus, the objective of the present invention, namely: the creation of a cosmetic composition with anti-aging activity to prevent aging and correct age-related changes in the skin, is achieved due to the fact that compositions of components of multidirectional action are used, which together form a single cosmetic composition with anti-aging activity to prevent aging and correction of age-related skin changes provide a difficult-to-achieve anti-aging effect. The invention also expands the arsenal of similar anti-aging agents.

Industrial applicability

The popularity of each of the claimed components, as well as all the examples given, confirm the industrial application of this invention.

Claims (5)

1. A cosmetic composition with anti-aging activity to prevent aging and correct age-related changes in the skin, characterized in that it contains a cosmetically or dermatopharmaceutically effective amount of an active component in the form of a senolytic composition, a peptide composition, a composition of anti-inflammatory ingredients, a composition of fatty oils, a composition of hyaluronic acids, etc. ingredients of the composition to create the basis of a cosmetic emulsion (cream) in the form of emulsifiers, co-emulsifiers, thickeners, moisturizers, emollients, as well as preservatives, stabilizers, chelators, pH regulators, fragrances or essential oils in the following ratios of components, wt. %: composition of senolytics,
which are used in combination: fisetin, quercetin, procyanidin and resveratrol
from 0.3 to 2.5 peptide composition,
which are used together as a hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine, and/or dipeptide - D-glutamyl-tryptophan, and/or polypeptide - IL-1 from 0.00505 to 0.11 composition of anti-inflammatory
ingredients that use aloe vera juice and/or
boswellic acids from purified frankincense resin
from 1.25 to 11.5 composition of fatty oils,
which are used in combination: passionflower oil, apricot kernel oil, evening primrose oil, macadamia oil, camellia oil, grape seed oil, amaranth oil
from 3.5 to 19 composition of hyaluronic acids,
which are used in total: hyaluronic acid with a molecular weight of 10-150 kDa, hyaluronic acid with a molecular weight of 150-1300 kDa, oligomers of hyaluronic acid with a molecular weight of <5 kDa, hyaluronic acid with linolenic acid from 0.3 to 0.71 composition of preservatives,
which are collectively used: sodium benzoate, and/or potassium sorbate, and/or benzyl alcohol or various combinations thereof and/or rosemary extract or a combination of anisic acid with polylysine from 0.7 to 1.2 composition of stabilizers, which together use:
sunflower oil with rosemary extract, a combination of different isoforms of vitamin E - α-tocopherol, and/or β-tocopherol, and/or γ-tocopherol, and/or δ-tocopherol, and/or β-sitosterol, and/or squalene, and /or glyceryl linolenate, and/or cetearyl alcohol, and/or 1,2 hexanediol from 1.55 to 2.05 composition for the base of a cosmetic composition, which is collectively used as:
emulsifier Puphos alfa, neutralizer arginine, Olivem 1000, caprylic triglycerides, glycerin, xanthan gum, guar gum, cetearyl alcohol, co-emulsifiers and/or emollients and/or thickeners and/or humectants from 5.5 to 10.45 additional ingredients, which are used in combination: PH regulator, chelator, odor absorber, fragrance or essential oil from 0.161 to 0.17 water rest (option 1) 2. A cosmetic composition with anti-aging activity to prevent aging and correct age-related changes in the skin, characterized in that it contains a cosmetically or dermatopharmaceutically effective amount of an active component in the form of a composition of senolytics, a composition of peptides, and other ingredients for the base of a cosmetic composition in the form of emulsifiers, co-emulsifiers, thickeners , humectants, emollients, preservatives, stabilizers in the following ratios of components, wt. %: composition of senolytics, which are used in combination
quercetin and fisetin
from 0.25 to 1.0 composition of peptides, which are used in combination
hexapeptide - tyrosyl-alanyl-glycyl-phenylalanyl-leucyl-arginine,
and/or dipeptide - D-glutamyl-tryptophan,
and/or polypeptide - IL-1 from 0.00505 to 0.02 composition of preservatives, which are used in combination:
sodium benzoate and potassium sorbate, and/or anisic acid and polylysine from 0.7 to 1.2 composition for the base of a cosmetic composition, which is collectively used as:
emulsifier Puphos alfa, neutralizer arginine, Olivem 1000, caprylic triglycerides, glycerin, xanthan gum, squalane, guar gum, cetiaryl alcohol and/or sorbitan olivate, co-emulsifiers and/or emollients and/or thickeners and/or humectants
from 14.5 to 20.5 composition of additional ingredients, which are used in combination:
chelators, fragrance, essential oils, pH regulators from 0.161 to 0.17 water
(option 2) rest 3. Application of a cosmetic composition according to claims. 1, 2 to prevent aging and correct age-related skin changes.