RU2809099C1 - Cream that absorbs ultraviolet radiation, based on viburnum red and silver nanoparticles and method of its preparation - Google Patents

Abstract

FIELD: pharmaceutical; cosmetic industry.

SUBSTANCE: group of inventions relates to a cream that absorbs ultraviolet radiation and a method of its production. A method of producing a cream absorbing ultraviolet radiation is as follows: the fruits of red viburnum are crushed, the seeds are removed, the resulting mass is squeezed, an equal amount of aqueous-ethanol solution at a ratio of alcohol to water 3:7 is added to the resulting juice of 20 ml, it is extracted for 48 hours at room temperature, the resulting solution is passed through gauze three times and then through paper filters until a clear, bright red liquid is obtained, the resulting clear solution is filtered through a filter with a fraction size of 200 nm, an aqueous solution of silver nanoparticles with a volume of 0 is added to the resulting solution with a volume of 2 ml, an aqueous solution of silver nanoparticles in a volume of 0.1 ml with concentration C_Ag=5⋅10^-8 M is added, then the aqueous-alcoholic extract of viburnum with silver nanoparticles is added to a mixture consisting of 0.5 ml of glycerol monostearate and 10 ml of medium-chain glycerides, stirred until homogeneous on a magnetic stirrer for 15 minutes at 800 rpm and a temperature of 50°C, the resulting emulsion is treated in an ultrasonic bath with a frequency of 37 kHz for 10 minutes. Cream that absorbs ultraviolet radiation, obtained as described above.

EFFECT: cream obtained by the method described above intensively absorbs light in the region of 350–500 nm, increases the degree of absorption as a result of plasma resonance of silver nanoparticles.

2 cl, 3 dwg

Description

The invention relates to the field of physicochemical and/or cosmetology industry, and is an ultraviolet-absorbing cream based on the fruit extract of red viburnum (Viburnum Opulus L.) and silver nanoparticles (NPs). The biologically active cream has the property of absorption in the ultraviolet region of the spectral range. Plasmons of silver nanoparticles increase the optical density and enhance the absorption property of the cream when interacting with UV radiation. The invention can be used in biophysics, medicine and pharmaceuticals as a sunscreen and antioxidant drug.

There are known works that are prerequisites for the claimed invention. The following examples form part of the background of the claimed invention and/or disclose techniques that can be applied to certain aspects of the claimed invention.

In particular, in the work (Pietrzyk, N.; Zaklos-Szyda, M.; Koziolkiewicz, M.; Pods,edek, A. Viburnum opulus L. Fruit Phenolic Compounds Protect against FFA-Induced Steatosis of HepG2 Cells via AMPK Pathway. J . Funct. Foods 2021, 80, 104437.) polyphenolic compounds of red viburnum were synthesized. Fresh juice was obtained by centrifugation (5000 rpm for 10 min) of homogenized fresh berries. The purification process was carried out by solid-phase extraction using methanol and water. Phenolic compounds loaded onto the columns were eluted with methanol and after removing the organic solvent under vacuum, the dry residue was diluted in water and freeze-dried to obtain purified juice. The solid residue obtained after centrifugation of the juice was used to prepare two preparations: based on methanol-acetone extract and acetone extract. Extracts of viburnum (V. opulus) have been found to increase polarization of the mitochondrial membrane, which may be due to their antioxidant properties. Thus, phenolic compounds in viburnum provide a dietary mechanism for regulating liver lipotoxicity in obese individuals. In addition, phenolic compounds in viburnum may suppress insulin resistance resulting from hyperlipidemia by enhancing signaling through the insulin receptor pathway.

The presented studies have proven that viburnum juice, as well as residues from viburnum juice, may be a rich source of bioactive compounds that are widely used in the prevention and treatment of hepatic steatosis, and indicate that viburnum fruit may be a potential functional food ingredient. The biological activity of viburnum fruits is also well described in (Chen, J.; Zhao, Z.; Zhang, X.; Shao, J.; Zhao, C. Recent Advance on Chemistry and Bioactivities of Secondary Metabolites from Viburnum Plants: An Update Chem. Biodivers. 2021, 18, e2100404).

In (Bozali, K.; Guler, EM; Gulgec, AS; Kocyigit, A. Cytotoxic, Genotoxic and Apoptotic Effects of Viburnum opulus L. on Colon Cancer Cells: An in Vitro Study. Turkish J. Biochem. 2020, 45, 803-810.) the content of flavonoids in the extract was determined spectrophotometrically, quercetin was used as a standard. The flavonoid content based on the ABTS method was 1-8 mg/ml. To determine the total polyphenolic mass of viburnum extract, gallic acid was used as a standard. The Folin-Ciocalteu reagent was added to 40 μl of the extract, and the mixture was incubated at room temperature for 8 min. After incubation, 60 μl of 7.5% Na ₂ CO ₃ was added to the mixture. The solutions were incubated at 25°C for 2 hours. The test results were compared with gallic acid. The absorbance of viburnum extract was measured at 746 nm. The disadvantage of this method is the consideration of absorbance at a wavelength of 746 nm, since the main absorption maxima for viburnum extract are located in the region of ≈300 and ≈420 nm, depending on the extractant.

The review (Kajszczak, D.; Zaklos-Szyda, M.; Pods edek, A. Viburnum opulus L.-A Review of Phytochemistry and Biological Effects. Nutrients 2020, 12, 3398.) presents the rich and diverse chemical composition of viburnum extract. Due to its high content of phenolic compounds, as well as other components with antioxidant potential, viburnum has the ability to neutralize or scavenge free radicals through chemical interaction with active molecules. Viburnum fruit juice as well as isolated phenolic compounds (50-75 μg/ml) showed protective activity against oxidative stress generated by t-BOOH in human hepatoma cells HepG2 secreting insulin β-TC3 and MIN-6, and also partially restored their metabolic activity [Zaklos-Szyda, M.; Majewska, I.; Redzynia, M.; Koziolkiewicz, M. Antidiabetic effect of polyphenolic extracts from selected edible plants as α-amylase, α-glucosidase and PTP1B inhibitors, and β pancreatic cell cytoprotective agents-A comparative study, 22-Zaklos-Szyda, M.; Kowalska-Baron, A.; Pietrzyk, N.; Drzazga, A. Evaluation of Viburnum opulus L. Fruit phenolics cytoprotective potential on insulinoma MIN6 cells relevant for diabetes mellitus and obesity. Antioxidants 2020, 9, 433]. Recent in vitro studies showed that juice isolated from viburnum fruit acted as a protective agent against DNA damage induced in human Caco-2 adenocarcinoma cells by methyl-nitronitrosoguanidine (MNNG) or hydrogen peroxide [Zaklos-Szyda, M.; Pawlik, N.; Polka, D.; Nowak, A.; Koziolkiewicz, M.; Pods,edek, A. Viburnum opulus fruit phenolic compounds as cytoprotective agents able to decrease free fatty acids and glucose uptake by Caco-2 cells. Antioxidants 2019, 8, 262]. Fresh juice and phenolic compounds isolated from it (100 and 25 μg/ml, respectively) also revealed a positive effect on DNA repair after damage caused by MNNG in Saos-2 cells [25-Zaklos-Szyda, M.; Nowak, A.; Pietrzyk, N.; Pods.edek, A. Viburnum opulus L. juice phenolic compounds influence osteogenic differentiation in human osteosarcoma Saos-2 cells. Int. J. Mol. Sci. 2020, 21.4909].

The invention “Apsorin” is known (patent RU 2082426), which includes aqueous-alcoholic extracts of wormwood, viburnum, radiola and licorice, which describes a method for treating psoriasis by applying the extracts to the affected areas of the skin. The drug is obtained from plant raw materials having a component ratio, wt. %: lemon wormwood leaf 15-40; viburnum root 30-35; Rhodiola rosea root 30-50. The method involves extracting lemon wormwood leaves with ethyl alcohol in a water bath with reflux at a ratio of initial plant material: extractant of 1:3 and subsequent infusion in the resulting extract of viburnum root and Rhodiola rosea root. The subject of the invention is also a method for treating psoriasis, including applying the above-mentioned drug “Apsorin” to the affected areas of the skin with simultaneous oral administration of an infusion of licorice root. The application of the drug "Apsorin" alternates with the application of an emollient cream, and an infusion of licorice root is administered in an amount of up to 250 ml per day.

Another known invention is “Antimicrobial activity of biologically stabilized silver nanoparticles” (patent EA 013401 B1), containing a selection principle similar to that used in the claimed method and a method for constructing a device. The invention relates to an antimicrobial composition containing biologically stabilized silver nanoparticles, stabilized using “green” biological pathway, with an average size of 1-100 nm in a carrier (gel, cream, etc.), the concentration of which ranges from 1 to 6 ppm.

The average particle size is 1-100 nm. The invention proves the antimicrobial activity of the composition at a very low effective concentration (due to the extremely high surface area) and is not cytotoxic at these concentrations. The composition contains: biologically stabilized silver nanoparticles with a size ranging from 1 to 100 nm and a carrier (gel, cream, ointment, etc.), in which the concentration of these biologically stabilized silver nanoparticles is in the range from 1 to 6 ppm.

The main disadvantage of this invention is the uneven size distribution of nanoparticles. Due to the large size dispersion (1 to 100 nm), coagulation processes of nanoparticles (sticking together) in the carrier matrix are possible, which can subsequently lead to partial destruction of the composition and separation of the water-oil fractions.

The prototype of this invention is the invention “Therapeutic and cosmetic product for protecting the skin from sunburn” (patent RU 2475230 C1 (Two Lines LLC) 02/20/2013).

The invention relates to the field of cosmetology and is a therapeutic and cosmetic product for protecting the skin from sunburn, characterized in that it is made in the form of an aerosol cream containing D-panthenol, allantoin, colloidal nanosilver, bisabolol, supercritical extract of common spruce needles, supercritical extract calendula officinalis, supercritical extract of sea buckthorn, supercritical extract of rosemary, supercritical extract of clary sage, supercritical extract of wheat germ, supercritical extract of chamomile, supercritical extract of tripartite, supercritical extract of St. John's wort, as well as anhydrous lanolin, triethanolamine, ethyl alcohol, synthetic alcohols fatty primary fractions C ₁₆ -C ₂₁ , stearic acid, distilled glycerin, sunflower oil, liquefied hydrocarbon gas or a mixture of freons 22 and 142, purified water, and the components in the product are in a certain ratio by weight. %.

The disadvantage of this invention lies in the presence of a large amount of plant raw materials used, which is included in the formulation in the form of expensive supercritical extracts.

The aerosol cream also contains purified hydrocarbon liquefied gas or a mixture of freons 22 and 142, the use of which is not environmentally friendly and unsafe for human health, especially with diseases of the respiratory system.

The objective of the claimed invention is to develop a method for producing a bioactive cream capable of intensely absorbing light in the region of 350-500 nm and increasing the degree of absorption as a result of plasmon resonance of silver nanoparticles.

The problem is solved by the fact that the bioactive cream is a creamy base with an active substance (viburnum fruit extract with silver NPs), which has an intense absorption spectrum in the ultraviolet region due to the presence of silver nanoparticles in the aqueous-alcoholic extract of viburnum fruits.

The claimed method allows one to obtain a wide absorption spectrum of UV blue light with intense optical density in the ultraviolet.

The claimed method is based on the effect of double absorption by active compounds of viburnum red fruit extract and silver nanoparticles, evenly distributed in a creamy matrix (glycerol monostearate in fatty acid triglycerides) at close range with silver NPs, which allows increasing the absorption capacity of the substance.

The preparation of aqueous-alcoholic extract of viburnum Viburnum opulus L. fruits on a cream base was carried out as follows.

First, fresh viburnum fruits, pre-peeled, weighing 213 g, were crushed in a mortar and the seeds were removed, then the resulting mass was squeezed out. An equal amount of aqueous-ethanol solution in a ratio of alcohol to water of 3:7 was added to the resulting juice (20 ml), and the extraction was carried out for 48 hours at room temperature. The resulting solution was passed through cheesecloth three times and then repeatedly passed through paper filters until a clear, bright red liquid was obtained. The resulting clear solution was filtered through a filter with a fraction size of 200 nm. After settling for 24 hours, no sediment formed.

To the resulting solution with a volume of 2 ml, a solution of silver nanoparticles with a volume of 0.1 ml was added, prepared by the following method: 22.5 mg of AgNO ₃ was dissolved in 250 ml of distilled water. The solution was brought to a boil with vigorous stirring, after which 4.5 ml of an aqueous solution of sodium citrate with a concentration of 1% was quickly added dropwise. Immediately after mixing the reagents, the solution took on a yellow-green color. Since the silver particles were obtained with a certain excess of the reducing agent, we can assume that almost all of the original silver was reduced to the metallic state. The concentration of the resulting solution was C _Ag =5⋅10 ^-8 M. The average hydrodynamic radius of the resulting nanoparticles was studied by photon correlation spectroscopy (PhotoCor-Complex, Belarus) and was 30 nm.

Next, the aqueous-alcoholic extract of viburnum with silver nanoparticles was added to a mixture consisting of glycerol monostearate (0.5 ml) and medium-chain glycerides (10 ml). Stir thoroughly until homogeneous on a magnetic stirrer (15 minutes, V=800 rpm, T=50°C). The resulting emulsion was treated in an ultrasonic bath (with a frequency of 37 kHz) for 10 minutes. The resulting cream had a uniform soft texture, pink in color, without any other accumulations in the form of large complexes (lumps).

The prepared solutions of extracts with silver nanoparticles and a cream based on the extract with silver nanoparticles were studied in the ultraviolet and visible region using the spectrophotometric method on a spectrophotometer from Shimadzu (Japan). The absorption spectra of a solution of silver nanoparticles are presented in Fig. 1., where: 1 - solution of silver nanoparticles with concentration C=5⋅10 ^-8 M; 2 - solution of viburnum fruit extract; 3 - solution of viburnum fruit extract with silver nanoparticles with concentration C=5⋅10 ^-8 M.

The absorption spectra of a solution of viburnum fruit extract and silver NPs overlap in the region of 420 nm. When silver NPs are added to the extract solution, the optical density increases as a result of double photoexcitation of absorbing substances, followed by the total spectral addition of the integral optical density. The optical absorption density of a cream based on viburnum fruits with silver NPs also increases as a result of the presence of plasmonic NPs that absorb in the same spectral region as the cream based on viburnum. In FIG. 2. The absorption spectra of creams based on red viburnum fruits are presented, where: 1 - without silver nanoparticles; 2 - with silver nanoparticles with a concentration of C = 5⋅10 ^-8 M. The absorption maxima of creams shift to the UV region at a wavelength of 380 nm. The optical density of the cream based on viburnum fruits with silver NPs is higher than that of the cream without NPs. Photographs of the resulting cream masses are presented in Fig. 3, where: 1) photograph of a sample of the resulting cream based on the extract of red viburnum fruits without silver nanoparticles; 2) photograph of a sample of the resulting cream based on the extract of red viburnum fruits with silver nanoparticles.

Claims (2)

1. A method for producing a cream that absorbs ultraviolet radiation, characterized in that the fruits of red viburnum are crushed, the seeds are removed, the resulting mass is squeezed out, an equal amount of aqueous-ethanol solution is added to the resulting juice of 20 ml in a ratio of alcohol to water 3:7, extracted into for 48 hours at room temperature, the resulting solution is passed through cheesecloth three times and then through paper filters until a clear, bright red liquid is obtained, the resulting clear solution is filtered through a filter with a fraction size of 200 nm, an aqueous solution of silver nanoparticles is added to the resulting solution with a volume of 2 ml volume of 0.1 ml with a concentration of C _Ag = 5⋅10 ^-8 M, then the aqueous-alcoholic extract of viburnum with silver nanoparticles is added to a mixture consisting of 0.5 ml of glycerol monostearate and 10 ml of medium chain glycerides, stirred until homogeneous on a magnetic stirrer for 15 minutes at 800 rpm and a temperature of 50°C, the resulting emulsion is treated in an ultrasonic bath with a frequency of 37 kHz for 10 minutes. 2. Cream that absorbs ultraviolet radiation, obtained by the method according to claim 1.