RU2752733C1 - Composition for producing cosmetics - Google Patents

Abstract

FIELD: cosmetics.

SUBSTANCE: invention relates to the cosmeceutical industry, namely to a composition exhibiting moisturising, sun-protective properties, activating collagen synthesis. A composition exhibiting moisturising, sun-protective properties, activating collagen synthesis, for preparing skin cosmetics, containing betulin and/or derivatives thereof selected from betulinic acid, betulonic acid, allobetulin, betulin diphosphate, lupeol, betulin diacetate, zinc oxide in form of nanoparticles with a size of 1 to 500 nm, vegetable oils and auxiliary substances, wherein a mixture of vegetable fatty oils and vegetable essential oils is used at a mass ratio of 100:1 to 5:1, wherein vegetable fatty oils selected from: sunflower oil, olive oil, rice oil, almond oil, castor oil, cocoa oil, peach oil, apricot oil, amaranth oil, mustard oil, corn oil, sea buckthorn oil, red palm oil, milk cap oil, pumpkin seed oil; and vegetable essential oils selected from: lavender oil, pine oil, geranium oil, thyme oil, eucalyptus oil, carnation oil, tea tree oil, anise oil, and auxiliary substances, at the following ratio of components, % wt.: betulin and/or derivatives thereof 0.10 to 20.00, zinc oxide particles 0.01 to 15.00, auxiliary substances 0.01 to 5.00, a mixture of vegetable fatty oils and vegetable essential oils up to 100.00.

EFFECT: described composition allows for activation of collagen synthesis and achievement of a high degree of moisturising, and exhibits effective sun-protective properties.

1 cl, 3 tbl, 22 ex

Description

The invention relates to the field of cosmeceutical industry, in particular, to the development of new means of prevention and correction of age-related skin changes (wrinkles, cellulite, age spots), for protection from UV radiation, containing biologically active substances of natural origin.

Low-toxic betulin and its derivatives (betulinic acid, betulonic acid, allobetulin, betulin diphosphate, lupeol, betulin diacetate) are obtained from birch bark and other plants with subsequent chemical modification. All of these compounds exhibit a wide spectrum of pharmacological activity and have shown good results as components of cosmetics.

It is known to use betulin and its derivatives in cosmetic and therapeutic and prophylactic agents for external use in the form of birch bark extract and dispersed in birch sap. [US 2019/0240134 A1 A skin care cosmetic composition]. However, the proposed compositions of the composition do not provide the stability of the cosmetic product due to the easy oxidizability of the components of birch sap. The disadvantages of the composition are the difficulty of obtaining birch sap (extraction in early spring within 1-2 weeks), its conservation, insufficient skin hydration, lack of a protective effect, and the difficulty of stabilizing aqueous colloidal dispersions of cosmetics.

Known cosmetic composition containing betulinic acid in the composition of extracts of various plants, designed to prevent and eliminate wrinkles, cellulite treatment, skin elasticity, improve skin color. [EP 0 717 983 B1 Cosmetic compositions containing betulinic acid]. The main effect of triterpenoid extracts, including betulin and betulinic acid, is manifested in the stimulation of collagen synthesis, which determines the anti-aging effect of the composition on the skin. The disadvantage of the proposed compositions is the instability of aqueous dispersions and the need to stabilize with a large amount of surfactants of synthetic origin.

Known stable composition made in the form of a powder-dusting composition: betulin (2.0-4.0 parts by weight), chlorophyll derivatives, talc, zinc oxide and starch (RU No. 2049462). This composition has limited use due to the dosage form and has only a drying effect.

Known composition, in which betulin and its derivatives are included in a stable composition with vegetable oils (sunflower, soybean, olive, palm) in the presence of alkyl-modified silicone [RU 2175326 C1]. The disadvantage of this composition is the presence of ethanol in the oil composition, which limits its use in cosmeceuticals, weak skin hydration.

The closest in composition to the proposed composition for the preparation of cosmetics is an active additive of betulin and / or its derivatives, containing vegetable oil and auxiliary substances, which are a mixture of hydrophilic and lipophilic surfactants that provide the best moisturizing properties [RU 2291684 C2]. We have chosen this composition as a prototype. The main disadvantage of this cosmeceutical composition is the relatively low permeability of betulin and / or its derivatives, as a result of which the activation of collagen synthesis, which is necessary for anti-aging cosmetics, is reduced, the required degree of hydration is not achieved.

The objective of the present invention is to create a highly effective composition for the preparation of cosmeceutical agents that cause high permeability of betulin and / or its derivatives, allowing to achieve a high degree of moisture, capable of activating collagen synthesis, and enhancing sunscreen properties.

The technical result is the activation of collagen synthesis, the achievement of a high degree of moisture, accompanied by sunscreen properties, high efficiency of the composition as an anti-aging agent with a slight whitening effect.

The technical result is achieved by a composition for the preparation of cosmetics containing betulin and / or its derivatives, vegetable oils and excipients, zinc oxide, with the following ratio of components:

betulin and / or its derivatives 0.1-20.0% zinc oxide particles 0.01-15.00% Excipients 0.01-5.00% vegetable oils up to 100.00%

Preferably as derivatives of betulin contains betulinic acid, betulonic acid, allobetulin, betulin diphosphate, lupeol, betulin diacetate.

Preferably, as vegetable oils, it contains vegetable fatty oils selected from: sunflower oil, olive oil, rice oil, almond oil, castor oil, cocoa butter, peach oil, apricot oil, amaranth oil, mustard oil, corn oil, sea buckthorn oil, red palm oil, camelina oil, pumpkin seed oil; and vegetable essential oils selected from: lavender oil, pine oil, geranium oil, thyme oil, eucalyptus oil, clove oil, tea tree oil, anise oil, and the ratio of vegetable fatty oils to vegetable essential oils is from 100: 1 to 5 :one.

Preferably it contains zinc oxide in nanoparticles with a size of 1-500 nm.

The composition can be used directly or for the preparation of cosmeceuticals in mild form in the form of an ointment, cream, paste, liniment, gel, aerosol.

The high efficiency of the proposed composition is due to the combined and synergistic action of the components of the composition - betulin and / or its derivatives, which contribute to the activation of collagen synthesis - the most important process in age-related skin changes, antioxidant, metabolic and immunomodulatory effects of zinc ions, high permeability of zinc oxide nanoparticles, high moisturizing ability vegetable essential oils, as well as the ability of zinc oxide to act as a UV filter.

The use of zinc oxide as a bleaching component and a component of light filters in an oleophilic medium is well known, however, all known compositions with zinc oxide do not contain it in the form of nanosized particles and, accordingly, do not exhibit the properties of an active substance delivery vector and do not provide high permeability of betulin and / or its derivatives.

At present, no proposed agent has been identified from the prior art.

The use of betulin and / or betulin derivatives in the composition - betulinic acid, betulonic acid, allobetulin, betulin diphosphate, lupeol, betulin diacetate at a concentration of less than 0.1% does not provide effective activation of collagen synthesis necessary for anti-aging cosmetics, and the introduction of these compounds in concentration more than 20% is not economically feasible.

The introduction into the composition of zinc oxide in a concentration of less than 0.01% does not provide the required permeability of betulin and / or its derivatives through the skin, and the introduction of zinc oxide in a concentration of more than 15% is not economically feasible.

To achieve the necessary moisture, the mass ratio of vegetable fatty oils and vegetable essential oils should not exceed 100: 1. When the mass ratio of vegetable fatty oils and vegetable essential oils is below 5: 1, side effects of essential oils caused by their high dose are possible.

Examples of specific production of the proposed composition for the preparation of cosmetics.

Example 1. Getting the proposed composition. Took (wt.%) 10.0 betulin, added 1.0 zinc oxide with a size of 10-50 nm, then added with stirring and sonication 0.01 auxiliary substances, 5.0 lavender oil and sunflower oil to 100.0.

Example 2. Obtaining the proposed composition. Took (wt%) 1.0 betulin, 1.0 betulin diacetate, added 10.0 zinc oxide with a size of 50-200 nm, then added with stirring and sonication 2.0 auxiliary substances, 3.0 pine oil and olive oil up to 100.0.

Example 3. Obtaining the proposed composition. Took (wt.%) 0.5 betulin, 2.0 betulonic acid, added 10.0 zinc oxide with a size of 50-100 nm, then added with stirring and sonication 0.7 auxiliary substances, 1.2 geranium oil and amaranth oil up to 100.0.

Example 4. Getting the proposed composition. Took (wt%) 19.0 betulin, 1.0 allobetulin, added 0.01 zinc oxide 1-50 nm in size, then added with stirring and sonication 0.05 auxiliary substances, 0.9 thyme oil and mustard oil to 100.0.

Example 5. Obtaining the proposed composition. Took (wt%) 3.0 betulin, 0.1 betulinic acid, added 8.0 zinc oxide with a size of 10-200 nm, then added, with stirring and sonication, 0.08 auxiliary substances, 14.8 eucalyptus oil and rice oil up to 100.0.

Example 6. Getting the proposed composition. Took (wt%) 12.0 betulin, 1.0 betulin diphosphate, added 0.5 zinc oxide with a size of 50-500 nm, then added with stirring and sonication 0.2 auxiliary substances, 8.63 thyme oil and olive oil up to 100.0.

Example 7. Getting the proposed composition. Took (wt.%) 7.0 betulin, 0.5 lupeol, added 7.0 zinc oxide with a size of 1-50 nm, then added with stirring and sonication 4.0 auxiliary substances, 3.3 geranium oil and rice oil to 100.0.

Example 8. The composition was obtained by analogy with example 7. The ratio of components: betulin diacetate - 10.0, zinc oxide nanoparticles with a size of 1-50 nm - 2.0, excipients - 0.3, thyme oil - 2.7, almond oil - up to 100.0.

Example 9. The composition was obtained by analogy with example 7. The ratio of the components: betulonic acid - 0.1, nanoparticles of zinc oxide with a size of 50-100 nm - 15.0, excipients - 5.0, eucalyptus oil - 1.7, castor oil - up to 100.0.

Example 10. The composition was obtained by analogy with example 7. The ratio of the components: allobetulin - 2.0, zinc oxide nanoparticles with a size of 10-200 nm - 10.0, auxiliary substances - 1.5, clove oil - 1.7, cocoa butter - up to 100.0.

Example 11. The composition was obtained by analogy with example 7. The ratio of components: betulinic acid - 0.1, zinc oxide nanoparticles with a size of 50-500 nm - 14.0, excipients - 0.3, tea tree oil - 1.3, peach oil - up to 100.0.

Example 12. The composition was obtained by analogy with example 7. The ratio of the components: betulin diphosphate - 4.0, zinc oxide nanoparticles with a size of 50-100 nm - 10.0, excipients - 1.0, anise oil - 0.84, apricot oil - up to 100.0.

Example 13. The composition was obtained by analogy with example 7. The ratio of components: lupeol - 6.0, nanoparticles of zinc oxide with a size of 10-200 nm - 7.0, auxiliary substances - 3.0, clove oil - 1.0, corn oil - up to 100.0.

Example 14. The composition was obtained by analogy with example 7. The ratio of the components: betulin diacetate - 8.0, zinc oxide nanoparticles with a size of 50-500 nm - 8.0, excipients - 1.0, eucalyptus oil - 1.0, sea buckthorn oil - up to 100.0.

Example 15. The composition was obtained by analogy with example 7. The ratio of the components: betulin - 9.0, betulonic acid - 0.3, zinc oxide nanoparticles with a size of 50-500 nm - 1.0, auxiliary substances - 2.0, thyme oil - 1.0, red palm oil - up to 100.0.

Example 16. The composition was obtained by analogy with example 7. The ratio of components: betulin - 11.0, betulin diacetate - 0.2, zinc oxide nanoparticles with a size of 50-100 nm - 3.0, auxiliary substances - 0.1, tea tree oil - 0.9, camelina oil - up to 100.0.

Example 17. The composition was obtained by analogy with example 7. The ratio of the components: betulin - 13.0, betulinic acid - 0.1, zinc oxide nanoparticles with a size of 10-200 nm - 5.0, auxiliary substances - 0.4, geranium oil - 0.8, pumpkin seed oil - up to 100.0.

Example 18. The composition was obtained by analogy with example 7. The ratio of the components: betulin - 16.0, allobetulin - 1.0, zinc oxide nanoparticles with a size of 1-50 nm - 1.0, auxiliary substances - 0.5, pine oil - 8 , 0, sunflower oil - up to 100.0.

Example 19. The composition was obtained by analogy with example 7. The ratio of components: betulin - 18.0, betulin diphosphate - 0.7, zinc oxide nanoparticles with a size of 50-500 nm - 1.0, auxiliary substances - 0.01, lavender oil - 5.4, olive oil - up to 100.0.

Example 20. The composition was obtained by analogy with example 7. The ratio of components: betulin diacetate - 10.0, zinc oxide with a particle size of 5-10 microns - 2.0, excipients - 0.3, thyme oil - 2.7, peach oil - up to 100.0.

Example 21. The composition is obtained by analogy with example 7. The ratio of the components: betulin - 13.0, betulinic acid - 0.1, zinc oxide with a particle size of 5-10 microns - 5.0, auxiliary substances - 0.4, tea tree oil - 0.8, sea buckthorn oil - up to 100.0.

Example 22. The composition is obtained by analogy with example 7. The ratio of components: betulin - 18.0, betulin diphosphate - 0.7, zinc oxide with a particle size of 5-10 microns - 1.0, auxiliary substances - 0.01, eucalyptus oil - 5.4, almond oil - up to 100.0.

The effectiveness of the proposed composition was studied experimentally on cell lines. Cell lines were worked on according to the method of Nakagawa, et. al., J. Inv. Derm., (1989), 93, pp. 792-798, and Jutley, J. K. et al., Matrix, (1993) 13, pp. 235-41.

The analysis procedure is similar to that described in EP 0 717 983 B1 "Cosmetic compositions containing betulinic acid".

The percentage of collagen synthesis was calculated using the formula described by Martens et al., Gut (1992), 33, pp. 1664-1670.

Was investigated stimulating activity in relation to the synthesis of collagen in the culture of fibroblasts, treated with the proposed compositions. Each experiment was compared to a prototype. The following parameters were evaluated:

1 - Total protein (DPM ± SE);

2 - Non-collagen protein (DPM ± SE);

3 - Percentage of collagen synthesis;

4 - Percentage improvement over control.

The results obtained for all evaluated parameters are presented in table 1, where the number of the example "P" is the prototype.

Table 1. Influence of the proposed compositions on collagen synthesis

Example No. Estimated parameter one 2 3 4 NS 21768 ± 1563 15734 ± 623 4.91 ± 0.30 - one 25923 ± 1524 20614 ± 364 7.31 ± 0.52 ≈148 2 26964 ± 1624 21517 ± 964 8.33 ± 0.42 ≈170 3 24851 ± 1520 20462 ± 496 7.31 ± 0.55 ≈149 4 24849 ± 1387 22175 ± 285 7.76 ± 0.58 ≈158 five 26972 ± 1320 20859 ± 590 8.64 ± 0.51 ≈176 6 25022 ± 1587 20331 ± 737 8.42 ± 0.58 ≈171 7 24863 ± 1425 20843 ± 625 8.99 ± 0.57 ≈183 eight 25981 ± 1870 22861 ± 698 7.43 ± 0.49 ≈151 nine 25729 ± 1251 21875 ± 604 7.92 ± 0.47 ≈161 10 27088 ± 1624 21429 ± 576 7.89 ± 0.42 ≈161 eleven 26408 ± 1503 21997 ± 534 6.92 ± 0.52 ≈141 12 25146 ± 1534 21824 ± 598 6.96 ± 0.49 ≈142 13 25418 ± 1653 22774 ± 673 8.93 ± 0.51 ≈182 fourteen 24600 ± 1592 22019 ± 634 8.54 ± 0.57 ≈174 fifteen 24342 ± 1548 21970 ± 597 8.32 ± 0.53 ≈169 sixteen 25335 ± 1634 22864 ± 512 7.52 ± 0.55 ≈153 17 23650 ± 1592 21839 ± 654 8.54 ± 0.51 ≈174 18 24418 ± 1581 21030 ± 621 8.72 ± 0.51 ≈178 nineteen 26349 ± 1571 21690 ± 589 7.21 ± 0.58 ≈147 twenty 25918 ± 1672 22176 ± 617 7.34 ± 0.61 ≈149 21 25839 ± 1522 21029 ± 633 7.73 ± 0.51 ≈157 22 26198 ± 1519 21387 ± 519 7.01 ± 0.55 ≈152

The permeability of the proposed compositions was investigated on a pig skin model in accordance with the method described in US 2019/0240134 A1, 2019 "A skincare cosmetic composition". The results are presented in table 2, where "P" - prototype, "B" - betulin, "DAB" - betulin diacetate, "DFB" - betulin diphosphate, "AlB" - allobetulin, "L" - lupeol, "Bink" - betulinic acid, "BonK" - betulonic acid.

Table 2. Absorption of betulin and / or its derivatives from the proposed compositions

Example No. The content of betulin and / or its derivatives (mg / g) Transdermal absorption of betulin and / or its derivatives (mg / g) NS 50-350 20.0 ± 0.8 / 102.1 ± 1.1 B one 100 B 67.0 ± 2.0 B 2 10B / 10 DAB 5.0 ± 1.0 B / 5.2 ± 0.8 DAB 3 5B / 20BonK 3.0 ± 0.8 B / 15.0 ± 2.0 BonK 4 190B / 10AB 83.0 ± 5.0 B / 8.0 ± 1.0 AB five 30B / 1Bink 17.0 ± 2.0 B / 0.4 ± 0.1 BinK 6 120B / 10DFB 83.0 ± 6.0 B / 7.0 ± 1.0 DFB 7 70B / 5L 38.0 ± 6.0 B / 4.0 ± 0.6 L eight 100.0DAB 62.0 ± 6.0 DAB nine 1BonK 0.7 ± 0.1 BonK 10 20ALB 8.0 ± 1.0 AlB eleven 1Bink 0.4 ± 0.1 BinK 12 40DFB 31.0 ± 3.0 DFB 13 60L 42.0 ± 5.0 L fourteen 80DAB 57.0 ± 7.0 DAB fifteen 90B / 3BonK 63.0 ± 4.0 B / 2.0 ± 0.3 Bonk sixteen 110B / 2DAB 73.0 ± 9.0 B / 1.0 ± 0.2 DAB 17 130B / 1Bink 84.0 ± 7.0 B / 0.7 ± 0.2 BinK 18 160B / 10AB 95.0 ± 7.0 B / 8.0 ± 1.0 AB nineteen 180B / 7DFB 120.0 ± 11.0 B / 5.0 ± 0.6 DFB twenty 100 DAB 61.0 ± 4.0 DAB 21 130B / 1 Bink 78.0 ± 7.0 B / 0.7 ± 0.1 BinK 22 180 B / 7 DFB 95.0 ± 5.0 B / 5.0 ± 1.0 DFB

The effectiveness of the composition was tested on volunteers (women from 22 to 65 years old). The compositions were applied to a 5 × 5 cm ² area of skin on the outside of the left forearm. All participants in the study noted an improvement in the condition of the skin, which was manifested in additional softening, moisturizing and whitening at the site of application of the composition. Overall satisfaction with the results of use was good, there were no negative reviews or allergic reactions. Table 3 shows the lowest efficacy score obtained in each of the groups of volunteers, where example number "P" is the prototype.

Table 3.

Example No. Group of volunteers Emollient action Moisturizing action Whitening effect NS 3 women 25.37 and 42 years old + + - one 3 women 38.45 and 48 years old + ++ + 2 3 women 27,32 and 45 years old ++ +++ + 3 3 women 31.43 and 52 years old +++ + + 4 3 women 45.47 and 53 years old ++ +++ + five 3 women 42.46 and 57 years old ++ + + 6 3 women 32.37 and 41 years old +++ + + 7 3 women 45.47 and 51 years old + ++ + eight 3 women 27.48 and 52 years old +++ ++ ++ nine 3 women 33.36 and 39 years old ++ +++ ++ 10 3 women 28.43 and 50 years old ++ ++ + eleven 3 women 27.49 and 62 years old +++ ++ + 12 3 women 22.43 and 65 years old +++ ++ ++ 13 3 women 34.41 and 52 years old +++ ++ + fourteen 3 women 34.45 and 53 years old ++ ++ + fifteen 3 women 31, 34 and 46 years old +++ +++ ++ sixteen 3 women 31, 33 and 36 years old ++ ++ + 17 3 women 41, 43 and 49 years old ++ ++ ++ 18 3 women 21, 25 and 33 years old ++ +++ + nineteen 3 women 51, 57 and 60 years old ++ +++ + twenty 3 women 26.31 and 42 years old +++ +++ + 21 3 women 29, 31 and 34 years old ++ ++ + 22 3 women 35, 41 and 45 years old ++ ++ +

"-" - no effect compared to the baseline

"+" - a visible improvement in the indicator compared to the initial

"++" - a significant improvement in the indicator compared to the initial

"+++" - complete elimination of irritation-induced disturbances

Claims (2)

A composition with moisturizing, sunscreening properties, activating collagen synthesis, for the preparation of cosmetics for the skin, containing betulin and / or its derivatives selected from betulinic acid, betulonic acid, allobetulin, betulin diphosphate, lupeol, betulin diacetate, zinc oxide in the form of nanoparticles 1-500 nm in size, vegetable oils and auxiliary substances, characterized in that a mixture of vegetable fatty oils and vegetable essential oils is used in a mass ratio of 100: 1 to 5: 1, while vegetable fatty oils selected from: sunflower oil, olive butter, rice oil, almond oil, castor oil, cocoa butter, peach oil, apricot oil, amaranth oil, mustard oil, corn oil, sea buckthorn oil, red palm oil, camelina oil, pumpkin seed oil; and vegetable essential oils selected from: lavender oil, pine oil, geranium oil, thyme oil, eucalyptus oil, clove oil, tea tree oil, anise oil, and auxiliary substances, in the following ratio of components, wt. %: betulin and / or its derivatives 0.10-20.00 zinc oxide particles 0.01-15.00 Excipients 0.01-5.00 a mixture of vegetable fatty oils and vegetable essential oils up to 100.00