The disclosure relates to skin care compositions comprising one or more hydrophilic vitamins and a low-molecular weight hyaluronic acid or an alkali metal hyaluronate (<avg. 75 kDa) (e.g., avg. 35-avg. 60 kDA) (e.g., about avg. 50 kDA), as well as to methods of using and of making these compositions.
The efficient topical delivery of hydrophilic ingredients, including hydrophilic vitamins such as ascorbic acid (vitamin C), into the viable regions of the skin has long been a challenging task. For example, pure ascorbic acid is a very hydrophilic active and this can limit its transport through the lipid channels that separate the keratinocytes of the outermost stratum corneum, and which forms the main barrier to active delivery. While some hydrophilic vitamins can be “derivatized” in order to increase their hydrophobicity, and thereby become a more permeable alternative, these derivatives lack the proven efficacy of topically applied hydrophilic vitamins, such as ascorbic acid.
While skin care compositions are commonly used to deliver active ingredients, the effect may be transient or ineffective as active agents may not be able to permeate various layers of the skin. This challenge may be even more pronounced with various hydrophilic ingredients used as the topical active ingredients in a number of skin care compositions. Therefore, there is a need to enhance the topical delivery of hydrophilic ingredients, such as ascorbic acid, enabling efficient delivery to the viable regions of the skin past the protective barrier layers of the skin.
It has been surprisingly found that there is a specific molecular weight dependence of hyaluronic acid (“HA”) that can enhance and increase the depth of skin permeation of hydrophilic vitamins (e.g., ascorbic acid). At defined lower molecular weights (<average of 75 kDa) (e.g., average of 35 kDa-average of 60 kDA) (e.g., about average of 50 kDA) hyaluronic acid can have the effect of unexpectedly increasing the uptake and permeation of topical hydrophilic vitamins in the skin.
Hyaluronic acid (also called hyaluronan or hyaluronate), is an anionic, non-sulfated glycosaminoglycan (GAG) widely distributed throughout connective tissues of vertebrates, being the most abundant glycosaminoglycan of higher molecular weight in the extracellular matrix of soft periodontal tissues.
In one aspect the disclosure provides a skin care composition (Composition 1.0) comprising:
For example, the disclosure contemplates any of the following compositions (unless otherwise indicated, values are given as percentage of the overall weight of the composition):
The present disclosure provides, in another aspect, a skin care composition (Composition 2.0), e.g., skin care composition for use in inhibiting, treating or reducing damage to the skin caused reactive oxygen species. In one aspect, the skin care composition for use can be any of Composition 1.0 et seq.
The present disclosure provides, in another aspect, a method of inhibiting, treating or reducing damage to the skin caused reactive oxygen (Method 1.0), wherein the method comprises administering to a subject in need thereof an effective amount of any of Composition 1.0 et seq.
In another aspect, the present disclosure provides a method of depositing a topically active compound on the skin (Method 2.0), comprising applying an effective amount of any of skin care compositions disclosed herein, e.g., any of Compositions 1 et seq., to the skin.
In another aspect, the present disclosure provides a method selected from the following (Method 3.0):
In another aspect, the present disclosure provides a method selected from the following (Method 4.0):
In some embodiments, the skin care composition, e.g., any of Composition 1.0 et seq., comprises an oil selected from sunflower seed oil, olive oil, shear butter, jojoba oil, almond oil, grape seed oil, rose hip seed oil, mink oil, castor oil, soybean oil, mineral oil, and a combination thereof, optionally wherein the oil is sunflower seed oil.
In some embodiments, the skin care composition, e.g., any of Composition 1.0 et seq., comprises a thickener. In some embodiments, the thickener comprises a gum, optionally selected from xanthan gum, carrageenan and a combination thereof.
In some embodiments, the skin care composition, e.g., any of Composition 1.0 et seq., comprises a humectant, optionally wherein the humectant is selected from glycerin, sorbitol, and a combination thereof.
In some embodiments, the skin care composition, e.g., any of Composition 1.0 et seq., comprises water.
In some embodiments, the skin care composition, e.g., any of Composition 1.0 et seq., is free or substantially free of sulfate. In some cases, the skin care composition comprises about 4 wt. % or less, about 3 wt. % or less, about 2 wt. % or less, about 1 wt. % or less, about 0.5 wt. % or less, about 0.1 wt. % or less, based on the total weight of the skin care composition, of sulfate and/or sulfate based compound.
In some embodiments, the skin care composition, e.g., any of Composition 1.0 et seq., further comprises, a gelling agent, an additional antioxidant, a fragrance, or a combination thereof.
In some embodiments, the composition, e.g., any of Composition 1.0 et seq., is in the form selected from: a serum, a cream, a moisturizer, a mask, a cleanser, a facial make-up, and a balm (e.g., lip balm).
The composition of the present disclosure, e.g., any of Composition 1.0 et seq., may be any type of skin care composition. In certain embodiments, the composition is any composition that can be formulated into topical skin care formulations suitable for application to skin. Examples of such compositions include, but are not limited to: serums, creams, moisturizers, masks, cleanser (e.g., facial cleansers), a facial make-up, balms (e.g., lip balm), and cosmetics. The composition can comprise a single phase or can be a multi-phase system, for example a system comprising a polar phase and an oil phase, optionally in the form of a stable emulsion. In certain aspects, skin care compositions of the disclosure are formulated in a manner suitable for topically injection.
The compositions of the disclosure (e.g., any of Composition 1.0 et seq) can be liquid, semi-solid or solid. The formulation can be provided in any suitable container such as an aerosol can, tube or container with a porous cap, roll-on container, bottle, container with an open end, etc.
In some aspects, water may be present in the compositions of the disclosure, e.g., any of Composition 1.0 et seq. Water employed in the preparation of commercial skin care compositions should be deionized and free of organic impurities. When it is incorporated into the formulation, water can make up the balance of the compositions and includes about 10 to about 90 wt. %, or about 10 to about 80 wt. %, by weight of the skin care compositions. This amount of water includes the free water which is added plus that amount which is introduced with other materials such as glycerin, sorbitol, or any components of the disclosure.
In some embodiments, the skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., can include one or more pH adjusters. When incorporated in the formulation, the pH adjuster can include, but is not limited to, lactic acid, sodium hydroxide, and/or citric acid.
In some embodiments, the skin care compositions, e.g., any of Composition 1.0 et seq., may further comprise a betaine zwitterionic surfactant. In some aspects, the betaine zwitterionic surfactant may be a C8-C16 aminopropyl betaine, e.g., cocamidopropyl betaine.
In some embodiments, the skin care compositions described herein, e.g., any of Composition 1.0 et seq., may further comprises a non-ionic block copolymer is selected from Poloxamer 338, Poloxamer 407, Poloxamer, 237, Poloxamer, 217, Poloxamer 124, Poloxamer 184, Poloxamer 185, and a combination of two or more thereof.
As used herein, the term “effective amount” means the quantity of an active ingredient and/or skin care composition required to increase or enhance the uptake and permeation of one or more topical hydrophilic vitamins in the skin.
As used herein, “substantially free” of a material may refer to a composition where the material is present in an amount of less than 0.1 wt. %, less than 0.05 wt. %, less than 0.01 wt. %, less than 0.005 wt. %, less than 0.001 wt. %, or less than 0.0001 wt. %, based on a total weight of the skin care composition.
As used herein, “skin care composition” is meant to refer to a composition for which the intended use can include promotion or improvement of health, cleanliness, odor, appearance, or attractiveness of skin. For example, skin care compositions can include serum, a cream, a moisturizer, a mask, a cleanser, oil, salve, lotion, gel, ointment, paste, a facial make-up, a toner, an essence, and a balm (e.g., lip balm). Skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., can be applied topically to the skin by a user or consumer. In some aspects, skin care compositions of the disclosure can be applied by injection (e.g., subcutaneous or dermal injection). In certain aspects, skin care composition is intended to refer to a product for use at home or in a professional setting.
In certain aspects, the skin care compositions of the disclosure (e.g., any of Composition 1.0 et seq) can comprises one or more topically active compounds selected from: antibacterial agents, vitamins, medicaments, fragrance materials, antioxidants, other skin-care ingredients, and combinations of two or more thereof.
As used herein, unless otherwise specified, “Vitamin E” refers to a family of four isomers of tocopherols and four isomers of tocotrienols. All eight isomers of vitamin E have a 6-chromanol ring structure and a side chain. The four tocopherols include fully saturated side chains and include alpha-tocopherol, gamma-tocopherol, beta-tocopherol, and delta-tocopherol. The four tocotrienols include unsaturated side chains and include alpha-tocotrienol, gamma-tocotrienol, beta-tocotrienol, and delta-tocotrienol. As used herein, unless otherwise specified, the term “vitamin E” may refer to any one or more of the eight isomers. For example, as used herein, vitamin E may be or include one or more of alpha-tocopherol, gamma-tocopherol, beta-tocopherol, delta-tocopherol, alpha-tocotrienol, gamma-tocotrienol, beta-tocotrienol, delta-tocotrienol, or any combination thereof. In at least one implementation, the vitamin E includes at least one of the four tocopherols. It should be appreciated that the vitamin E and/or the isomers thereof may be or include natural forms of vitamin E, synthetic forms of vitamin E, or combinations thereof. Any one or more of the isomers of vitamin E may be in the “d” form, the “l” form, or combinations thereof. In some embodiments, vitamin E is vitamin E acetate or Vitamin E succinate. In some embodiments, vitamin E is vitamin E acetate.
As used herein, “Vitamin C” may be ascorbic acid or derivatives thereof. Ascorbic acid exists as two enantiomers commonly denoted “1” (for “levo”) and “d” (for “dextro”). The “1” isomer is the one most often encountered. Ascorbic acid is also referred to as L(+)-ascorbic acid or 1-ascorbic acid. The ascorbic acid derivatives may be or include, but are not limited to, L-ascorbic acid, calcium ascorbate, calcium 1-ascorbate dihydrate, magnesium ascorbate, potassium ascorbate, magnesium L-ascorbyl phosphate (also referred to as: magnesium ascorbate phosphate or ascorbic acid phosphate magnesium salt), L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, (+) sodium L-ascorbate, dehydro-1-(+)-ascorbic acid dimer, sodium ascorbyl phosphate (also referred to as: ascorbic acid phosphate sodium salt, sodium 1-ascorbyl phosphate, 2-phospho-L-ascorbic acid trisodium salt, L-ascorbic acid 2-phosphate trisodium salt or sodium L-ascorbyl-2-phosphate), ascorbic acid-2-glucoside, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl stearate, disodium ascorbyl sulfate, ascorbyl 6-palmitate, calcium ascorbyl phosphate, ascorbyl acetate, ascorbyl propionate, ascorbyl stearate, ascorbyl palmitate, ascorbyl dipalmitate, ascorbyl glucoside, ascorbic acid polypeptide, ethyl ascorbyl ether, ascorbyl ethyl silanol pectinate, or the like, or combinations thereof.
For example, the skin care composition includes a Vitamin C selected from ascorbyl glucoside, ascorbic acid-2-glucoside, ascorbyl acetate, and a combination of two or more thereof. In certain embodiments, the skin care composition comprises from ascorbyl glucoside, ascorbic acid-2-glucoside, or a combination thereof. In at least one embodiment, the one or more Vitamin C comprises ascorbyl glucoside.
The total amount of vitamin C, e.g., ascorbic acid or derivatives thereof, present in the skin care composition may be from about 0.1 to about 5 wt. %, based on the total weight of the skin care composition. For instance, the skin care composition may comprise a total amount of vitamin C from about 0.1 to about 5 wt. %, about 0.1 to about 4 wt. %, about 0.1 to about 3 wt. %, about 0.1 to about 2 wt. %, about 0.1 to about 1 wt. %, about 0.1 to about 0.7 wt. %; from about 0.3 to about 5 wt. %, about 0.3 to about 4 wt. %, about 0.3 to about 3 wt. %, about 0.1 to about 2 wt. %, about 0.3 to about 1 wt. %, about 0.3 to about 0.7 wt. %; from about 0.5 to about 5 wt. %, about 0.5 to about 4 wt. %, about 0.5 to about 3 wt. %, about 0.5 to about 2 wt. %, about 0.5 to about 1 wt. %, about 0.5 to about 0.7 wt. %; from about 0.7 to about 5 wt. %, about 0.7 to about 4 wt. %, about 0.7 to about 3 wt. %, about 0.7 to about 2 wt. %, about 0.7 to about 1 wt. %; from about 1 to about 5 wt. %, about 1 to about 4 wt. %, about 1 to about 3 wt. %, about 1 to about 2 wt. %, about 1 to about 1.5 wt. %, about 1 to about 1.25 wt. %; from about 1.25 to about 5 wt. %, about 1.25 to about 4 wt. %, about 1.25 to about 3 wt. %, about 1.25 to about 2 wt. %; from about 1.5 to about 5 wt. %, about 1.5 to about 4 wt. %, about 1.5 to about 3 wt. %, about 1.5 to about 2 wt. %; from about 2 to about 5 wt. %, about 2 to about 4 wt. %, about 2 to about 3 wt. %; from about 3 to about 5 wt. %, about 3 to about 4 wt. %, or any range or subrange thereof, based on the total weight of the skin care composition.
As used herein, “vitamin D” refers to a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. The two major forms are vitamin D2 or ergocalciferol, and vitamin D3 or cholecalciferol. Vitamin D includes vitamin D1 (mixture of molecular compounds of ergocalciferol with lumisterol), vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), vitamin D4 (22-dihydroergocalciferol), and vitamin D5 (sitocalciferol).
As used herein, “vitamin K” is a group of compounds with a common chemical structure of 2-methyl-1,4-naphthoquinone. Vitamin K plays a role in blood clotting, bone metabolism, and regulating blood calcium levels. Vitamin K includes vitamin K1 (phylloquinone) and vitamin K2 (menaquinone). Vitamin K2 have unsaturated isoprenyl side chains and are designated as MK-4 through MK-13, based on the length of their side chain.
Optional ingredients that may be included in the skin care composition of the invention include solvents; water-soluble alcohols such as C2-8 alcohols including ethanol; glycols including propylene glycol, dipropylene glycol, tripropylene glycol and mixtures thereof; glycerides including mono-, di- and triglycerides; medium to long chain organic acids, alcohols and esters; surfactants including emulsifying and dispersing agents; amino acids including glycine; structurants including thickeners and gelling agents, for example polymers, silicates and silicon dioxide; emollients; fragrances; and colorants including dyes and pigments.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally contain emollients in any desired amount to achieve a desired emollient effect. Emollients are known in the art and are used to impart a soothing effect on the skin. Non-volatile emollients are preferable. Classes of non-volatile emollients include non-silicone and silicone emollients, e.g., Poly silicone-11. Non-volatile, non-silicone emollients include C12-15 alkyl benzoate. The non-volatile silicone material can be a polyethersiloxane, polyalkyarylsiloxane or polyethersiloxane copolymer. An illustrative non-volatile silicone material is phenyl trimethicone or polymethylsilsesquioxane. Examples include, but are not limited to, PPG-14 butyl ether, PPG-3 myristyl ether, secondary alcohol ethoxylates, stearyl alcohol, stearic acid and salts thereof, glyceryl monoricinoleate, isobutyl palmitate, glyceryl monostearate, isocetyl stearate, sulphated tallow, oleyl alcohol, propylene glycol, isopropyl laurate, mink oil, sorbitan stearate, cetyl alcohol, hydrogenated castor oil, stearyl stearate, hydrogenated soy glycerides, isopropyl isostearate, hexyl laurate, dimethyl bras sylate, decyl oleate, diisopropyl adipate, n-dibutyl sebacate, diisopropyl sebacate, 2-ethyl hexyl palmitate, isononyl isononanoate, isodecyl isononanoate, isotridecyl isononanoate, 2-ethyl hexyl palmitate, 2-ethyl hexyl stearate, Di-(2-ethyl hexyl)adipate), Di-(2-ethyl hexyl)succinate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, octacosanol, butyl stearate, glyceryl monostearate, polyethylene glycols, oleic acid, triethylene glycol, lanolin, castor oil, sunflower seed oil, acetylated lanolin alcohols, acetylated lanolin, petrolatum, isopropyl ester of lanolin, fatty acids, mineral oils, butyl myristate, isostearic acid, palmitic acid, PEG-23 oleyl ether, olelyl oleate, isopropyl linoleate, cetyl lactate, lauryl lactate, myristyl lactate, quaternised hydroxy alkyl, aminogluconate, vegetable oils, isodecyl oleate, isostearyl neopentanoate, myristyl myristate, oleyl ethoxy myristate, diglycol stearate, ethylene glycol monostearate, myristyl stearate, isopropyl lanolate, paraffin waxes, glycyrrhizic acid, hydrocyethyl stearate amide. In some embodiments, the composition comprises an oil selected from sunflower seed oil, olive oil, shear butter, jojoba oil, almond oil, grape seed oil, rose hip seed oil, mink oil, castor oil, soybean oil, mineral oil, and a combination thereof. In certain embodiment, the composition comprises sunflower seed oil.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally include one or more humectants. Humectants can reduce evaporation and also contribute towards preservation by lowering water activity and can also impart desirable sweetness or flavor to compositions. Illustrative humectants may be or include, but are not limited to, glycerin, propylene glycol, polyethylene glycol, sorbitol, xylitol, or the like, or any mixture or combination thereof. In some embodiment, the humectant is selected from glycerin, sorbitol and a combination thereof. In certain embodiment, the humectant is glycerin.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally include thickeners. Illustrative thickeners may be or include, but are not limited to, colloidal silica, fumed silica, a cross-linked polyvinylpyrrolidone (PVP) polymer, cross-linked polyvinylpyrrolidone (PVP), or the like, or mixtures or combinations thereof. In some embodiments, the thickening system includes a cross-linked polyvinylpyrrolidone (PVP) polymer. Illustrative thickeners may also be or include, but are not limited to, carbomers (e.g., carboxyvinyl polymers), carrageenans (e.g., Irish moss, carrageenan, iota-carrageenan, etc.), high molecular weight polyethylene glycols, cellulosic polymers, hydroxyethylcellulose, carboxymethylcellulose, and salts thereof (e.g., CMC sodium), natural gums (e.g., karaya, xanthan, gum arabic, and tragacanth), colloidal magnesium aluminum silicate, or the like, or mixtures or combinations thereof. In some embodiments, the thickener comprises or is a gum, optionally selected from xanthan gum, carrageenan, and a combination thereof.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally include one or more gelling agents. Examples of gelling agents include, but are not limited to, waxes, esters of fatty acid and fatty alcohol, triglycerides, partially or fully hydrogenated soybean oil, partially or fully hydrogenated castor oil, other partial or fully hydrogenated plant oils, stearyl alcohol, or other cosmetically acceptable materials, which are solid or semi-solid at room temperature and provide a consistency suitable for application to the skin.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally have one or more antioxidants. For example, one or more antioxidants may be added to the composition to act as ingredient protectants and for maintenance of long-term stability of the composition. Examples of optional antioxidants include, but are not limited to citric acid, butylated hydroxytoluene, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally polymeric materials for thickening, such as polyamides, cellulose derivatives (e.g., hydroxypropylcellulose, hydroxypropyl methyl cellulose, etc.) and natural or synthetic gums, such as polyglycerides including agar, agarose, pectin, or guars or mixtures or combinations thereof. One class of materials worthy of attention for thickening a water-immiscible phase comprises derivatives of hydrolysed starch or other polysaccharides, including in particular esterified dextrins, such as dextrin palmitate. A further class of polymers that is particularly directed to structuring an oil phase containing a silicone oil comprises polysiloxane elastomers. Suspending agents such as silicas or clays such as bentonite, montmorillonite or hectorite, including those available under the trademark Bentone can also be employed to thicken liquid compositions according to the invention. The composition can be thickened with non-polymeric organic gellants, including selected dibenzylidene alditols (e.g., dibenzylidene sorbitol).
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may optionally include a fragrance. Any fragrance suitable for skin care use may be incorporated into the skin care composition of the disclosure. Fragrances tend to be relatively volatile aroma compounds which are capable of entering the gas phase at skin surface temperature.
The skin care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may be manufactured using methods known in the art. Typically, the ingredients are combined and optionally heated where components need to be melted. The components are mixed. Desirably, volatile materials such as fragrant materials are incorporated in the composition in the latter stages of a mixing cycle in order to avoid volatilization thereof. After mixing, the composition may be poured directly into the dispensers and the container capped to preserve the product until use.
To observe the uptake enhancement properties of various weights of hyaluronic acid, samples of porcine ear skin are first “pre-treated” with a 1% aqueous solution of the appropriate hyaluronic acid. Control samples are treated with water only. Following this pre-treatment, samples were then treated with a market-based skin care composition containing 20% by wt. of ascorbic acid and placed on a Franz cell (Logan Instruments, DHC-6T) for a 24-hour diffusion period. Following treatment, excess product was removed from the skin surface and the stratum corneum was removed from the skin via tape stripping twenty times. The remaining skin consists of the viable epidermis and the dermis layers, which were then homogenized and quantitatively analyzed for ascorbic acid content via an Agilent 1200 Series with UV-vis detector high performance liquid chromatography (HPLC). For each experiment, an “enhancement factor” was calculated for the viable skin regions. The “enhancement factor” is calculated as follows:
Enhancement Factor=100*(((penetrated ascorbic acid in samples pre-treated with HA)/(penetrated ascorbic acid in control samples only treated with water))−1)
This calculation allows for ease of comparison between the many different experiments that are conducted, the results of which are as follows:
Table 1 shows the enhancement factor for the various samples, each sample incorporating a different molecular weight HA or chemically modified HA.
Without being bound by theory, one of skill in the art may initially expect there to be a linear relationship where the samples receiving a treatment with a lower molecular weight HA would exhibit a greater enhancement of topical ascorbic acid delivery. And this expectation may be due to the potential for increased dermal absorption of lower molecular weight HA. However, as demonstrated by Table 1, the relationship is not linear. Surprisingly, the enhancement of topical ascorbic acid delivery was the highest using Sample C (˜50 kDa hyaluronic acid). Unexpectedly, both Sample A and Sample B both demonstrate decreased enhancement of ascorbic acid despite incorporating hyaluronic at average molecular weights of 3.6 kDa and 20 kDa, respectively, that were considerably lower than Sample C. Without being bound by theory, while lower molecular weight variants are believed to absorb more easily into the skin, it is possible that these lower molecular weight variants are also more prone to degradation which may limit their effectiveness. Alternatively, lower molecular weight hyaluronic acid may be less effective at absorbing water. Therefore, in order for the hyaluronic acid to enhance or effectively deliver ascorbic acid, the molecular weight must be low enough to readily absorb into the skin, but not so low that it is also prone to degradation and limited in its ability to absorb water.
Notably, the two samples treated with higher molecular weight HA, Samples D and E, both demonstrated a decreased ability to enhance the topical delivery of ascorbic acid. With respect to Sample E, the enhancement effect is actually negative. This should be interpreted to mean that samples pre-treated with the hyaluronic acid with an average molecular weight of 1,000-1,400 kDa have a reduced level of topical ascorbic acid delivery compared to the control samples that are pre-treated with only water. Visually, skin samples pre-treated with hyaluronic acid having an average molecular weight of 1,000-1,400 kDa appear to develop a film on their surface. Without being bound by theory, this observation could be because the molecular weight of the HA used in Sample E is so large that it is not absorbed into the skin and may simply remain on the skin surface to form a film. Again, without being bound by theory, this film forming effect may explain why Sample E demonstrates a negative value with respect to the topical delivery of ascorbic acid.
To further explore the possible mode of action of how HA enhances the topical delivery of ascorbic acid, Sample F is treated with average molecular weight 20 kDa acetylated hyaluronic acid. Although its low molecular weight of the acetylated hyaluronic acid suggests that it should readily absorb into the skin, without being bound by theory, it is possible that the partial capping of the polar hydroxyl groups with acetyl groups may significantly decrease the overall water binding abilities. As demonstrated in Table 1, similar to much larger molecular weight hyaluronic acid (e.g., Sample E), acetylated hyaluronic acid (having an average molecular weight of 20 kDa) also hinders the topical delivery of pure ascorbic acid even though the molecular weight of the acetylated hyaluronic acid is about 50 times lower than that used in Sample E. Again, without being bound by theory, this may indicate that the strong water binding ability of (non-acetylated) HA is critical in its ability to enhance the topical delivery of ascorbic acid. Moreover, it is clear from the range of molecular weight hyaluronic acid in Table 1 that the relationship with the delivery of ascorbic acid, and the molecular weight of the hyaluronic acid, is not linear. Again, without being bound by theory, it is possible that this unexpected relationship is due to hyaluronic acid with an average molecular weight of 50 kDa has a molecular weight that is low enough to be readily absorbed into the skin, and where the molecular weight is not so low that its water binding properties are greatly diminished.
The composition of the “market-based skin care composition” contained the following list of ingredients: Cyclopentasiloxane, Ascorbic Acid, Ethylhexyl Hydroxystearate, Polysilicone-11, Tocopherol, Isosorbide Dicaprylate, Polymethylsilsesquioxane, Hexylresorcinol, Silybum Marianum Fruit Extract, Hordeum Distichon (Barley) Extract, Citrus Aurantium Dulcis (Orange) Oil, Silica, Phellodendron Amurense Bark Extract, Santalum Album (Sandalwood) Wood Extract.
Ascorbyl glucoside is a derivative of ascorbic acid. However, it is believed that ascorbyl glucoside also has several properties that one of skill in the art may believe could impede its topical delivery into the skin. For example, compared to ascorbic acid, ascorbyl glucoside is both larger (MW of 338 g/mol for ascorbyl glucoside vs 176 g/mol for ascorbic acid) and more polar (Log P of −2.5 for ascorbyl glucoside vs Log P of −1.85 for ascorbic acid) and, thus, more hydrophilic.
The topical delivery of ascorbyl glucoside was carried out using the same experimental procedure as described in Example 1. Briefly, 20 wt. % of ascorbyl glucoside was loaded into the base formula of the “market-based skin care composition” described in Example 1, such that the ascorbyl glucoside containing skin care composition contained a total of 20 wt. % of ascorbyl glucoside relative to the total weight of the ascorbyl glucoside containing skin care composition. Note, however, that the active ingredients were removed from the market-based skin care composition, such that the ascorbyl glucoside containing skin care composition did not include ascorbic acid, tocopherol, hexylresorcinol or Silybum Marianum Fruit Extract.
Porcine ear skin explants were treated with either pure water (control) or a 1 wt. % aqueous solution of a hyaluronic acid (“HA”) with an average molecular weight of 50 kDa, wherein the solution contained 1 wt. % aqueous solution of a hyaluronic acid with the remainder being water. Subsequently, the skin pieces were treated with the ascorbyl glucoside containing skin care composition and then placed on a Franz diffusion cell for roughly 24 hours. Following this period, the top twenty layers of the skin were removed using adhesive tape strips. These tape strip layers, plus the remainder of the skin, were all analyzed for ascorbyl glucoside content using high performance liquid chromatography (HPLC).
The results of each trial with Sample G and Sample H can be seen in Table 2 and
The general observable trends were very similar to that seen for 20 wt. % pure ascorbic acid in an anhydrous base, used in Example 1, in which the skin sample was pre-treated with a 1 wt. % solution of hyaluronic acid having an average molecular weight of 50 kDa.
In summary, the results from Table 2 demonstrate that a 1 wt. % solution of hyaluronic acid having an average molecular weight of 50 kDa can significantly enhance the topical delivery of ascorbyl glucoside from a composition containing 20 wt. % of ascorbyl glucoside.
The topical delivery of carnosine was carried out using the same experimental procedure as described in Examples 1 and 2. Briefly, a carnosine composition was prepared by incorporating carnosine into the market-based skin care composition” described in Example 1 in an amount such that the carnosine composition contained 5 wt. % of carnosine relative to the total weight of the carnosine composition. The active ingredients were removed from the market-based skin care composition, such that the carnosine skin care composition did not include ascorbic acid, tocopherol, hexylresorcinol or Silybum Marianum Fruit Extract.
Porcine ear skin explants (Sample I), which was treated with an aqueous solution of 1 wt. % of hyaluronic acid having an average molecular weight of 50 kDa with the remainder being water and the carnosine composition, were prepared. A control (Sample J) was prepared by treating porcine ear skin explant with water and the carnosine composition. Specifically, the porcine ear skin explant received either aqueous solution of 1 wt. % of hyaluronic acid having an average molecular weight of 50 kDa with the remainder being water or the water before being treated with the carnosine composition.
After the carnosine composition was applied to the porcine ear skin explant, the porcine ear skin explant was placed on a Franz diffusion cell for roughly 24 hours. Following this period, the top twenty layers of the skin were removed using adhesive tape strips. These tape strip layers, plus the remainder of the skin, were all analyzed for carnosine content using high performance liquid chromatography (HPLC).
The results of the two trials, which evaluated the combination of the carnosine composition with the aqueous solution of a hyaluronic acid having an average molecular weight of 50 kDa as compared with the carnosine composition with water (control) can be seen in Table 3 (below) as well as in
The region demonstrating the highest amount of carnosine was the “skin remainder.” In both trials, there was a significantly higher level of carnosine in the skin samples subject to treatment with the 1 wt. % of hyaluronic acid solution (˜50 kDa) relative to the skin samples subject to treatment with only water.
The present disclosure has been described with reference to exemplary embodiments. Although a limited number of embodiments have been shown and described, it will be appreciated by those skilled in the art that changes may be made in these embodiments without departing from the principles and spirit of the preceding detailed description. It is intended that the present disclosure be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
A non-limiting example composition was prepared in accordance with aspects of the invention. The formulation for the exemplary composition is shown in Table 4 (below).
This application claims priority to U.S. Appl. No. 63/348,630, titled SKIN CARE COMPOSITIONS AND METHODS OF USE and filed Jun. 3, 2022, the content of which is incorporated herein by reference in its entirety for all purposes.
Number | Date | Country | |
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63348630 | Jun 2022 | US |