Composition

Abstract

The hyaluronic acid has a molecular weight of 10 to 1000 KDa absorbed into activated smectite clay, and the hyaluronic acid-clay combination has a molecular weight of 3 to 10 M. 2 / g and a particle size (VSSA) of 250-500 nm. Application of such a treatment to the skin allows for significantly deeper penetration into the skin than either hyaluronic acid alone or a simple hyaluronic acid-clay blend.

Description

[Technical field]

[0001] The present disclosure relates to methods of skin treatment and compositions for providing such treatment. [Background technology]

[0002] Hyaluronic acid is a naturally occurring glycosaminoglycan found throughout the connective tissues of the body. It is the main component that gives skin its structure and is responsible for providing it with a plump and moisturized appearance. As a result, a number of hyaluronic acid-based skin treatment preparations have emerged in recent years. Summary of the Invention

[0003] For best results, it is desired that hyaluronic acid penetrates deep into the skin. With conventional skin creams, this has not always been possible. Now, surprisingly, it has been found that a particular delivery vehicle can provide significantly deeper skin penetration, with a simultaneous improvement in skin condition. Thus, a hyaluronic acid-clay combination comprising hyaluronic acid with a molecular weight of 10-1000 KDa absorbed into activated smectite clay, with a hyaluronic acid-clay combination of 3-10 M 2 A skin treatment preparation is provided having a non-porous specific surface area of ​​100 nm / g and a particle size (VSSA) of 250 to 500 nm.

[0004] Additionally, methods are provided for providing hyaluronic acid to the skin, the hyaluronic acid comprising a portion of a hyaluronic acid-clay combination as described herein.

[0005] Additionally, there is provided an activated smectite clay having hyaluronic acid formulated therein, the hyaluronic acid-clay formulation being between 3 and 10M 2 / g and a particle size (VSSA) of 250 to 500 nm. Volume Specific Surface-Area (VSSA) is an integral measurement that provides an indirect representation of particle size.

[0006] Smectite clays are a group of 2:1 layered plate-like phyllosilicate materials with a layer charge of about -0.2 to -0.6 per formula unit. They have large specific surface areas and exhibit a high degree of swelling in water. A specific example of a smectite clay is montmorillonite, more specifically bentonite.

[0007] Combinations of hyaluronic acid ("HA") and clay are known and commercially available as part of skin care treatments. However, it has been surprisingly found that the combination as defined herein above can penetrate much deeper into the skin than a simple mixture of HA and clay can.

[0008] The parameters of the HA-clay blends of the present disclosure cannot be achieved by simple mixing. The preparation of the HA-clay blends of the present disclosure is carried out by applying extremely high shear forces in a rotor / stator mixer, similar to those that occur in an extruder reactor. Any such mixer may be used, such as ball mills, ribbon blenders, paddle blenders, screw blenders, and double cone blenders.

[0009] Prior to formulation, the smectite clay is activated. This may be any type of activation known in the art, a typical example being acid activation, as described, for example, by Maged et al. in Environmental Science and Pollution Research, 27, pp.32980-32997 (2020). After drying and sieving, the activated smectite clay is subjected to high shear forces. The shear time will depend on the specific material and shear method used, but the skilled person can easily ascertain a suitable period in each case by simple experimentation. A typical, non-limiting shear time would be from 15 minutes to 2 hours, in particular from 30 minutes to 1 hour.

[0010] Without limiting this disclosure in any way, it is believed that pressure and shear force have the ability to increase the interaction between clay and HA. Moreover, it is believed that under such a combination of pressure (>1 bar) and shear force, the layered structure of the clay opens up, making the hydroxyl groups on the edges of the clay platelets more accessible. Again, without limiting this disclosure in any way, it is believed that the mechanism of interaction is through hydrogen bonding between hydrophilic moieties (such as carboxylic acid or hydroxyl groups) in HA and hydroxyl groups on the clay.

[0011] Again, without limiting the present disclosure in any way, it is believed that the interaction between HA and clay gives HA a strong anionic character, with a lower electric potential measured by zeta potential, which is significantly different from the characteristics of HA alone.This electric behavior is believed to make the skin affinity with the biological epidermis layer better, leading to HA's skin penetration, whereas HA alone cannot penetrate at all.It is known that there is a natural pH gradient in the skin, which leads to the presence of more positive charges on the surface.As a result, hyaluronic acid applied alone tends to remain at or near the surface of the skin.

[0012] In a specific embodiment, the specific surface area is 4 to 9, more specifically 5 to 8 M 2 In another specific embodiment, the particle size (VSSA) is from 280 to 450, more specifically from 300 to 430 nm. These numbers are lower (for specific surface area) and higher (for particle size) due to the method of manufacture of the HA-clay blends of the present disclosure.

[0013] The active smectite clay may be used unmodified, but in a specific embodiment, it may be modified with fatty substances to enhance absorption into the skin.Representative substances include fats and oils of animal, vegetable or mineral origin, and hydrocarbon-based waxes, silicone oils or mixtures thereof.Specific examples of hydrocarbon-based modifying agents include fats and oils of vegetable and animal origin, more particularly triglycerides; synthetic ethers; linear or branched hydrocarbons of mineral or synthetic origin, such as petrolatum; synthetic esters such as isopropyl myristate and fatty alcohol benzoate; heptanoate, octanoate, decanoate or ricinoleate of alcohol or polyhydric alcohol; hydroxylated esters such as isostearyl lactate, esters of polyols; fatty alcohols such as octyl dodecanol; higher fatty acids such as linoleic acid; silicone oils of polymethylsiloxane type, and mixtures thereof.

[0014] Examples of vegetable waxes include carnauba, candelilla, jojoba wax, or any other vegetable compound consisting of an ester of ethylene glycol with two fatty acids or a monoester of a fatty acid with a long-chain alcohol; animal waxes such as beeswax. Other fatty substances and lipophilic additives include essential oils; natural aromatic compounds and lipophilic synthetics; natural or synthetic fat-soluble vitamins, such as tocopherol or alpha tocopheryl acetate.

[0015] The proportion of fatty substances in the clay typically varies from 0.05 to 14.5% by weight. The hyaluronic acid of the present disclosure has a molecular weight of 10-1000 KDa, specifically 20-1500 KDa, more specifically 50-1400 KDa, more specifically 100-1100 KDa, and even more specifically 300-1000 KDa. It may be added as an acid or as an alkali metal salt (typically sodium) with a suitable acid, such as citric acid, to generate the acid.

[0016] Modified clay may be processed into skin treatment preparations by any known means.The preparation may contain all the usual ingredients of such preparations in the proportions recognized in the art.Non-limiting examples include vitamins, antioxidants, thickeners, trace elements, emollients, sequestering agents, fragrances, basifying or acidifying agents, preservatives, UV filters, hydrophilic or lipophilic active ingredients, and mixtures thereof.

[0017] Hyaluronic acid is present in such preparations in a weight percentage of 5 to 15%, particularly 8 to 12%, more particularly 9 to 11%.

[0018] The surprising effect of this special combination of smectite clay and hyaluronic acid is that it penetrates particularly deep into skin.Without limiting this disclosure in any way, it is believed that clay modifies the zeta potential of hyaluronic acid, making the combination more negatively charged.It is known that there is a natural pH gradient in skin, which leads to the presence of more positive charges on the surface.As a result, hyaluronic acid tends to remain at or near the surface of skin.However, the negative charge imparted by clay allows it to penetrate deeper into skin, resulting in beneficial effects.

[0019] An additional unexpected and surprising benefit is the enhanced sense of well-being among people to whom the preparations according to the present disclosure have been applied to the skin, a benefit that has been scientifically verified by testing procedures further described in the examples.

[0020] The present disclosure is further described with reference to the following non-limiting figures and examples. [Brief description of the drawings]

[0021] [Figure 1]FIG. 1 is a graphical representation of the depth of penetration of hyaluronic acid into the skin when applied alone and in a simple blend with clay as commercially available. [Diagram 2] FIG. 2 is a repeat of FIG. 1, but with the simple clay-hyaluronic acid formulation replaced by the hyaluronic acid-clay formulation described in this disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Example 1 Testing on skin creams (a) Preparation of hyaluronic acid-clay blends A hyaluronic acid-clay blend was prepared by taking commercially available bentonite clay, activating it by the method of Maged et al., Environmental Science and Pollution Research, 27, pp. 32980-32997 (2020), drying it, sieving it through a 100 μm filter, adding sodium hyaluronate to it, and then shearing the mixture in a high shear ribbon blender for 1 hour.

[0023] (b) Preparation of test skin cream Two test skin creams were prepared by combining the following ingredients: [Table A]

[0024] (c) Cream test The test subjects were 20 women in the age range of 35-55 years, all of whom had dry skin, shallow wrinkles and crow's feet. They were divided into two groups, named Group A and Group B. Group A applied Cream 1 and Group B applied Cream 2.

[0025] All subjects applied the cream to their face twice a day, in the morning and in the evening. The skin was examined immediately before the first application, and then at 1 hour, 6 hours, 7 days, and 28 days. The examination was carried out using a Visia™ CR2.3 visual scanner (Canfield Scientific), which measured the area of ​​crow's feet wrinkles. The results are shown in the following table:

[0026] [Table B]

[0027] Thus, the improvement provided by Cream 1 is 17.4% after 1 hour, 16.5% after 6 hours and 22.7% after 28 days.

[0028] Example 2 Demonstration of skin penetration of hyaluronic acid when used in formulations prepared according to the present disclosure.

[0029] The following materials were tested: - Untreated clay ("untreated") - Hyaluronic Acid (HA) - HA + clay ("simple mixture") - an HA-clay formulation according to this description ("HA Clay")

[0030] HA was used at 1% by weight in distilled water, and the simple mixture and HA clay were used at 10% by weight in distilled water, both containing 1% by weight hyaluronic acid.

[0031] Human skin explants from a 47-year-old donor were prepared and kept in survival medium (MIL215001, Biopredic) at 37°C and 5% CO2 for 24 hours. The next day, HA clay and HA were applied topically and incubated at 37°C and 5% CO2 for 8 hours, after which skin penetration analysis was performed. Untreated samples were used as controls. After the end of incubation, the skin surface was washed to remove any excess product. The skin explants were then frozen at -80°C and sectioned longitudinally at a thickness of 20 μm using a cryotome. For each explant, three tissue sections were selected and placed on CaF2 supports for Raman imaging analysis for a total of nine Raman images per condition. Three other adjacent sections at a thickness of 7 μm were prepared for hematoxylin-eosin staining.

[0032] The Raman images had a size of Y: 10 μm / X: 100 μm with steps of 5 μm in X and 5 μm in Y. Each Raman image contained 3 Y spectra and 21 X spectra (63 spectra per image). Laser wavelength: 600nm Objective: 100x, long focal length, numerical aperture 0.75 ·Acquisition time: 25 seconds Accumulation: 1X Spectral range: 400~4000cm -1 Grating: 950T Confocal hole: 300μm Slit width: 150μm (spectral resolution 6.5cm -1 ) Step in X: 5μm, Step in Y: 5μm

[0033] To ensure the reproducibility of measurements, the Raman spectrometer was calibrated at 520.7 cm -1 The Raman peak was calibrated with silicon, which produces a Raman peak at 1000 .mu.m. Continuous control of the laser power at the sample level was achieved.

[0034] Pre-processing of the Raman images was performed by removing anomalous spectra (fluorescence, burning, saturation), correcting the baseline, applying spectral smoothing and despiking as well as spectral normalization.

[0035] Processing of the correction data maps was carried out using software based on the least squares fitting method run by Matlab software. This method involves mathematical modeling of reference spectra throughout the spectral image to determine the contribution and distribution of these spectra within the image. In this study, the average spectra of hyaluronic acid and clay were used as reference spectra.

[0036] From Figures 1 and 2, it can be observed that the penetration of the HA clay into the skin is considerably deeper than HA alone or the simple mixture. The clay alone has little penetration into the skin, which conclusively indicates that the HA clay combination produced according to the present disclosure results in much deeper skin penetration.

[0037] Example 3 Demonstration of an enhanced feeling of well-being experienced by a recipient of a composition as described herein above.

[0038] (a) Preparation of Skin Cream Two skin creams were prepared, one containing the hyaluronic acid / clay blend prepared according to Example 1, and the other not containing the blend and used as a placebo. The formulations are shown below, cream 3 is the cream containing the hyaluronic acid / clay blend and cream 4 is the placebo.

[0039] [Table C-1] [Table C-2]

[0040] 1 Carbopol™ ETD 2050, manufactured by Lubrizol 2 Symdiol™ 68, manufactured by Symrise 3 Dubcare™ GPE 810, manufactured by Stearinerie Dubois 4 Miglyol(TM) 812N, manufactured by IOI Oleo GmbH Viscosity at 5 mPa.s (Brookfield DVIII Ultra, Spindle F, Speed ​​12@20℃)

[0041] (b) Skin cream testing The study was carried out on 59 subjects, 42 women and 17 men, with a mean age of 38 years, all from the general population. The study was a double-blind study, and the investigators also did not know whether Cream 3 or Cream 4 was being presented to the study subjects.

[0042] The test was performed by the subjects by applying the product to the hands on two consecutive days. Before and after the test, the test subjects were asked to complete the questionnaire shown on the following page. The questionnaire was presented on a computer screen, and each question was accompanied by a slider that could be moved to indicate a position between "not at all" (value=0) and "extremely sensitive" (value=10). The screen display is shown below:

[0043] [Table D-1] [Table D-2]

[0044] For this study, a well-being metric was used to measure the effect of the test cream on the well-being of the test subjects. The well-being metric, described in detail in International Publication WO 2020 / 165463, to which reference may be made, was defined by applying experimental psychology and unsupervised clustering of linguistic attributes of well-being to identify the most appropriate dimensions for assessing well-being. The well-being attributes take into account various aspects of well-being, such as affective, eudaimonic, social, and material aspects. These aspects may include both affective (emotional) and cognitive (rational) components.

[0045] Weights for the happiness attributes were determined as follows: a) administering to one or more human subjects a happiness score, wb, for each of the WB-18 attributes; i 2. Having the subjects assess their sense of well-being in the absence of the test cream by providing b) Determine the impact of each well-being attribute on overall well-being to produce a well-being factor F j applying a factor analysis, in particular a principal components analysis, to the well-being scores obtained in step a) in order to yield i) Here, the happiness factor F j Each of the variables is expressed as a percentage of the sum of the variances of all happiness factors, v i having; ii) Here, the happiness factor F j Each of these is a finite number n j This includes the happiness attribute of n j Loadings expressed as a percentage of the sum of the individual loadings i and iii) where none of the well-being attributes appears in more than one well-being factor; and c) Calculate the Happiness Score in the absence of the test fragrance according to the following formula:

number

[0046] Principal component analysis revealed the following: - The well-being attributes “not anxious”, “not sad”, “not restless”, “not frustrated”, and “not stressed” are associated with the first well-being factor F1 with variance v1; - The well-being attributes “happy”, “optimistic”, “excited”, “satisfied”, “motivated” and “energetic” are associated with a second well-being factor F2 with variance v2; - The well-being attributes "interested" and "not bored" are associated with a third well-being factor F3 with variance v3; - The well-being attributes "not fatigued" and "mentally alert" are associated with the fourth well-being factor F4 with variance v4; - The well-being attributes "calm", "relaxed" and "patient" are associated with the fifth well-being factor F5 with variance v5; - The variance v1 is 48% of the sum of the variance of all happiness factors; - The variance v2 is 24% of the sum of the variance of all happiness factors; - variance v3 is 12% of the sum of the variance of all happiness factors; - variance v4 is 9% of the sum of the variances of all happiness factors; and - Variance v5 is 7% of the sum of the variance of all happiness factors.

[0047] Furthermore, as listed in Table 1, each attribute was found to have a loading within each factor (F1, F2, F3, F4, F5). [Table 1]

[0048] Using this methodology, the numerical results from the tests were summed to provide an average value for each attribute for each cream, and then these individual attribute scores were summed to provide an overall well-being score for each cream.

[0049] The results for overall well-being are shown in Table 2. [Table 2]

[0050] The results for positive well-being attributes (excited, happy, energetic, motivated, optimistic, satisfied) before and after the application are shown in Table 3. [Table 3] Cream 3 has a higher mean score for all individual positive attributes both before and after application.

[0051] The overall scores from Table 3 are summarized in Table 4. [Table 4] This indicates that Cream 3 provides a significantly higher change in perception of well-being than Cream 4.

[0052] The overall result is that 46 of 59 test subjects experienced enhanced well-being sensations when tested with cream 3, i.e. 78% of the subjects experienced enhanced well-being sensations as a result of exposure to the cream containing hyaluronic acid as described herein above.The overall scores of test subjects before and after cream 3 are shown in Table 5.

[0053] [Table 5]

Claims

1. The hyaluronic acid-clay blend comprises hyaluronic acid having a molecular weight of 10 to 1000 KDa absorbed into activated smectite clay, the hyaluronic acid-clay blend having a molecular weight of 3 to 10 M ２ / g and a particle size (VSSA) of 250-500 nm.

2. Specific surface area is 4 to 9 M ２ 10. The skin treatment preparation of claim 1, wherein the VSSA is 280-450 nm, specifically 300-430 nm.

3. 3. The skin treatment preparation of claim 1, wherein the molecular weight of the hyaluronic acid is 20 to 1500 KDa, specifically 50 to 1400 KDa, more specifically 100 to 1100 KDa, and even more specifically 300 to 1000 KDa.

4. 10. The skin treatment preparation of claim 1, wherein the activated smectite clay is montmorillonite, more specifically bentonite.

5. 10. The skin treatment preparation of claim 1, wherein the activated smectite clay is used in unmodified form.

6. 10. The skin treatment preparation of claim 1, wherein the activated smectite clay is modified with a fatty substance.

7. 7. The skin treatment preparation of claim 6, wherein the fatty substance is selected from the group consisting of oils and waxes of animal, vegetable or mineral origin, silicone oils, and mixtures thereof.

8. 10. A method of providing hyaluronic acid to the skin, wherein the hyaluronic acid comprises a portion of the hyaluronic acid-clay combination of claim 1.

9. Activated smectite clay having hyaluronic acid compounded therein, the hyaluronic acid-clay compound being 3-10M ２ The activated smectite clay has a non-pore specific surface area of ​​1000 nm / g and a particle size (VSSA) of 250-500 nm.

10. 10. A method for preparing the smectite clay-hyaluronic acid blend of claim 9, comprising incorporating hyaluronic acid into the clay under conditions of high shear.

11. 10. A method for enhancing feelings of well-being and positivity, comprising application of the skin treatment preparation of claim 1.

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