Skin care formulations using lipophilic peptides

Abstract

To provide a method of formulating a composition which resolves the solubility difficulties associated with lipophilic peptides such as Pal-GHK-Cu, while also largely avoiding the use of harsh solvents and alcohols.SOLUTION: According to an embodiment, a skin care formulation comprises a lipophilic peptide in a solution at a concentration of 0.2-1.1 wt.% based on the total weight of the formulation. The lipophilic peptide is solubilized in glycolipids at 1-6 wt.% based on the total weight of the formulation. The lipophilic peptide has a palmitoyl group.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention generally relates to the field of personal care formulations for the skin, and more specifically, to skin care compositions having a particularly high concentration of lipophilic peptides and methods for formulating said compositions.

Background Art

[0002] Peptides are short amino acid chains that occur naturally and have been found to be important in many cellular processes related to skin regeneration, including stimulation of collagen synthesis. It has also been established that many peptides penetrate the epidermal barrier when applied topically. In the past few years, many topical cosmetics containing peptides have been launched and advertised as having an anti-aging effect on the skin.

[0003] Copper tripeptide-1 (also called "GHK-Cu") is a small peptide consisting of three amino acids, namely glycine, histidine and lysine, and forms a complex with the physiologically beneficial mineral copper. GHK-Cu occurs naturally in the body and has been synthesized for use in cosmetics. GHK-Cu belongs to the matrikine peptide family and has been established as an active ingredient in skin care formulations. This peptide has been observed to improve skin elasticity and firmness, reduce wrinkles and enhance skin clarity. GHK-Cu is hydrophilic but has limited solubility and is usually formulated in cosmetic preparations in the form of a solution at a ratio of 0.02 - 0.1%.

[0004] Peptides of other categories, typically those with a palmitoyl group in the fatty acid side chain, have also been developed. Examples include palmitoyl pentapeptide-4, palmitoyl hexapeptide-12, and palmitoyl-lysyl-threonyl-threonyl-lysyl-serine. Peptides with palmitoyl chains are lipophilic and hydrophobic, and tend to exhibit superior delivery when crossing the epidermal barrier compared to free peptides. This is because palmitoylation creates sufficient hydrophobicity to provide a strong affinity to the cell membrane, promoting interaction with the lipid bilayer and localization of the peptide to the membrane surface. The palmitoyl group is thought to not only function as a lipid anchor but also to localize the peptide to a functional membrane subdomain. Therefore, palmitoylation enhances permeability and increases the effectiveness of the corresponding peptide.

[0005] The preferred peptide for use in formulations of this technology is palmitoyl-GHK-Cu ("Pal-GHK-Cu"), which combines the advantages of GHK-Cu peptides with palmitoyl side chains to make the peptide hydrophobic. Although Pal-GHK-Cu has been commercially available for several years, the inventors know that there are no medicinal cosmetic formulations marketed using this ingredient.

[0006] Typical methods in the art for solubilizing hydrophobic peptides likely involve the use of alcohols as solvents, such as methanol. However, alcohols and other typical solvents generally do not want to be included in large quantities in skincare formulations because they dry out the skin and negate the beneficial effects of the peptides. The lack of alcohol-free methods for solubilizing lipophilic peptides like Pal-GHK-Cu is likely the reason why they have not yet been commercially utilized in anti-aging skin formulations.

[0007] Similarly, most lipophilic peptides, including Pal-GHK-Cu, are difficult to incorporate into solutions at concentrations higher than approximately 0.02–0.1% of the final formulation. Above this concentration range, the formulation tends to become a peptide suspension rather than a solution. As with most topical medications, the active ingredient needs to be in solution for optimal absorption into the skin. Topical suspensions, compared to solutions, are generally less effective and slower in action because the solid peptide masses must first break down and decompose before being absorbed into the skin.

[0008] Furthermore, peptides are quite delicate molecules and are sensitive to degradation in solution. Therefore, formulations typically require the inclusion of a considerable amount of preservatives. However, large amounts of preservatives are known to disrupt the skin's natural microbiome, and some users have hypersensitivity or allergies to preservatives. Similarly, as consumers become more aware of foreign substances in personal care products, it is advantageous to formulate peptide-containing medicated cosmetics that maximize the proportion of active ingredients without adding excessive preservatives, while maintaining product shelf life and stability.

[0009] In this regard, it is desirable to provide a cosmetic formulation in which lipophilic peptides such as Pal-GHK-Cu are incorporated in solution form at concentrations higher than those normally available in the field, substantially free of harsh solvents or alcohols, and in which preservatives are optionally used in the formulation. [Overview of the project]

[0010] Novel cosmetic skincare compositions are currently under development that contain lipophilic peptides at a relatively high concentration, in the range of 0.2–1.1%, preferably at a level of 1.0%. These formulations do not involve the use of alcohol as a solvent, and preservatives are not required. Furthermore, the formulations constitute a peptide solution, rather than a suspension.

[0011] Preferred types of lipophilic peptides include those containing a palmitoyl group. A particularly preferred peptide for use in this technology is Pal-GHK-Cu. Furthermore, the formulations of this technology can be prepared using another lipophilic peptide, Pal-GHK.

[0012] The invention also provides a method for formulating compositions that solves solubility problems associated with lipophilic peptides such as Pal-GHK-Cu and significantly avoids the use of harsh solvents and alcohols.

[0013] Accordingly, one embodiment of the present disclosure provides a formulation comprising a lipophilic peptide incorporated in a solution at a level of 0.2 to 1.1%, preferably 1.0%.

[0014] Another embodiment of the present disclosure provides a formulation comprising a lipophilic peptide pre-dissolved in a glycolipid mixture, the formulation further comprising one or more additional cosmetic ingredients.

[0015] In another embodiment of the present disclosure, a formulation is provided which yields a gel formulation with low water activity and therefore no need to incorporate foreign preservatives, by combining a lipophilic peptide such as Pal-GHK-Cu with a glycolipid, and further combining it with additional oils and a sucrose base.

[0016] In a further embodiment of the present disclosure, a formulation is provided which a lipophilic peptide bound to a glycolipid and an additional skin conditioning active substance are bound together to form a transparent or translucent gel formulation that, when applied to the skin with body temperature-level heat, transforms into a substance having a creamy, skin-softening sensation.

[0017] In yet another embodiment of the present disclosure, a gel-like formulation is provided that combines a lipophilic peptide such as Pal-GHK-Cu or Pal-GHK bound to a glycolipid with a skin conditioning active substance, which is non-sensitizing and non-clogging, and is suitable as a skincare formulation.

[0018] In yet another further embodiment of the present disclosure, a method of formulating a skin care composition having at least one lipophilic peptide at a high concentration and substantially free of alcohol is provided.

[0019] In yet another further embodiment of the present disclosure, a method of formulating a skin care composition having at least one lipophilic peptide at a high concentration and substantially free of preservatives is provided.

[0020] This technology has many advantages. Current cosmetic compositions provide skin care formulations that contain very high levels of lipophilic and effective peptides that promote skin regeneration and thus result in a more youthful appearance. This peptide is further combined with many other skin care activators to increase the benefits to the skin. In the described base formulations, almost all of the ingredients used provide some benefit to the skin.

[0021] One embodiment and other embodiments of the present disclosure will become apparent from the following description.

Brief Description of the Drawings

[0022] [Figure 1] FIG. 1 represents the structure of Pal-GHK-Cu. [Figure 2] FIG. 2 represents an overview of the core process combining phases A, B, and C of a skin care formulation according to an embodiment of the present disclosure.

Modes for Carrying Out the Invention

[0023] Provided herein is a novel skin care formulation comprising a lipophilic peptide formulated at a concentration of about 10 times higher than the concentration achieved with a peptide solution when formulated in a cosmetic formulation, thereby increasing the level of the peptide for topical delivery to the epidermal cell layer of the user and promoting skin regeneration.

[0024] There are cosmetic formulations that can claim higher levels of lipophilic peptides than this range, but as far as the inventors know, they are peptides provided as suspensions, not in solution. Commercially available formulations with peptides formulated in solution rather than as suspensions are provided in the range of 0.02 - 0.1%. It is advantageous to completely solubilize the peptide, enabling a situation where it can immediately bring benefits to the skin without requiring further treatment prior to its action.

[0025] The formulation of this technology is substantially free of alcohols and other solvents such as methanol, pentylene glycol, propylene glycol, 1,3 - butanediol, triclosan, toluene, dimethyl isosorbide, and diethylene glycol monoethyl ether. The inclusion of preservatives is optional. When using Pal - GHK - Cu, the finished product becomes a transparent blue gel, which changes to a creamy emulsion when applied to the skin with body temperature added and is quickly absorbed by the skin without an oily or greasy feel. When using Pal - GHK, the formed gel is translucent and lacks blue color, but is otherwise the same as the above - mentioned transparent gel. In either case, it can be further suitably used as a commercial beauty product, having sufficient preservability and possessing both non - sensitizing and non - comedogenic properties.

[0026] A preferred type of lipophilic peptide for use with the described formulation method in the formulation of this technology is a palmitoylated peptide. A particularly preferred palmitoylated peptide is Pal - GHK - Cu, which has not been successfully formulated in any skin - care formulation known to the inventors so far. Pal - GHK is more widely used in various applications, but as far as the inventors know, it has never been used in solution up to levels exceeding 0.1% of the final formulation.

[0027] The structure of Pal - GHK - Cu is shown in Figure 1. GHK corresponds to a glycine - histidine - lysine peptide, and the C 30 , 51 H 51CuN6O5 can be represented as copper oxide (1-), [glycyl K NL-histidiny l- K N, K It is NN-(1-oxohexadecyl)-L-lysinato(3-).

[0028] The Pal-GHK-Cu used was provided as a blue powder by NEORE® Pharmaceutical Group Co., Ltd. While copper ions normally exist as green, they form a vivid blue color when complexed with the peptide, adding a visual advantage and appeal to the use of this particular peptide.

[0029] The Pal-GHK used was provided by NEORE Pharmaceutical Group Co., Ltd. This ingredient is a fine white powder.

[0030] The embodiments described herein will be explained below, but should not be interpreted restrictively. [Formulation Method]

[0031] To formulate the compositions of this technology, most industrial homogenizing mixers ("kettle") with the size and configuration for mixing personal care formulations are suitable. The kettle must have standard features such as a controllable internal sidewall scraper (also called a sweeper) separate from the homogenizing paddle, and the kettle also requires a valve at the bottom for taking test samples. The kettle should also be jacketed to allow for cooling of the internal temperature of the mixture as needed. The entire formulation process is carried out at room temperature, but the mixture in the kettle will typically heat up if mixing continues for a long time. Therefore, the mixture needs to be cooled to maintain room temperature inside the kettle, especially in the later stages of mixing. This is particularly important when handling delicate ingredients such as peptides.

[0032] The formulation of this technology can be prepared in three separate core phases (Phases A, B, and C), and as described later, any components can be added to some of the phases. If preservatives are included, a Phase D may be added. Figure 2 shows an overview of the core process combining Phases A, B, and C.

[0033] Unless otherwise specified, all amounts of each component are expressed as a weight percentage of the final product.

[0034] In Phase C, the lipophilic peptide becomes solubilized. As mentioned above, there are challenges in solubilizing lipophilic peptides without using alcohol, especially when higher concentrations are required. Several solubilizing agents were tried but were unsuccessful. However, the inventors found that glycolipid solutions showed high solubility of lipophilic peptides up to a level of 1.1%, yielding good results. This was surprising, as glycolipid solutions are generally recommended and used in foaming formulations such as toothpaste, cleansing foam, body wash, and shampoo. Foaming is not a desirable characteristic for peptide formulations, and it was not expected that glycolipid solutions would successfully solubilize powdered lipophilic peptides. However, the inventors found that glycolipids are effective in solubilizing powdered lipophilic peptides at relatively high concentrations.

[0035] After trying other solubilizers, the inventors succeeded in using a proprietary sucrose-derived glycolipid solution provided by EVONIK® Nutrition & Care GmbH, marketed under the brand name RHEANCEONE® (its INCI designation is "glycolipid"). This component is sold as a glycolipid solution (50% w / w), is alcohol-free, and is a low-viscosity, amber-colored liquid. It is initially added to the homogenizer in an amount that reaches 1–6% by weight in the final formulation. The preferred amount of glycolipid solution in the final formulation is in the range of 1.25–5%. The glycolipid solution is stirred at a rate of approximately 3,000 RPM for 20 minutes, followed by lateral sweeping using a sidewall scraper at a rate of 10 RPM. Such mixing rates have been found to provide adequate agitation without foaming and to adequately prepare the glycolipid solution to accept the dissolution of additional components.

[0036] After stirring for 20 minutes as described above, a lipophilic peptide such as Pal-GHK-Cu can be added to the glycolipid. Pal-GHK-Cu exists as a fine blue powder and is supplied by NEORE® Pharmaceutical Group Co., Ltd. The amount of Pal-GHK-Cu is supplied in such a quantity that a result level of 0.2–1.1% by weight can be achieved in the final formulation, which is a much higher percentage range compared to prior art formulations that incorporate up to 0.1% in solution. Higher levels of solubilization can be achieved when using a specific glycolipid mixture under the above conditions as a base for solubilizing this peptide. A preferred amount of Pal-GHK-Cu is 1% by weight in the final formulation.

[0037] When handling powdered peptides, it is crucial to visually confirm that all the powder is present and that no excess powder is adhering to the container walls, given the fine powder nature of the component. During the mixing process, it is necessary to periodically sample the glycolipid mixture containing the peptides from the bottom of the kettle, where undissolved solids tend to aggregate. This sampling process is called valve purging or bucket flipping. The sample should be centrifuged to confirm that it is completely dissolved.

[0038] Once the lipophilic peptides are sufficiently incorporated and the solution is confirmed to be homogeneous, this is typically stirred at 3000 RPM with a side-sweep speed of 10 RPM for 3–5 hours to complete Phase C. This can then be kept aside at a low RPM in the range of 500 RPM until it is ready to be mixed with Phases A and B described later.

[0039] For example, LUCAS MEYER COSMETICS® offers a suitable algal extract marketed under the trademark LANABLUE PARABEN FREE® ("Lanablue"), which is a mixture of Aphanizomenon flos-aquae var. flos aquae extract, water, a small amount of hydrolyzed starch (skin conditioner), phenoxyethanol (preservative), and potassium sorbate (preservative). Lanablue is advertised as a product that reduces the appearance of wrinkles and smooths the skin, using an algal extract that is said to have retinoid-like activity but without the side effects associated with retinoid use.

[0040] When using Lanablue, it can be successfully incorporated in the first step of Phase C by adding it to the mixing container simultaneously with the glycolipid. Next, Lanablue can be mixed into the solution using the same conditions as described above. The amount of Lanablue suitable for use in formulations of this technology may be in the range of 3–5% by weight in the final formulation. In the example formulation, an amount equivalent to 5% is used.

[0041] An additional optional skincare active ingredient that can be incorporated in Phase C is an extract from the root of the vetiver plant (also known as Vetiveria zizanioides, Chrysopogon zizanioides, Andropogon squarrosus, or Andropogon muricatus), a perennial herb native to India. Vetiver is used as a source of essential oil and in the production of high-end fragrances. In addition to its pleasant scent, vetiver root extract has been found to provide further benefits as a general skin conditioner, as it works to improve skin hydration, reduce wrinkles, and increase skin firmness. Suitable vetiver extract is supplied by GIVAUDAN® under the trademark VETIVYNE®. An amount equivalent to 1-3% by weight of VETIVYNE in the final formulation can be used effectively. The amount used in the example formulation corresponds to a final proportion of 3%.

[0042] When used, VETIVYNE can be incorporated into Phase C during a 20-minute block where the mixture is mixed at a side-sweep speed of 10 RPM and a mixing speed of 3000 RPM. The appropriate timing for adding VETIVYNE is approximately 10 minutes into the 20-minute mixing time.

[0043] Another optional component is a film-forming agent, which can be included at a level of up to 5% by weight. Film-forming agents are polymers often included in skincare formulations that form a continuous film on the skin surface, providing a protective layer and assisting in moisture retention. Many film-forming agents are available depending on the desired properties, such as flexibility, water repellency, retention, and permeability. Suitable film-forming agents for use in formulations of this technology include GLYCOFILM1.5P® (main component: biosaccharide gum-4) and FUCOGEL® powder (main component: biosaccharide gum-1), both of which are available from SOLABAI®. These film-forming agents are known to have a soothing effect on the skin and provide a smooth feel after application.

[0044] When using a film-forming agent in a formulation, as mentioned above, it can be incorporated into Phase C while stirring at 3000 RPM for 3 to 5 hours with a side sweep at 10 RPM after adding the lipophilic peptide.

[0045] Table 1 shows an example of a Phase C prescription. [Table 1]

[0046] Phase A of the composition contains thickening agents and emulsifiers to promote gel formation. While many options exist, a suitable and beneficial option was found to be SUCRAGEL XL®, marketed by ALFACHEMICALS®. SUCRAGEL XL is a mixture of ingredients that, in addition to acting as thickening agents and emulsifiers during formulation, also possess skincare benefits. SUCRAGEL XL consists of glycerin (emollient and moisturizer), caprylic and capric triglycerides (moisturizers and general skin conditioners), water, sucrose laurate, and sucrose stearate (both emollients and conditioners).

[0047] In Phase A, SUCRAGEL XL can be used in amounts ranging from 15% to 25% according to this technology. A preferred amount is 20%.

[0048] Phase A preparation involves adding SUCRAGEL XL to a mixing vessel and mixing at room temperature at a side-sweep speed of 10 RPM and 800-1000 RPM for 10 minutes. These conditions can be maintained while preparing Phase B. An example formulation for Phase A is shown in Table 2. [Table 2]

[0049] Phase B of this technology's composition contains other beneficial skin-active ingredients. Phase B contains an oily component, including MCT oil (medium-chain triglyceride, also known as caprylic / capric triglyceride or CCTG). Squalane is used to contribute to the base, and the additional active ingredient SYM3D® is used in Phase B.

[0050] Phase B can be prepared by adding MCT oil to a mixing vessel and incorporating further components, such as one or more oil-soluble active ingredients. The components are mixed at a rate of 3000 RPM at room temperature, followed by cyrosium evaporative mixing at 15 RPM. The sample is removed through a valve at the bottom of the kettle and tested by centrifugation, and the solution is visually inspected to confirm that the second component is completely dissolved. Centrifugation of the mixture sample is an optional step to confirm the complete dissolution of the second component.

[0051] The MCT oil used is, strictly speaking, an ester. It is a common ingredient in personal care formulations due to its effectiveness in skin conditioning. This product is available from many suppliers. The inventors used C-SYN-MCT®, sold by CUSTOM SYNTHESIS, LLC®. A suitable amount of MCT oil is used to reach a 10% level in the final formulation. Amounts ranging from 10% to 20% MCT oil can be used in the formulation.

[0052] One of the active ingredients in MTC oil is SYM3D (registered trademark), sold by SYMRISE AG (registered trademark). SYM3D is the trade name for dihydrodehydrodiisoeugenol, and its INCI name is hydroxymethoxyphenylpropylmethylmethoxybenzofuran. It is a hydrophobic white powder. SYMRISE claims that SYM3D promotes lipid uptake and accumulation in adipocytes, increasing lipogenesis and adipocyte size, ultimately resulting in youthful skin. SYM3D also has antioxidant properties.

[0053] The effective amount of SYM3D in the formulation of this technology is in the range of 0.1 to 1% by weight of the total formulation. The specific amount used by the inventors in the sample formulation was 0.5%. SYM3D is selectively soluble in certain oils. It can be solubilized in MTC oil under the conditions described above, but it cannot be soluble in squalane, for example. Therefore, it is important to use an oil component that is compatible with SYM3D, such as MTC oil.

[0054] Further ingredients that can be added to MTC oil before or after SYM3D include a sedative ingredient consisting of a mixture of bisabolol and hydroxymethoxyphenyldecanone, known as SYMRELIEF S®, sold by SYMRISE AG. This is an anti-irritant blend that also provides antioxidant activity, making it an even more beneficial ingredient for the skin. SYMRELIEF S can be incorporated in an amount of approximately 0.1% by weight when used. Many other sedatives are also available in the industry and can be used.

[0055] After adding an oil-soluble active ingredient to MTC oil and fully blending it, squalane purchased from NEOSSANCE®, a further oil phase component, was slowly added for 10 minutes at room temperature using only a side-sweep scraper at a speed of 25 RPM. Squalane is an effective emollient and moisturizer commonly used in skincare formulations. The inventors used it in amounts ranging from 55 to 60% of the total formulation, although lower amounts are also effective.

[0056] Table 3 shows an example of a Phase B prescription. [Table 3]

[0057] After preparing phases A, B, and C as described above, the phases can be combined as follows. First, slowly add phase B to phase A while stirring at 800-1000 RPM. At this time, the side-sweep scraper should be operated at a speed of 15 RPM. Add approximately 10% of phase B initially, and the mixture should be visually monitored to avoid pooling. After that, phase B can be gradually added while avoiding pooling. The speeds of the side sweep and homogenizer can be gradually increased to 50 RPM and 3000 RPM, respectively, while monitoring the mixing of phase B into phase A. As the level in the kettle rises, the viscosity increases and stirring becomes more difficult, so the rotation speed of the homogenizer should be gradually increased. Once the addition of phase B is complete, continue mixing at room temperature for 30 minutes with the side sweep and homogenizer at 50 RPM and 3000 RPM, respectively.

[0058] The next step is the addition of Phase C to the Phase A / B mixture. Phase C should be slowly incorporated into the Phase A / B mixture at a rate of approximately 10% of its volume at a time, while stirring with a side sweep of 50 RPM and a homogenizer speed of 3000 ROM. Once all of Phase C has been added, mixing at this rate should be continued at room temperature for 30 minutes. At this stage, it is important to activate the cooling jacket of the kettle to maintain the mixture at room temperature. As the mixture continues to stir and the homogenizer speed increases, the temperature inside the kettle tends to rise. Therefore, it is necessary to carefully monitor the room temperature level and cooling to avoid damaging the delicate peptides.

[0059] An optional Phase D may also be included in the process. Phase D may consist of an amount of preservative. A suitable preservative for use in the formulation is ISCAGUARD CPP®, a well-known cosmetic preservative available from ISCA UK®. ISCAGUARD CPP consists of chlorphenesin and phenoxyethanol and can be used in amounts ranging from 0.50%. Phase D may be added after Phase C is incorporated into Phases A / B, as described above.

[0060] Table 4 shows sample formulations for Phase D. [Table 4]

[0061] Figure 2 is a schematic diagram of the core phases A to C of the above manufacturing process.

[0062] Table 5 shows detailed prescription examples. [Table 5]

[0063] The formulation may further contain additional components, subject to their solubility in the formulation components. Such additional components may include cosmetic components that enhance or complement the lipophilic peptide formulation. In this specification, the term “cosmetic component” is used to refer to a product applied to the body (e.g., skin, hair, or nails) for the purpose of improving or enhancing some characteristic of the body, such as providing skincare effects. Therefore, additional cosmetic components may include conditioners, emollients, emulsifiers, humectants, plant extracts, natural oils, silicones, sunscreens, surfactants, and thickeners. Other examples of cosmetic ingredients include other peptides; amino acids (e.g., serine, lysine, proline, glycine, and glutamine); carbohydrates (e.g., ascorbyl glucoside, glucosyl hesperidin, and saccharide isomerates); proteins (e.g., collagen, elastin, and hydrolyzed lupin protein); lipids (e.g., ceramide, sphingoglycolipids, and phospholipids); vitamins (e.g., niacinamide, biotin, ascorbic acid, retinol, retinoic acid, and panthenol); sterols (e.g., phytosterol, zaclosterol, and 7-dehydrocholesterol); flavonoids (e.g., apigenin, hesperidin, and genistein); esters (methylsilanol mannuronate, butyl avocadoate, and jojoba esters); inorganic substances (e.g., kaolin, zinc, and magnesium); plant products (e.g., extracts of the fruit / leaf of Tasmannia Lanceolata, Curculigo Examples include extracts of orchioides roots and rose flora; and biotechnology products (e.g., Pseudoalteromonas exosaccharide, Alteromonas luminescent filtrate, and sodium hyaluronate).

[0064] Furthermore, formulations of this technology may also contain vitamins and their derivatives such as panthenol, ascorbic acid, niacinamide, and tocopherol; anti-inflammatory components such as allantoin, fetantriol, sphingosine, and bisabolol; other moisturizing components such as trimethylglycine and polyglutamic acid; antioxidant components such as flavonoids, xanthones, isoflavones, and alpha-lipoic acid; and anti-aging active components such as beta-glucan, alpha-hydroxy acid, and beta-hydroxy acid.

[0065] This preparation may contain fragrances such as essential oils, plant extracts, or synthetic fragrances. Examples include melon, vanilla, cucumber, aloe vera, almond, mango, coconut, cocoa butter, shea butter, linalool, citronellol, cinnamal, limonene, geraniol, eugenol, lavender oil, rose flower extract, bergamot oil, ylang-ylang oil, lemon, lime, orange, tangerine, peppermint, spearmint, and eucalyptus.

[0066] In this specification, the term "about" refers to an amount of 10% or less of the indicated amount, preferably 5% or less, which may be either more or less than the indicated amount.

[0067] Therefore, this technology corresponds to skincare formulations containing approximately 0.2–1.1% of lipophilic peptides in solution. Preferred lipophilic peptides for use in this technology are Pal-GHK-Cu and Pal-GHK. A particularly preferred amount of lipophilic peptide is 1%.

[0068] This technology also corresponds to a premix of lipophilic peptides in glycolipid solutions that do not contain alcohol or other harsh solvents, facilitating the dissolution of peptides at the concentrations mentioned above. The premix utilizes an amount of glycolipid such that the final formulation concentration is 1–6% by weight of glycolipid and 0.2–1.1% by weight of peptide. In the premix, these ranges correspond to a mixture of 3.2–52.4 w / w peptides dissolved in glycolipid. Particularly preferred are the amounts shown in the example formulations. If 1% peptide and 1.25% glycolipid are used in the premix constituting Phase A, this corresponds to 44% w / w peptide dissolved in glycolipid. If the Phase A premix contains 1% peptide and 5% glycolipid, this corresponds to 17% w / w peptide dissolved in glycolipid.

[0069] This technology also corresponds to skincare formulations containing the following as a weight percentage of the final formulation: (a) Contains a lipophilic peptide, preferably Pal-GHK-Cu or Pal-GHK, most preferably Pal-GHK-Cu, in an amount of 0.2 to 1.1%. (b) 1-6% of glycolipids. (c) A thickening agent in an amount of 15-25%. (d) 10.0-20.0% caprylic / capric triglyceride. (e) The rest is squalane. However, the sum of (a) to (e) must be 100.

[0070] This technology also corresponds to skincare formulations containing the following as a weight percentage of the final formulation: (a) A 1.0% amount of lipophilic peptide, preferably Pal-GHK-Cu. (b) Glycolipids in amounts of 1.25 to 5.00%. (c) A thickening agent in an amount of 20.00 to 21.57%. (d) 10.00% of caprylic / capric triglyceride. (e) 0.50% of an antioxidant, preferably hydroxymethoxyphenylpropylmethylmethoxybenzofuran. (f) Algae extract additive in an amount of 5.00%. (g) 3.00% vetiver extract additive. (h) The rest is squalane. However, the sum of (a) to (h) must be 100.

[0071] This technology also corresponds to skincare formulations containing the following as a weight percentage of the final formulation: (a) A 1.0% amount of lipophilic peptide, preferably Pal-GHK-Cu. (b) Glycolipids in amounts of 1.25 to 5.00%. (c) A thickening agent in an amount of 20.00 to 21.57%. Particularly preferred amounts are 20.00%, 20.57%, 21.45%, or 21.57%. (d) 10.00% of caprylic / capric triglyceride. (e) 0.50% of an antioxidant, preferably hydroxymethoxyphenylpropylmethylmethoxybenzofuran. (f) Algae extract additive in an amount of 5.00%. (g) 3.00% vetiver extract additive. (h) A sedative in an amount of 0.1-0.2%, preferably 0.10%. (i) A preservative in an amount of 0.1 to 1.0%, preferably 0.50%. (h) The rest is squalane. However, the sum of (a) to (h) must be 100.

[0072] This technology also corresponds to skincare formulations containing the following as a weight percentage of the final formulation: (a) A 1.0% amount of lipophilic peptide, preferably Pal-GHK-Cu. (b) A glycolipid in an amount of 1.25 to 5.00%, preferably 1.25%. (c) A thickening agent in an amount of 20.00 to 21.57%. Particularly preferred amounts are 20.57% or 21.45%. (d) 10.00% of caprylic / capric triglyceride. (e) 0.50% of an antioxidant, preferably hydroxymethoxyphenylpropylmethylmethoxybenzofuran. (f) Algae extract additive in an amount of 5.00%. (g) 3.00% vetiver extract additive. (h) A sedative in an amount of 0.1-0.2%, preferably 0.10%. (i) A film-forming agent in an amount of 0.1 to 5%, preferably 0.24 to 2.00%. (j) A preservative in an amount of 0.1 to 1.0%, preferably 0.50%. (k) The rest is squalane. However, the sum of (a) to (k) must be 100.

[0073] When a formulation is prepared according to the method described herein, a transparent blue oily gel is obtained when Pal-GHK-Cu is used, and a translucent oily gel is obtained when Pal-GHK is used. Because it contains peptides, which are delicate components that are sensitive to degradation by light, it is desirable to package it in opaque packaging such as an aluminum squeeze tube.

[0074] The product is used by taking an appropriate amount in your hand after washing your face and applying it directly to your skin. A key feature is that the gel transforms into a creamy consistency with the warmth of your hands, and when rubbed into the skin, it leaves no oily feeling. [Water activity test]

[0075] As shown in Table 5 and described above, the formulations of this technology consist primarily of skin-beneficial ingredients. These formulations also lack the usual requirements of extraneous preservatives such as triclosan, benzyl benzoate, methylisothiazolinone, or parabens. Generally, such preservatives are necessary to inhibit bacterial growth and prevent the degradation of delicate peptides incorporated into formulations. However, as detailed below, these formulations are composed as low-water-activity gels that do not require preservatives. This is highly beneficial, as it means the formulations can be composed almost entirely of skin-active and beneficial ingredients without using levels of preservatives that could interfere with the skin's biota or cause dryness or other adverse effects.

[0076] Water activity, expressed as Kw or Aw, is a standard measure used in personal care products to estimate shelf life and determine whether preservatives are needed. Water activity is not the same as water content. Rather, this test measures the bioavailability of water in response to biological reactions by microorganisms such as Gram-positive and Gram-negative bacteria, yeasts, or fungi. For reference, bone meal has a water activity of 0, while pure water has a water activity of 1.0.

[0077] In the cosmetics field, formulations with a water activity of less than 0.7 indicate that preservatives are not necessary.

[0078] The water activity of the formulation of this technology was measured using the AQUALAB® TDL, a standard water activity testing device. The water activity of the formulation was less than 0.65, indicating that the formulation does not require preservatives. This is a further advantage of providing this peptide formulation as a gel, which not only reduces water activity and eliminates the need for preservatives but also provides conditions that stabilize the delicate peptides contained therein. In the industry, most peptides are provided in serum form, which tends to have high water activity, sometimes requiring low-temperature storage conditions or the addition of large amounts of preservatives.

[0079] Please note that some ingredients suitable for optional incorporation into formulations of this technology contain small amounts of preservatives to protect the active ingredient. For example, LANABLUE, which uses algae extract as its active ingredient, also contains small amounts of the preservatives phenoxyethanol and potassium sorbate. However, since ingredients like those in LANABLUE are optional, it is possible to create a version without these ingredients.

[0080] The formulation may also be prepared to include added preservatives, such as ISCAGUARD CPP, which is present in some of the formulation examples. In any case, it may be beneficial to include a certain amount of preservative to further ensure that the formulation remains uncontaminated, despite its low water activity. However, the addition of preservatives is not mandatory.

[0081] The formulations of this technology also do not contain foreign alcohols or solvents, and certainly not at the levels typically required to dissolve lipophilic components such as the peptides used herein. However, certain optional components may themselves contain small amounts of alcohol. For example, VETIVYNE contains small amounts of propanediol. Here again, since VETIVYNE is an optional component, it is perfectly feasible to omit or substitute this component if a completely alcohol-free embodiment is to be prepared. [Other exams]

[0082] Formulations based on this technology are also considered non-sensitizing or irritating to the skin. A standard cosmetic patch test was conducted on 50 volunteers following an occlusive patch test protocol, in which the test product was applied and left in contact with the skin under an occlusive patch for 48 hours. No adverse events were observed. The mean irritation index level, an indicator of skin irritation and sensitization, was confirmed to be "NOT IRRITANT".

[0083] Standard stability tests were also conducted for formulations of this technology. Aliquots of the formulation were tested under conditions of 45°C, room temperature, 4°C, and -25°C, as well as under UV exposure. The test results showed a shelf life of 12 months under normal storage conditions, which is an acceptable period for such cosmetic formulations.

[0084] A standard comedone formation test involving 40 volunteers confirmed that this formulation is non-comedogenic.

[0085] Therefore, this technology has been confirmed to provide a high-concentration solution of lipophilic peptides in formulations that may be substantially free of preservatives and alcohols or other harsh solvents. The method described herein, in particular the method for solubilizing the lipophilic peptides to obtain high concentrations, is novel and results in formulations having approximately 10 times the peptide concentration compared to existing solutions, and having the benefits to the skin as described herein. This formulation is also useful as a cosmetic for the skin, is non-irritating and non-comedogenic, and has sufficient shelf life for commercial use.

[0086] Various embodiments of this disclosure have been described. These embodiments and other embodiments fall within the scope of the following claims.

Claims

1. Based on the total weight of the formulation, the solution contains 0.2 to 1.1% by weight of Pal-GHK-Cu. The Pal-GHK-Cu is solubilized in an amount of 1 to 6% by weight, based on the total weight of the formulation, using only a glycolipid solution derived from sucrose. Skin care formulation.

2. The skin care formulation according to claim 1, wherein the Pal-GHK-Cu is provided in an amount of 1%.

3. The skin care formulation according to claim 1, further comprising the following by weight based on the total weight of the formulation. (a) 15-25% thickener (b) 10.0–20.0% caprylic / capric triglyceride (c) Squalane q. s

4. The skin care formulation according to claim 3, further comprising the following by weight based on the total weight of the formulation. (a) 0.50% of antioxidant (b) Algae extract additive in an amount of 5.00% (c) 3.00% vetiver extract additive

5. The skin care formulation according to claim 4, wherein the antioxidant is hydroxymethoxyphenylpropylmethoxybenzofuran.

6. The skin care formulation according to claim 4, further comprising the following by weight based on the total weight of the formulation. (a) A sedative in an amount of 0.1-0.2% (b) Preservatives in an amount of 0.1 to 1.0%

7. The skincare formulation according to claim 6, provided below. (a) The sedative is provided in a 0.10% amount. (b) The preservative is provided in an amount of 0.50%.

8. The skincare formulation according to claim 1, wherein the water activity level (Aw) is 0.65 or less.

9. A mixture obtained by dissolving 3.2 to 52.4% (w / w) of Pal-GHK-Cu in only a glycolipid solution derived from sucrose.

10. The mixture according to claim 9, wherein the amount of Pal-GHK-Cu is 17 to 44%.

11. Use of the mixture of claim 9 or 10 for formulating a skincare composition.

12. A method for producing a skincare composition containing the following: (a) A mixture containing 17-44% (w / w) of the Pal-GHK-Cu in a glycolipid solution derived from sucrose is prepared to form the first component. (b) The thickener is stirred to form the second component. (c) Caprylic / capric triglyceride and squalane are mixed to form a third component. (d) The third component is combined with the second component under stirring to form the first combination. (e) The first component is combined with the first combination under stirring to form a skincare composition.

13. A method for producing the skincare composition according to claim 12, further comprising the following: (f) The skincare composition is combined with a preservative.

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