WO2025228150A1

WO2025228150A1 - Cosmetic composition and use thereof

Info

Publication number: WO2025228150A1
Application number: PCT/CN2025/089601
Authority: WO
Inventors: Yulan QU; Qianwen FAN; Jizong YAO; Huanjun ZHOU; Yuxin Chen; Kefeng TONG
Original assignee: ELC Management LLC
Current assignee: ELC Management LLC
Priority date: 2024-04-28
Filing date: 2025-04-17
Publication date: 2025-11-06
Anticipated expiration: 2026-10-28
Also published as: CN120837396A

Abstract

A cosmetic composition comprises at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate, for topical application to skin for seborrhea control.

Description

COSMETIC COMPOSITION AND USE THEREOF

FIELD OF THE DISCLOSURE

The present disclosure relates to the field of cosmetic and/or dermatologic composition. Particularly, the present disclosure is directed to a cosmetic and/or dermatological composition for topical application.

BACKGROUND ART

Seborrhea, or oily skin is a common cosmetic or dermatological problem that occurs when oversized sebaceous glands produce excessive amounts of sebum, giving the appearance of shiny and greasy skin, as well as visible skin pores and acne.

Lipogenesis inhibition is one of the major pathways contributing to effective seborrhea control. And in in vitro studies, Oil red or Nile-red staining are commonly used methods to evaluate active’s effect on lipogenesis. For example, Isotretinoin, one of the well-known compounds for seborrhea control, was reported to reduce lipogenesis in sebocytes (Cemil, B. C., et al., 2016) .

Pharmacological downregulation of IGF-I is another promising strategy in the treatment of acne vulgaris. Epigallocatechin-3-gallate (EGCG) , the main polyphenolic fraction of green tea, was found showing clinical efficacy as an acne therapeutic agent through anti-IGF-I effects. It could inhibit lipogenesis and cell proliferation induced by IGF-1 (Im, M., et al., 2012) .

Thus, excess oil is cosmetically and dermatologically undesirable and seborrhea control is a most challenging and effective approach to improve oily skin conditions. It is possible to recover skin physiology balance and address skin problems such as acne, seborrhea, conspicuous pores, and the like by inhibiting excessive sebum production.

EP3334403A1 discloses a topical composition comprising Prunus mume leaf extract, encapsulated resveratrol, oligopeptide-1, and niacinamide, and optionally one or more of Opuntia tuna fruit extract, malachite extract and/or adenosine, wherein the topical composition can reduce sebum secretion of skin.

CN105193659A discloses an aloetic oil control and acne removal composition comprising Aloe vera extract, Laminaria Saccharina extract and the like, wherein the composition utilizes natural plant extracts to achieve oil-control effect and significantly reduces sebum secretion with a long lasting effect.

The existing seborrhea control technologies usually utilize chemicals or natural extracts to achieve the effects of reducing sebum secretion. There is still a need for the technologies to achieve seborrhea control in a more efficient way.

SUMMARY

The present invention is based on the finding that a combination of at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate unexpectedly shows synergistic lipogenesis inhibition efficacy in sebocytes. Such a combination further inhibits lipogenesis process compared to the sebosuppressive effect achieved by using any one of the actives alone. This enables the provision of a superior solution for skin seborrhea control and comedones prevention, particularly in cosmetic or dermatological applications.

Therefore, the present disclosure aims to provide a seborrhea control technology which can achieve the inhibition of lipogenesis in a more efficient way.

The inventors have now discovered that the object of the present disclosure can be achieved by the following aspects.

In one aspect, the present disclosure provides a cosmetic composition comprising at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate.

According to an embodiment, the Laminaria extract is selected from Laminaria Saccharina extract (LS extract) , Laminaria Digitata extract (LD extract) , Laminaria Ochroleuca extract (LO extract) , Laminaria Algae extract (LA extract) , and mixtures thereof. According to a preferable embodiment, the Laminaria extract is Laminaria Saccharina extract.

According to an embodiment, the salt of hydrolyzed hyaluronate is selected from Hydrolyzed Zinc Hyaluronate (miniHA-Zn) , Hydrolyzed Potassium Hyaluronate (miniHA-K) , Hydrolyzed Calcium Hyaluronate (miniHA-Ca) , and mixtures thereof. According to a preferable embodiment, the salt of hydrolyzed hyaluronate is Hydrolyzed Zinc Hyaluronate.

According to an embodiment, the cosmetic composition has a weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate equal to or above 1: 100. According to a preferable embodiment, the cosmetic composition has a weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate from about 1: 10 to about 500: 1. According to a more preferable embodiment, the cosmetic composition has a weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate from about 1: 2 to about 100: 1. According to a particularly preferable embodiment, the cosmetic composition has a weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate from about 1: 1 to about 40: 1.

According to an embodiment, based on the total weight of the cosmetic composition, the Laminaria extract is present in the cosmetic composition in an amount of from about 0.0005%to about 5%by weight (on dry weight basis) . According to a preferable embodiment, based on the total weight of the cosmetic composition, the Laminaria extract is present in the cosmetic composition in an amount of from about 0.0008%to about 1%by weight (on dry weight basis) . According to a more preferable embodiment, based on the total weight of the cosmetic composition, the Laminaria extract is present in the cosmetic composition in an amount of from about 0.001%to about 0.1%by weight (on dry weight basis) .

According to an embodiment, based on the total weight of the cosmetic composition, the salt of hydrolyzed hyaluronate is present in the cosmetic composition in an amount of from about 0.0001%to about 5%by weight. According to a preferable embodiment, based on the total weight of the cosmetic composition, the salt of hydrolyzed hyaluronate is present in the cosmetic composition in an amount of from about 0.0002%to about 1%by weight. According to a more preferable embodiment, based on the total weight of the cosmetic composition, the salt of hydrolyzed hyaluronate is present in the cosmetic composition in an amount of from about 0.001%to about 0.05%by weight.

According to an embodiment, the cosmetic composition comprises from about 0.001%to about 0.1%by weight (on dry weight basis) of Laminaria Saccharina extract and from about 0.001%to about 0.05%by weight of Hydrolyzed Zinc Hyaluronate, and wherein the weight ratio between Laminaria Saccharina extract and Hydrolyzed Zinc Hyaluronate is in a range of from about 1: 1 to about 40: 1

According to an embodiment, the cosmetic composition further comprises at least one of active ingredients selected from sugar derivatives, natural extracts, ferments, vitamins, urea, caffeine, salicylic acid and its derivatives, alpha-hydorxy acids and their derivatives, retinoids, niacinamide, humectants, sunscreens, essential oils of mint, aloe vera or ginseng, and mixtures thereof.

In another aspect, the present disclosure provides a method for manufacturing the cosmetic composition according to the present disclosure, comprising:

a. adding at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate into an aqueous solvent to form a water phase;

b. homogenizing the water phase at room temperature to form a clear solution; and

c. continuing to homogenize the solution for 10-30 mins to obtain the cosmetic composition.

In yet another aspect, the present disclosure provides a cosmetic product for seborrhea control comprising the cosmetic composition according to the present disclosure.

In yet another aspect, the present disclosure provides non-therapeutic use of the cosmetic composition according to the present disclosure for seborrhea control.

In yet another aspect, the present disclosure provides a non-therapeutic method for seborrhea control, comprising topically applying the cosmetic composition or the cosmetic product according to the present disclosure to skin in need thereof.

Other features and advantages of the present disclosure will emerge more clearly on reading the description and the examples that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of this disclosure, reference is now made to the following description, taken in conjunction with the accompanying drawing, in which:

FIGURE 1 is a histogram showing the lipogenesis inhibition effect of the active a (LS extract) and the active b (miniHA-Zn) used individually or in combination at different concentrations (LS extract at 0.00475%; miniHA-Zn at 0.002%and 0.004%) .

FIGURE 2 is a histogram showing the lipogenesis inhibition effect of the active a (LS extract) and the active b (miniHA-Zn) used individually or in combination at different concentrations (LS extract at 0.0095%and 0.019%; miniHA-Zn at 0.001%, 0.002%, and 0.008%) .

DETAILED DESCRIPTION

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art the present disclosure belongs to. When the definition of a term in the present description conflicts with the meaning as commonly understood by those skilled in the art the present disclosure belongs to, the definition described herein shall apply.

Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of components and/or conditions are to be understood as being modified in all instances by the term "about" with conventionally known meaning in the art, e.g., within 10%of the indicated number (e.g., "about 10%" means 9%-11 %and "about 2%" means 1.8%-2.2%) .

Further, the ranges stated in this disclosure and the claims are intended to include the entire range specifically and not just the endpoint (s) . For example, a range stated to be 0 to 10 is intended to disclose all whole numbers between 0 and 10 such as, for example 1, 2, 3, 4 and any sub ranges formed by any two values thereof, etc., all fractional numbers between 0 and 10, for example 1.5, 2.3, 4.57, 6.1113 and any sub ranges formed by any two values thereof, etc., and the endpoints 0 and 10.

As used herein, the term "room temperature" means a temperature of about 20-25℃. All parts or percentages in the present disclosure refer to weight parts or weight percentages, unless otherwise specified.

According to the first aspect, the present disclosure is concerned with a cosmetic composition comprising at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate. According to an embodiment, the cosmetic composition of present disclosure is used for topical application to skin for seborrhea control and/or comedones prevention.

Laminaria extract

According to the first aspect, the cosmetic composition of the present disclosure comprises at least one Laminaria extract.

The Laminaria extract suitable for the cosmetic composition according to the present disclosure may be selected from Laminaria Saccharina extract, Laminaria Digitata extract, Laminaria Ochroleuca extract, Laminaria Algae extract, and mixtures thereof. Preferably, the Laminaria extract used in the cosmetic composition of the present disclosure is Laminaria Saccharina extract.

The cosmetic composition of the present disclosure may comprise a safe and effective amount of Laminaria Saccharina extract, a brown algae extract. One example of Laminaria Saccharina extract is sold under the tradename Phlorogine and/or Phlorogine BG by Biotech Marine (Seppic) , France. Another suitable Laminaria Saccharina extract is available via product code HG 657 from Ennagram, France. Phlorogine is known as anti-seborrhoeic agent that can regulate the activity of sebaceous glands, as described for example in US Application Publication No. 2008/0119527A1. Extraction methods for brown algae are also known. European Patent No. 1074262B1 describes an extraction method for the class Phaeophyceae and the species Laminaria Ochroleuca. These extracts are described as being used in cosmetic compositions as an osmoprotector, free-radical scavenger, or against of skin aging effects. The commercially available Laminaria Saccharina extract may include other compounds, such as, for example water, thickeners, humectants, solvents and solubilizers, etc. For example, Phlorogine and/or Phlorogine BG contain approximately about 1%to about 2.5%dry extract (i.e., the pure Laminaria Saccharina extract) with the remaining material being inert carrier.

The cosmetic composition of the present disclosure may comprise at least one Laminaria extract in an amount of from about 0.0005%to about 5%by weight, in one embodiment from about 0.0008%to about 1%by weight, in another embodiment from about 0.001%to about 0.1%by weight (on dry weight basis) , based on the total weight of the cosmetic composition. For example, based on the total weight of the cosmetic composition, the Laminaria extract may be present in the cosmetic composition in an amount of about 0.0005%, about 0.0006%, about 0.0007%, about 0.0008%, about 0.0009%, about 0.001%, about 0.005%, about 0.01%, about 0.0125%, about 0.025%, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%by weight (on dry weight basis) .

The Laminaria extract used in an appropriate amount contributes to skin benefits such as moisturizing, skin-soothing, regulation in the activity of sebaceous glands, anti-aging skin, etc. When used in combination with at least one salt of hydrolyzed hyaluronate, it in particular exhibits a synergistic effect in terms of lipogenesis inhibition, consequently allowing access to a promising seborrhea control application.

Salt of hydrolyzed hyaluronate

According to the first aspect, the cosmetic composition of the present disclosure comprises at least one salt of hydrolyzed hyaluronate.

Salts of hydrolyzed hyaluronate are salts derived from Hyaluronic Acid. Hyaluronic Acid (CAS No. 9004-61-9; Structural Formula 1) is a linear glycosaminoglycan composed of repeating disaccharides of β4-glucuronic acid-β3-N-acetylglucosamine with molecular formula of (C₁₄H₂₁NO₁₁) _n. Hyaluronic Acid is a water-soluble substance that is available as a highly purified, freeze-dried powder or aqueous solution. Hyaluronic Acid may also be presented as its potassium or sodium salt (i.e., Potassium Hyaluronate or Sodium Hyaluronate) . The molecular weight (MW) of Hyaluronic Acid in cosmetics is highly variable and ranges from 5 -1800 kiloDaltons (kDa) , dependent upon manufacturing procedures. Hyaluronic Acid has a high capacity for water retention.

Structural Formula 1: Hyaluronates (when R is hydrogen = Hyaluronic Acid; when R is metal cation = metal salt of Hyaluronate)

Hyaluronates with different molecular weights has different physical and biological properties. Among them, low molecular weight hyaluronate, also called hydrolyzed hyaluronate (miniHA) , refers to hyaluronate with a molecular weight of no more than 1000 kDa (1 MDa) . The molecular size of miniHA is too small to provide comparable lubricity to medium-to-high molecular weight hyaluronate, but it has more biological activities. The results of a series of experiments in vitro and in vivo showed that miniHA has significant effects of deep moisturizing, repairing cells damaged by UV, scavenging free radical and anti-aging. Moreover, miniHA has good transdermal absorption compared with common HA, and thus has active efficacies in the epidermis even dermis, so it can be applied in hydrating, repairing and anti-aging products.

Preferably, the salt of hydrolyzed hyaluronate suitable for the cosmetic composition according to the present disclosure may be selected from Hydrolyzed Zinc Hyaluronate (miniHA-Zn) , Hydrolyzed Potassium Hyaluronate (miniHA-K) , Hydrolyzed Calcium Hyaluronate (miniHA-Ca) and mixtures thereof. More preferably, the salt of hydrolyzed hyaluronate used in the cosmetic composition of the present disclosure is Hydrolyzed Zinc Hyaluronate.

Hydrolyzed Zinc Hyaluronate is the hydrolysate of Zinc Hyaluronate (CAS No. 88103-59-7) derived by acid, enzyme, or other method of hydrolysis, also referred to as Zinc Hydrolyzed Hyaluronate. Generally, miniHA-Zn is obtained by exchanging sodium ions in Hydrolyzed Sodium Hyaluronate and zinc ions in zinc salts. As a commercial product of Hydrolyzed Zinc Hyaluronate, mention may be made, for example, of the product sold under the tradename "Hybloom^TM" by Bloomage Biotechnology Co. Ltd. MiniHA-Zn has functions such as moisturizing, inhibiting harmful skin bacteria, anti-inflammatory, preventing skin wound infection, repairing damage, controlling oil, anti-aging, antioxidant, and removing fine lines, maintains a healthy skin (including scalp) ecological environment.

Preferably, the salt of hydrolyzed hyaluronate suitable for the cosmetic composition according to the present disclosure has a molecular weight of no more than 1 MDa, preferably from 5 kDa to 500 kDa, more preferably from 100 kDa to 300 kDa, such as 1 kDa-5 kDa, 5 kDa-10 kDa, 10 kDa-200 kDa, 200 kDa-500 kDa, 500 kDa-1000 kDa.

The cosmetic composition of the present disclosure may comprise at least one salt of hydrolyzed hyaluronate in an amount of from about 0.0001%to about 5%by weight, in one embodiment from about 0.0002%to about 1%by weight, in another embodiment from about 0.001%to about 0.05%by weight, based on the total weight of the cosmetic composition. For example, based on the total weight of the cosmetic composition, the salt of hydrolyzed hyaluronate may be present in the cosmetic composition in an amount of about 0.0001%, 0.0002%, about 0.0003%, about 0.0004%, about 0.0005%, about 0.0006%, about 0.0007%, about 0.0008%, about 0.0009%, about 0.001%, about 0.002%, about 0.005%, about 0.01%, about 0.02%, about 0.05%, about 0.1%, about 0.2%, about 0.5%, about 1%, about 1.5%, about 2%, about 3%, about 4%, about 5%by weight.

The salt of hydrolyzed hyaluronate used in an appropriate amount contributes to an improvement in the condition and appearance of skin, more particularly to skin moisturizing, oil control, cleansing, soothing, anti-oxidation, anti-bacteria, photo-protecting, damage repairing, an improvement in the skin barrier function, etc. When used in combination with at least one Laminaria extract, it in particular exhibits a synergistic effect in terms of lipogenesis inhibition, consequently allowing access to a promising seborrhea control application.

Without wishing to be bound by any particular theory, it is believed that both of the Laminaria extract and the specific salt of hydrolyzed hyaluronate exhibit moderate but not outstanding seborrhea control properties. The present inventors surprisingly found that the combination of at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate shows synergistic lipogenesis inhibition efficacy which is substantially superior to the additive sebosuppressive effects achieved by using either one of the actives alone. This enables the provision of a more effective solution for skin seborrhea control and/or comedones prevention, particularly in cosmetic or dermatological applications.

The cosmetic composition of the present disclosure may have a weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate equal to or above 1: 100, preferably, from about 1: 10 to about 500: 1, more preferably, from about 1: 2 to about 100: 1, and particularly preferably, from about 1: 1 to about 40: 1. For example, the weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate in the cosmetic composition is about 1: 100, 1: 90, 1: 80, 1: 70, 1: 60, 1: 50, 1: 40, 1: 30, 1: 20, 1: 15, 1: 10, 1: 9, 1: 8, 1: 7, 1: 6, 1: 5, 1: 4, 1: 3, 1: 2, 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 6: 1, 7: 1, 8: 1, 9: 1, 10: 1, 15: 1, 20: 1, 30: 1, 40: 1, 50: 1, 60: 1, 70: 1, 80: 1, 90: 1, 100: 1, 150: 1, 200: 1, 250: 1, 300: 1, 350: 1, 400: 1, 450: 1, 500: 1.

An appropriate ratio between Laminaria extract and salt of hydrolyzed hyaluronate contributes to a substantial synergistic effect in terms of lipogenesis inhibition, consequently allowing access to a promising seborrhea control application.

Additional Ingredients

The cosmetic compositions of the present disclosure may be in form of solid, semi-solid, or liquid, and may be in the solution, emulsion, suspension, or anhydrous form. If in the solution or suspension form, the cosmetic composition of the present disclosure may advantageously comprise water in an amount of no more than 98%by weight, for example, from 25%to 95%by weight, from 30%to 90%by weight, or from 35%to 85%by weight, relative to the total weight of the composition. If in the emulsion form, the cosmetic composition of the present disclosure may comprise water in amount of from 5 wt. %to 90 wt. %, or from 10 wt. %to 80 wt. %and oil in amount of from 5 wt. %to 90 wt. %, or from 10 wt. %to 75 wt. %, relative to the total weight of the composition. If in the anhydrous form, the cosmetic composition of the present disclosure may comprise oil in amount of from 10 wt. %to 99 wt. %and solidifying agents in amount of from 10 wt. %to 99 wt. %, relative to the total weight of the composition.

As long as the object of the present disclosure can be achieved, the cosmetic composition may also comprise at least one cosmetically acceptable active ingredient, such as sugar derivatives, natural extracts, ferments, vitamins, urea, caffeine, salicylic acid and its derivatives, alpha-hydorxy acids and their derivatives, retinoids, niacinamide, humectants, sunscreens, essential oils of mint, aloe vera or ginseng, in particular for preventing or reducing excessive sebum, acne, wrinkles, lines, dry skin, photoaging, and inflammation. Other cosmetically acceptable ingredient that may be mentioned include antioxidants, fatty substances/oils, thickeners, softeners, emulsifiers, sunscreens, antifoaming agents, moisturizers, fragrances, surfactants, fillers, sequestering agents, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants, pigments or nanopigments, or any other ingredients usually formulated into cosmetics or medicaments. Non-limiting examples of some of these ingredients are provided in the following subsections.

A. Humectants

The composition of the present disclosure may contain one or more humectants. If present, they may range from about 0.1%to 75%, preferably from about 0.2%to 70%, more preferably from about 0.5%to 40%by weight of the total composition. Examples of suitable humectants include glycols, sugars, and the like. Suitable glycols are in monomeric or polymeric form and include polyethylene and polypropylene glycols such as PEG 4-10, which are polyethylene glycols having from 4 to 10 repeating ethylene oxide units; as well as C_1-6 alkylene glycols such as propylene glycol, butylene glycol, pentylene glycol, and the like. Suitable sugars, some of which are also polyhydric alcohols, are also suitable humectants. Examples of such sugars include glucose, fructose, honey, hydrogenated honey, inositol, maltose, mannitol, maltitol, sorbitol, sucrose, xylitol, xylose, and so on. Also suitable is urea. Preferably, the humectants used in the composition of the present disclosure are C_1-6, preferably C_2-4 alkylene glycols, most particularly butylene glycol.

B. Botanical Extracts

The composition of the present disclosure may contain one or more botanical extracts in additional to the Laminaria extract. If present, suggested ranges are from about 0.0001%to 20%, preferably from about 0.0005%to 15%, more preferably from about 0.001%to 10%by weight of the total composition. Suitable botanical extracts include extracts from plants (herbs, roots, flowers, fruits, seeds) such as flowers, fruits, vegetables, and so on, including yeast ferment extract, Padina pavonica extract, Thermus thermophilis ferment extract, Camelina sativa seed oil, Boswellia serrata extract, olive extract, Acacia dealbata extract, Acer saccharinum (sugar maple) , Acidopholus, Acorus, Aesculus, Agaricus, Agave, Agrimonia, algae, aloe, citrus, Brassica, cinnamon, orange, apple, blueberry, cranberry, peach, pear, lemon, lime, pea, seaweed, caffeine, green tea, chamomile, willowbark, mulberry, poppy, and those set forth on pages 1646 through 1660 of the CTFA Cosmetic Ingredient Handbook, Eighth Edition, Volume 2. Further specific examples include, but are not limited to, Glycyrrhiza glabra, Salix nigra, Macrocycstis pyrifera, Pyrus malus, Saxifraga sarmentosa, Vitis vinifera, Morus nigra, Scutellaria baicalensis, Anthemis nobilis, Salvia sclarea, Rosmarinus officianalis, Citrus limonum, Panax ginseng, Siegesbeckia orientalis, Fructus mume, Ascophyllum nodosum, Glycine soja extract, Beta vulgaris, Haberlea rhodopensis, Polygonum cuspidatum, Citrus aurantium dulcis, Vitis vinifera, Selaginella tamariscina, Humulus lupulus, Citrus reticulata Peel, Punica granatum, Asparagopsis, Curcuma longa, Menyanthes trifoliata, Helianthus annuus, Hordeum vulgare, Cucumis sativus, Evernia prunastri, Evernia furfuracea, Kola acuminata, and mixtures thereof.

C. Surfactants

The composition of the present disclosure may contain one or more surfactants, especially if in the emulsion form. However, such surfactants may be used if the compositions are solutions, suspensions, or anhydrous also. If present, the surfactant may range from about 0.001%to 30%, preferably from about 0.005%to 25%, more preferably from about 0.1%to 20%by weight of the total composition. Suitable surfactants may be silicone or organic, nonionic, cationic, anionic, amphoteric or zwitterionic.

Suitable nonionic surfactants include alkoxylated alcohols or ethers, formed by the reaction of an alcohol with an alkylene oxide, usually ethylene or propylene oxide. Suitable alcohols include mono-, di-, or polyhydric short chain (C_1-6) alcohols; aromatic or aliphatic saturated or unsaturated fatty (C_12-40) alcohols, of cholesterol; and so on. Cholesterol is suitable, or an aromatic or aliphatic saturated or unsaturated fatty alcohol which may have from 6 to 40, preferably from about 10 to 30, more preferably from about 12 to 22 carbon atoms. Examples include oleyl alcohol, cetearyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, and the like. Examples of such ingredients include Oleth 2-100; Steareth 2-100; Beheneth 5-30; Ceteareth 2-100; Ceteth 2-100; Choleth 2-100 wherein the number range means the number of repeating ethylene oxide units, e.g. Ceteth 2-100 means Ceteth where the number of repeating ethylene oxide units ranges from 2 to 100. Derivatives of alkoxylated alcohols are also suitable, such as phosphoric acid esters thereof. Also suitable are alkoxylated alcohols formed with mono-, di-, or polyhydric short chain alcohols, for example those having from about 1 to 6 carbon atoms. Examples include glucose, glycerin, or alkylated derivatives thereof. Examples include glycereth 2-100; gluceth 2-100; methyl gluceth 2-100 and so on. Other types of alkoxylated alcohols are suitable surfactants, including ethylene oxide polymers having varying numbers of repeating EO groups, generally referred to as PEG 12 to 200, for example, PEG-75, which may be purchased from Dow Chemical under the trade name Carbowax PEG-3350.

Other suitable nonionic surfactants include alkoxylated sorbitan and alkoxylated sorbitan derivatives. For example, alkoxylation, in particular ethoxylation of sorbitan provides polyalkoxylated sorbitan derivatives. Esterification of polyalkoxylated sorbitan provides sorbitan esters such as the polysorbates. For example, the polyalkyoxylated sorbitan can be esterified with C_6-30, preferably C_12-22 fatty acids. Examples of such ingredients include Polysorbates 20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate, sorbitan sesquiisostearate, sorbitan stearate, and so on.

Also suitable are various types of silicone or silane-based surfactants. Examples include organosiloxanes substituted with ethylene oxide or propylene oxide groups such as PEG dimethicones which are dimethicones substituted with polyethylene glycols including those having the INCI names PEG-1 dimethicone; PEG-4 dimethicone; PEG-8 dimethicone; PEG-12 dimethicone; PEG-20 dimethicone; and so on. Also suitable are silanes substituted with ethoxy groups or propoxy groups or both, such as various types of PEG methyl ether silanes such as bis-PEG-18 methyl ether dimethyl silane; and so on. Further examples of silicone based surfactants include those having the generic names dimethicone copolyol; cetyl dimethicone copolyol; and so on.

D. Biological Materials

The composition of the present disclosure may contain various types of biological materials such as those derived from cells, fermented materials, and so on. If present, such materials may range from about 0.001%to 30%, preferably from about 0.005%to 25%, more preferably from about 0.01%to 20%by weight of the total composition. Examples include fragments of cellular RNA or DNA, or probiotic microorganisms.

E. Thickeners

Suitable thickeners may be incorporated into the composition of the present disclosure. If present, suggested ranges are from about 0.01%to 30%, preferably from about 0.1%to 20%, more preferably from about 0.5%to 15%by weight of the total composition.

Examples of thickeners include animal, vegetable, mineral, silicone, or synthetic waxes which may have melting points ranging from about 30 to 150℃. Examples of such waxes include waxes made by Fischer-Tropsch synthesis, such as polyethylene or synthetic wax; or various vegetable waxes such as bayberry, candelilla, ozokerite, acacia, beeswax, ceresin, cetyl esters, flower wax, citrus wax, carnauba wax, jojoba wax, japan wax, polyethylene, microcrystalline, rice bran, lanolin wax, mink, montan, bayberry, ouricury, ozokerite, palm kernel wax, paraffin, avocado wax, apple wax, shellac wax, clary wax, spent grain wax, grape wax, and polyalkylene glycol derivatives thereof such as PEG6-20 beeswax, or PEG-12 carnauba wax; or fatty acids or fatty alcohols, including esters thereof, such as hydroxystearic acids (for example 12-hydroxy stearic acid) , tristearin, tribehenin, and so on.

Also suitable as thickening agents are silicas, silicates, silica silylate, and alkali metal or alkaline earth metal derivatives thereof. These silicas and silicates are generally found in the particulate form and include silica, silica silylate, magnesium aluminum silicate, and the like.

Silicone elastomers may also be used as thickening agents. Examples of suitable silicone elastomers for use in the compositions of the present disclosure may be in the powder form, or dispersed or solubilized in solvents such as volatile or non-volatile silicones, or silicone compatible vehicles such as paraffinic hydrocarbons or esters. Examples of silicone elastomer powders include vinyl dimethicone/methicone silesquioxane crosspolymers like Shin-Etsu's KSP-100, KSP-101, KSP-102, KSP-103, KSP-104, KSP-105, hybrid silicone powders that contain a fluoroalkyl group like Shin-Etsu's KSP-200 which is a fluoro-silicone elastomer, and hybrid silicone powders that contain a phenyl group such as Shin-Etsu's KSP-300, which is a phenyl substituted silicone elastomer; and Dow Coming's DC 9506. Examples of silicone elastomer powders dispersed in a silicone compatible vehicle include dimethicone/vinyl dimethicone crosspolymers supplied by a variety of suppliers including Dow Corning Corporation under the tradenames 9040 or 9041, GE Silicones under the tradename SFE 839, or Shin-Etsu Silicones under the tradenames KSG-15, 16, 18. KSG-15 has the CTFA name cyclopentasiloxane/dimethicone/vinyl dimethicone crosspolymer. KSG-18 has the INCI name phenyl trimethicone/dimethicone/phenyl vinyl dimethicone crossoplymer. Silicone elastomers may also be purchased from Grant Industries under the Gransil trademark. Also suitable are silicone elastomers having long chain alkyl substitutions such as lauryl dimethicone/vinyl dimethicone crosspolymers supplied by Shin Etsu under the tradenames KSG-31, KSG-32, KSG-41, KSG-42, KSG-43, and KSG-44. Cross-linked organopolysiloxane elastomers useful in the present disclosure and processes for making them are further described in U.S. Pat. No. 4,970,252 to Sakuta et al., issued Nov. 13, 1990; U.S. Pat. No. 5,760,116 to Kilgour et al., issued Jun. 2, 1998; U.S. Pat. No. 5,654,362 to Schulz, Jr. et al. issued Aug. 5, 1997; and Japanese Patent Application JP 61-18708, assigned to Pola Kasei Kogyo KK, each of which are herein incorporated by reference in its entirety.

Polysaccharides may be suitable aqueous phase thickening agents. Examples of such polysaccharides include naturally derived materials such as agar, agarose, alicaligenes polysaccharides, algin, alginic acid, acacia gum, amylopectin, chitin, dextran, cassia gum, cellulose gum, gelatin, gellan gum, hyaluronic acid, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, pectin, sclerotium gum, xanthan gum, dehydroxanthan gum, pectin, trehelose, gelatin, and so on.

Also suitable are different types of synthetic polymeric thickeners. One type includes acrylic polymeric thickeners comprised of monomers A and B, wherein A is selected from acrylic acid, methacrylic acid, and mixtures thereof; and B is selected from a C1-22 alkyl acrylate, a C1-22 alky methacrylate, and mixtures thereof. Acrylic polymer solutions include those sold by Seppic, Inc., under the tradename or those sold under the tradename Also suitable are acrylates/steareth-20 methacrylate copolymer, which is sold by Rohm &Haas under the tradename Acrysol ICS-1.

Also suitable are acrylate based anionic amphiphilic polymers containing at least one hydrophilic unit and at least one allyl ether unit containing a fatty chain. Anionic amphiphilic polymers of this type are described and prepared in U.S. Patent Nos. 4,677,152 and 4,702,844, both of which are hereby incorporated by reference in their entirety. One commercial example of such polymers are crosslinked terpolymers of methacrylic acid, of ethyl acrylate, of polyethylene glycol (having 10 EO units) ether of stearyl alcohol or steareth-10, in particular those sold by the company Allied Colloids under the names SALCARE SC80 and SALCARE SC90, which are aqueous emulsions containing 30%of a crosslinked terpolymer of methacrylic acid, of ethyl acrylate and of steareth-10 allyl ether (40/50/10) .

Also suitable are acrylate copolymers such as Polyacrylate-3 which is a copolymer of methacrylic acid, methylmethacrylate, methylstyrene isopropylisocyanate, and PEG-40 behenate monomers; Polyacrylate-10 which is a copolymer of sodium acryloyldimethyltaurate, sodium acrylate, acrylamide and vinyl pyrrolidone monomers; or Polyacrylate-11, which is a copolymer of sodium acryloyldimethyl taurate, sodium acrylate, hydroxyethyl acrylate, lauryl acrylate, butyl acrylate, and acrylamide monomers.

Also suitable are crosslinked acrylate based polymers where one or more of the acrylic groups may have substituted long chain alkyl (such as 6-40, 10-30, and the like) groups, for example acrylates/C10-30 alkyl acrylate crosspolymer which is a copolymer of C10-30 alkyl acrylate and one or more monomers of acrylic acid, methacrylic acid, or one of their simple esters crosslinked with the allyl ether of sucrose or the allyl ether of pentaerythritol. Such polymers are commonly sold under the Carbopol or Pemulen tradenames and have the CTFA name carbomer.

One suitable type of aqueous phase thickening agent are acrylate based polymeric thickeners sold by Clariant under the Aristoflex trademark such as Aristoflex AVC, which is ammonium acryloyldimethyltaurate/VP copolymer; Aristoflex AVL which is the same polymer has found in AVC dispersed in mixture containing caprylic/capric triglyceride, trilaureth-4, and polyglyceryl-2 sesquiisostearate; or Aristoflex HMB which is ammonium acryloyldimethyltaurate/beheneth-25 methacrylate crosspolymer, and the like.

Also suitable as thickening agents are various polyethylene glycols (PEG) derivatives where the degree of polymerization ranges from 1,000 to 200,000. Such ingredients are indicated by the designation "PEG" followed by the degree of polymerization in thousands, such as PEG-45M, which means PEG having 45,000 repeating ethylene oxide units. Examples of suitable PEG derivatives include PEG 2M, 5M, 7M, 9M, 14M, 20M, 23M, 25M, 45M, 65M, 90M, 115M, 160M, 180M, and the like.

Also suitable are polyglycerins which are repeating glycerin moieties where the number of repeating moieties ranges from 15 to 200, preferably from about 20-100. Examples of suitable polyglycerins include those having the CTFA names polyglycerin-20, polyglycerin-40, and the like.

F. Oils

In the case that the compositions of the present disclosure are in solution, suspension, anhydrous, or especially emulsion form, the composition may contain an oil ingredient. Oily ingredients are desirable for the skin moisturizing and protective properties. Suitable oils include silicone oils, esters, vegetable oils, synthetic oils, including but not limited to those set forth herein.

The oils may be volatile or nonvolatile, and are preferably in the form of a pourable liquid at room temperature. Suitable volatile oils generally have a viscosity ranging from about 0.5 to 5 centistokes 25℃ and include linear silicones, cyclic silicones, paraffinic hydrocarbons, or mixtures thereof. Cyclic and linear volatile silicones are available from various commercial sources including Dow Corning Corporation and General Electric. The Dow Corning linear volatile silicones are sold under the tradenames Dow Corning 244, 245, 344, and 200 fluids. These fluids include hexamethyldisiloxane (viscosity 0.65 centistokes (abbreviated cst) ) , octamethyltrisiloxane (1.0 cst) , decamethyltetrasiloxane (1.5 cst) , dodecamethylpentasiloxane (2 cst) and mixtures thereof, with all viscosity measurements being at 25℃. Suitable branched volatile silicones include alkyl trimethicones such as methyl trimethicone. Methyl trimethicone may be purchased from Shin-Etsu Silicones under the tradename TMF-1.5, having a viscosity of 1.5 centistokes at 25℃. Also suitable as the volatile oils are various straight or branched chain paraffinic hydrocarbons having 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, more preferably 8 to 16 carbon atoms. Suitable hydrocarbons include pentane, hexane, heptane, decane, dodecane, tetradecane, tridecane, and C_8-20 isoparaffins as disclosed in U.S. Pat. Nos. 3,439,088 and 3,818,105, both of which are hereby incorporated by reference.

A variety of nonvolatile oils are also suitable for use in the compositions of the present disclosure. The nonvolatile oils generally have a viscosity of greater than about 5 to 10 centistokes at 25℃, and may range in viscosity up to about 1,000,000 centipoise at 25℃. Examples of nonvolatile oils include, but are not limited to esters, hydrocarbon oils, glyceryl esters of fatty acids, and nonvolatile silicones.

Suitable esters are mono-, di-, and triesters. Examples of monoester oils that may be used in the compositions of the present disclosure include hexyl laurate, butyl isostearate, hexadecyl isostearate, cetyl palmitate, isostearyl neopentanoate, stearyl heptanoate, isostearyl isononanoate, steary lactate, stearyl octanoate, stearyl stearate, isononyl isononanoate, and so on. Examples of diester oils that may be used in the compositions of the present disclosure include diisotearyl malate, neopentyl glycol dioctanoate, dibutyl sebacate, dicetearyl dimer dilinoleate, dicetyl adipate, diisocetyl adipate, diisononyl adipate, diisostearyl dimer dilinoleate, diisostearyl fumarate, diisostearyl malate, dioctyl malate, and so on. Examples of triesters include esters of arachidonic, citric, or behenic acids, such as triarachidin, tributyl citrate, triisostearyl citrate, tri C_12-13 alkyl citrate, tricaprylin, tricaprylyl citrate, tridecyl behenate, trioctyldodecyl citrate, tridecyl behenate, or tridecyl cocoate, tridecyl isononanoate, and so on. Esters suitable for use in the composition of the present disclosure are further described in the C. T. F. A. Cosmetic Ingredient Dictionary and Handbook, Eleventh Edition, 2006, under the classification of "Esters" , the text of which is hereby incorporated by reference in its entirety.

Suitable nonvolatile hydrocarbon oils include paraffinic hydrocarbons and olefins, preferably those having greater than about 20 carbon atoms. Examples of such hydrocarbon oils include C_24-28 olefins, C_30-45 olefins, C_20-40 isoparaffins, hydrogenated polyisobutene, polyisobutene, polydecene, hydrogenated polydecene, mineral oil, pentahydrosqualene, squalene, squalane, and mixtures thereof. In one preferred embodiment such hydrocarbons have a molecular weight ranging from about 300 to 1000 Daltons.

Synthetic or naturally occurring glyceryl esters of fatty acids, or triglycerides, are also suitable for use in the compositions. Both vegetable and animal sources may be used. Examples of such oils include castor oil, lanolin oil, C_10-18 triglycerides, caprylic/capric/triglycerides, sweet almond oil, apricot kernel oil, sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, ink oil, olive oil, palm oil, illipe butter, rapeseed oil, soybean oil, grapeseed oil, sunflower seed oil, walnut oil, and the like. Also suitable are synthetic or semi-synthetic glyceryl esters, such as glyceryl stearate, diglyceryl diiosostearate, polyglyceryl-3 isostearate, polyglyceryl-4 isostearate, polyglyceryl-6 ricinoleate, glyceryl dioleate, glyceryl diisotearate, glyceryl tetraisostearate, glyceryl trioctanoate, diglyceryl distearate, glyceryl linoleate, glyceryl myristate, glyceryl isostearate, PEG castor oils, PEG glyceryl oleates, PEG glyceryl stearates, PEG glyceryl tallowates, and so on.

Nonvolatile silicone oils, both water soluble and water insoluble, are also suitable for use in the composition. Examples of such silicone oils include dimethicone, amodimethicone, phenyl dimethicone, diphenyl dimethicone, phenyl trimethicone, trimethylsiloxyphenyl dimethicone, or alkyl dimethicones such as cetyl dimethicone. Phenyl trimethicone can be purchased from Dow Corning Corporation under the tradename 556 Fluid. Trimethylsiloxyphenyl dimethicone can be purchased from Wacker-Chemie under the tradename PDM-1000. Cetyl dimethicone, also referred to as a liquid silicone wax, may be purchased from Dow Corning as Fluid 2502, or from DeGussa Care &Surface Specialties under the trade names Abil Wax 9801, or 9814.

G. Sunscreens

It may also be desirable to include one or more sunscreens in the compositions of the present disclosure. Such sunscreens include chemical UVA or UVB sunscreens or physical sunscreens in the particulate form. Inclusion of sunscreens in the compositions containing the whitening active ingredient will provide additional protection to skin during daylight hrs and promote the effectiveness of the whitening active ingredient on the skin. If present, the sunscreens may range from about 0.1%to 50%, preferably from about 0.5%to 40%, more preferably from about 1%to 35%by weight of the total composition.

Examples of suitable UVA sunscreen compounds include 4-methyldibenzoylmethane, 2-methyldibenzoylmethane, 4-isopropyldibenzoylmethane, 4-tert-butyldibenzoylmethane, 2, 4-dimethyldibenzoylmethane, 2, 5-dimethyldibenzoylmethane, 4, 4'diisopropylbenzoylmethane, 4-tert-butyl-4'-methoxydibenzoylmethane, 4, 4'-diisopropylbenzoylmethane, 2-methyl-5-isopropyl-4'-methoxydibenzoymethane, 2-methyl-5-tert-butyl-4'-methoxydibenzoylmethane, and so on. Particularly preferred is 4-tert-butyl-4'-methoxydibenzoylmethane, also referred to as Avobenzone. Avobenzone is commercially available from Givaudan-Roure under the trademark 1789, and Merck &Co. under the tradename 9020. Other types of UVA sunscreens include dicamphor sulfonic acid derivatives, such as ecamsule, a sunscreen sold under the trade name which is terephthalylidene dicamphor sulfonic acid.

The composition may contain from about 0.001-20%, preferably 0.005-5%, more preferably about 0.005-3%by weight of the composition of UVA sunscreen.

Examples of suitable UVB sunscreen compounds include alpha-cyano-beta, beta-diphenyl acrylic acid esters as set forth in U.S. Pat. No. 3,215,724, which is hereby incorporated by reference in its entirety. One particular example of an alpha-cyano-beta, beta-diphenyl acrylic acid ester is Octocrylene, which is 2-ethylhexyl 2-cyano-3, 3-diphenylacrylate. If present, suitable amounts range from about 0.001-10%by weight. Octocrylene may be purchased from BASF under the tradename N-539.

Other suitable UVB sunscreens include benzylidene camphor derivatives as set forth in U.S. Pat. No. 3,781,417, which is hereby incorporated by reference in its entirety, such as 4-methylbenzylidene camphor, which is a lipid soluble UVB sunscreen compound sold under the tradename Eusolex 6300 by Merck. Also suitable are cinnamate derivatives, such as ethylhexyl methoxycinnamate, also referred to as Octoxinate or octyl methoxycinnamate. The compound may be purchased from Givaudan Corporation under the tradename MCX, or BASF under the tradename MC 80.

Also suitable as UVB sunscreens are mono-, di-, and triethanolamine derivatives of such methoxy cinnamates including diethanolamine methoxycinnamate. Cinoxate, the aromatic ether derivative of the above compound is also acceptable. If present, the Cinoxate should be found at no more than about 3%by weight of the total composition.

Also suitable as UVB sunscreens are various benzophenone derivatives, such as Benzophenone 3 (also referred to as Oxybenzone) , Benzophenone 4 (also referred to as Sulisobenzone) , Benzophenone 5 (Sulisobenzone Sodium) , and the like.

Also suitable as UVB sunscreens are certain menthyl salicylate derivatives, such as homomenthyl salicylate (also known as Homosalate) or menthyl anthranilate. Homosalate is available commercially from Merck under the trademark HMS and menthyl anthranilate is commercially available from Haarmann &Reimer under the trademark If present, the Homosalate should be found at no more than about 15%by weight of the total composition.

Also suitable as UVB sunscreens are various amino benzoic acid derivatives, such as PABA, ethyl hexyl dimethyl PABA (Padimate O) , ethyldihydroxypropyl PABA, and the like. If present, Padimate O should be found at no more than about 8%by weight of the total composition.

Salicylate derivatives are also acceptable UVB sunscreens. Such compounds include octyl salicylate, TEA-salicylate, DEA-salicylate, and mixtures thereof.

If present, the amount of the UVB chemical sunscreen present may range from about 0.001-45%, preferably 0.005-40%, more preferably about 0.01-35%by weight of the total composition.

If desired, the compositions of the present disclosure may be formulated to have certain SPF (sun protective factor) values ranging from about 1-50, preferably about 2-45, most preferably about 5-30. Calculation of SPF values is well known in the art.

H. Vitamins

It may be desirable to incorporate one or more vitamins in the composition of the present disclosure. If present, suggested ranges are from about 0.001%to 20%, preferably from about 0.005%to 15%, more preferably from about 0.010%to 10%by weight of the total composition. Preferably, such vitamins and/or vitamin derivatives are operable to scavenge free radicals in the form of singlet oxygen. Such vitamins may include tocopherol or its derivatives such as tocopherol acetate, tocopherol ferulate, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18, tocophereth-50, tocophersolan, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate dioleyl tocopheryl methylsilanol; ascorbic acid or its derivatives such as ascorbyl palmitate, magnesium ascorbyl phosphate; Vitamin A or its derivatives such as retinyl palmitate; or vitamins D, K, B, or derivatives thereof.

I. Antioxidants

Non-limiting examples of antioxidants that can be used in the compositions of the present disclosure include acetyl cysteine, ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butyl hydroquinone, cysteine, cysteine HCl, diamylhydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, disodium ascorbyl sulfate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters of ascorbic acid, ethyl ferulate, ferulic acid, gallic acid esters, hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbate, natural botanical anti-oxidants such as green tea or grape seed extracts, nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid, potassium sulfite, propyl gallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycolate, sorbityl furfural, thiodiglycol, thiodiglycolamide, thiodiglycolic acid, thioglycolic acid, thiolactic acid, thiosalicylic acid, and tris (nonylphenyl) phosphite.

J. Preservatives

Non-limiting examples of preservatives that can be used in the compositions of the present disclosure include quaternary ammonium preservatives such as polyquaternium-1 and benzalkonium halides (e.g., benzalkonium chloride ( “BAC” ) and benzalkonium bromide) , parabens (e.g., methylparabens and propylparabens) , phenoxy ethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal or combinations thereof.

K. Pigments or Nanopigments

Pigments are intended to confer a certain colour on the compositions before and/or after their application to the skin, lips and/or superficial body growths. It may be desirable to incorporate one or more pigments in the composition of the present disclosure. If present, suggested ranges are from about 0.01%to 50%, preferably from about 1%to 25%, more preferably from about 2%to 15%by weight of the total composition. Examples of suitable pigments for use in the compositions of the present disclosure may be in the form of powders, particles, or microspheres, or dispersed or solubilized in solvents. These pigments can be lakes, inorganic or organic pigments and/or pearlescent pigments or alternatively colorants. Preferred inorganic pigments are, for example, titanium, zirconium or cerium oxides, as well as zinc, iron or chromium oxides and ferric blue. Preferred organic pigments are, for example, carbon black and barium, strontium, calcium and aluminium lakes. Preferred pearlescent agents are, for example, mica covered with titanium oxide, with iron oxide, with natural pigment or with bismuth oxychloride, such as coloured titanium oxide-coated mica.

By "nanopigments" are intended pigments in which the average size of the elementary particles ranges from 5 to 100 nm. Preferably, the average size of the elementary particles of the nanopigments of the present disclosure ranges from 10 to 50 nm.

L. Sequestering agents

Non-limiting examples of sequestering agents that can be used in the compositions of the present disclosure include ethylene diamino tetraacetate salts (EDTA) , in particular disodium and tetrasodium ethylene diamino tetraacetate salts, and the acid form thereof; diethylene triamino pentaacetate salts (DTPA) and the acid form thereof; propylene diaminotetraacetate salts (PDTA) and the acid form thereof; hydroxyethylethylene diaminotriacetate salts (HEDTA) and the acid form thereof; tetrahydroxypropyl ethylenediamine; pentetate salts such as pentasodium pentetate and the acid form thereof; etidronate salts such as tetrasodium etidronate, and the acid form thereof; nitrilotriacetate (NTA) salts and the acid form thereof; acrylic acid/acrylamidomethyl propane sulfonic acid copolymer polyacrylate salts, and the acid form thereof; phosphonate salts and the acid form thereof; poly-or metaphosphate salts and the acid form thereof; citrate salts and citric acid, galactaric acid and galactaric acid salts; iminodisuccinate salts and the acid form thereof; zeolithe; bentonite; laminar disilicate salts and the acid form thereof; N-acylethylenediaminotriacetate salts and the acid form thereof; phytic acid and phytic acid salts.

Other suitable ingredients that can be used in the compositions of the present disclosure include caprylyl glycol/phenoxyethanol/hexylene glycol, dicaprylyl carbonate, isopropyl isostearate, phenoxyethanol/caprylyl glycol, dextrin palmitate, magnesium sulfate, and the like.

Those skilled in the art can select the amount of these ingredients based on the final use of the cosmetic composition. As those skilled in the art will appreciate, the compositions according to the present disclosure may comprise a total of about 20%to 98%, preferably about 30%to 90%, and more preferably about 40%to 80%by weight of the composition of one or more additional cosmetically acceptable ingredient.

The cosmetic compositions of the present disclosure can be in the form of a liquid, a lotion, a thickened lotion, a gel, a cream, a milk, an ointment, a paste, a powder, a make-up, or a solid tube stick and can be optionally be packaged as an aerosol and can be provided in the form of a mousse such as an aerosol mousse, a foam or a spray foams, sprays, sticks, a gel, a plaster, a powder, a cleanser, a soap or aerosols or wipes.

Preferably, the cosmetic compositions of the present disclosure are topical compositions in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of O/W or W/O type, O/W/O or W/O/W-type) , PET-emulsions, multiple emulsions, bickering emulsions, hydrogels, alcoholic gels, lipogels, one or multiphase solutions or a vesicular dispersion and other usual compositions, which can also be applied by pens, as masks or as sprays. The emulsions can also contain anionic, nonionic, cationic or amphoteric surfactant (s) . Preferred compositions according to the present disclosure are skin care preparations, hair-care preparations, or functional preparations.

The amount of the cosmetic composition according to the present disclosure, which is to be applied to the skin depends on the concentration of the active ingredients in the compositions and the desired cosmetic or pharmaceutical effect. For example, application can be such that a cream is applied to the skin. A cream is usually applied in an amount of 2 mg cream/cm² skin. The amount of the composition which is applied to the skin is, however, not critical, and if with a certain amount of applied composition the desired effect cannot be achieved, a higher concentration of the active ingredients can be used e.g. by applying more of the composition or by applying compositions which contain more active ingredient. The cosmetic composition according to the present disclosure is preferably applied at least once per day, e.g. twice or three times a day.

Regarding the kind of the cosmetic compositions and the preparation of the cosmetic compositions as well as for further suitable additives, it can be referred to the pertinent literature, e.g. to Novak G.A., Die kosmetischen 2, Die kosmetischen Rohstoffe, wissenschaftliche Grundlagen (Verlag für Chem. Industrie H. Ziolkowski KG, Augsburg) .

Method and Use

According to the second aspect, the present disclosure is concerned with a method for manufacturing a cosmetic composition comprising at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate, comprising:

a. adding the at least one Laminaria extract and the at least one salt of hydrolyzed hyaluronate into an aqueous solvent to form a water phase;

Preferably, the aqueous solvent may comprise water, and preferably comprise at least 50%, or at least 75%, or at least 90%, or at least 97%, or at least 99%by weight of water, relative to the total weight of the aqueous solvent. Optionally, the aqueous solvent, besides water, may comprise one or more water-miscible solvent selected from monols, such as ethanol, in particular denatured ethanol, diols, such as ethylene glycol, propylene glycol (e.g. 1, 3-propylene glycol) , and butylene glycol (e.g. 1, 3-butylene glycol) , and mixtures thereof. The aqueous solvent may comprise less than 50%, or less than 25%, or less than 10%, or less than 3%, or less than 1%by weight of water-miscible solvent, relative to the total weight of the aqueous solvent.

According to the third aspect, the present disclosure is concerned with a method for seborrhea control, inhibiting lipogenesis process, reducing sebum production of skin, inhibiting lipogenesis in sebocytes of skin, improving lipid level in sebocytes of skin, treating hyperseborrhea, and/or treating acne (or acne prone) skin, comprising topically applying a cosmetic composition comprising at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate to skin in need thereof.

According to the fourth aspect, the present disclosure is concerned with use of a cosmetic composition comprising at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate for seborrhea control, inhibiting lipogenesis process, reducing sebum production of skin, inhibiting lipogenesis in sebocytes of skin, improving lipid level in sebocytes of skin, treating hyperseborrhea, and/or treating acne (or acne prone) skin.

The invention will be further described in connection with the following example which is set forth for purposes of illustration without being limiting in nature.

EXAMPLES

The following examples are given by way of illustration of the present invention and shall not be interpreted as limiting the scope.

Main raw materials used, trade names and suppliers thereof were listed in Table 1.

Table 1. Raw Materials

Sample preparation

Preparation of Zinc Hydrolyzed Hyaluronate (miniHA-Zn) samples

1 g miniHA-Zn powder (Hybloom^TM Zinc Hyaluronate (HA-Zn) , Bloomage, molecular weight: ≤1.00 M Da, purity: ≥91%) was added into 9 mL purified water and placed on an oscillator for 30 minutes until complete dissolution to form a stock solution with a concentration of 10%, and the stock solution was stored at 4℃. Then, it was diluted with cell culture complete medium to 0.001%, 0.002%, 0.004%, or 0.008%on the treatment day.

Preparation of Laminaria Saccharina extract (LS extract) samples

1 g Phlorogine (Seppic, containing 1.9%dry LS extract and balance of inert carriers) was dissolved in 9 mL purified water with vortex for complete dissolution to form a stock solution with a concentration of 10%, and the stock solution was filtrated and stored at 4℃. Then, it was diluted with cell culture complete medium to 0.125%, 0.25%, 0.5%, or 1%(corresponding to 0.002375%, 0.00475%, 0.0095%, or 0.019%of LS extract) on the treatment day.

Test method of seborrhea control efficacy

1. Cell culture

Human immortalized SZ95 sebocytes, originated from human facial sebaceous glands (Zouboulis et al. 1999) , were cultured in Basal Medium (Sigma-Aldrich) supplemented with 10%fetal bovine serum (Corning) , 1 mM CaCl₂, 5 ng/ml human recombinant epidermal growth factor (Pufei, China) , 1%Antibiotic-Antimycotic (Gibco^TM, Thermo Fisher Scientific) at 37℃ in a 5%CO₂ humidified incubator. The medium was changed every other day, and cells were sub-cultured at 60-80%confluence.

2. Cell treatment

The cells were then detached with TrypLE^TM Express (Gibco) and transferred to 96-well black-well/clear-bottom plates (PE View plate) at a density of 10,000 cells/well. The cells were maintained in supplemented human sebocyte growth medium (Sigma, FB205) overnight at 37℃ and 5%CO₂. Then the cells were treated with miniHA-Zn sample (0.001%, 0.002%, 0.004%, 0.008%in supplemented human sebocyte growth medium) , LS extract sample (0.002375%, 0.00475%, 0.0095%, 0.019%in supplemented human sebocyte growth medium) or the combination of these two for 72 h.

3. Lipogenesis inhibition rate (%)

After incubation, the cells were washed twice with DPBS buffer, all cells were fixed in 4%paraformaldehyde for 5 min, then 100 μl of a 1 μg/ml Nile red (Sigma-Aldrich) solution in phosphate-buffered saline was added to each well and incubated at 37℃ for 20 min. Fluorescence was measured on an Operetta CLS high content imaging system (PE) . Results were expressed as the relative fluorescence units per cell using 485 nm excitation and 565 nm emission wavelengths for neutral lipids and 540 nm excitation and 620 nm emission wavelength for polar lipids (Alestas et al., 2005) . Nuclear DNA was labelled with DAPI (Invitrogen) . The relative lipogenesis value was calculated using the following equation:

Relative lipogenesis value %= (Mean Flurorescent Intensity value _active /Mean Flurorescent Intensity value _control) × 100%

Lipogenesis inhibition rate = 1 -Relative lipogenesis value %

The experimental results were evaluated by the isobole method for synergistic effects, as described in the article titled "Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective" Medicina (Kaunas) . 2019; 55(4) : 110, which is herein incorporated in its entirety. According to the isobole method, OE means the observed effects, and da and db represent the doses or concentrations of active a and active b, respectively. Thus, OE (da, db) means the observed effects of the combination of actives a at da and b at db; and OE (da) means the observed effects of active a at da and OE (db) means the observed effects of active b at db, and three mathematic equations may be derived:

OE (da, db) = OE (da) +OE (db) (Equation 1)

OE (da, db) > OE (da) +OE (db) (Equation 2)

OE (da, db) < OE (da) +OE (db) (Equation 3)

If the observed effects satisfy equation (1) , the effects of two actives are the simple sum of the single effects, and two actives do not interact and thus there is no synergy.

If the observed effects satisfy equation (2) , the result represents the real synergism (or potentiation) , where the effects of two actives are more than the simple sum of the single effects.

If the observed effects satisfy equation (3) , the result represents the opposite effects of synergism, as the effects of two actives are less than the simple sum of the single effects.

The results of seborrhea control efficacy were illustrated in Figures 1-2 and Tables 2 -3, which showed that the active a (LS extract) and the active b (miniHA-Zn) with different concentrations used in combination at different ratio exhibited synergistic effects in terms of the lipogenesis inhibition. Results shown in the same Table represent experiments carried out on the same day with the same batch of cells. The synergistic effects between LS extract and miniHA-Zn made it possible to achieve superior seborrhea control efficacy at lower concentrations of actives.

Table 2. Seborrhea control efficacy of Examples 1-5

Table 3. Seborrhea control efficacy of Examples 6-13

*Note: Lipogenesis inhibition rate data different from that of Example 2 in Table 2 due to different cell batches

Formulations

Examples 14-27 were prepared according to the formulations as shown in Tables 4-5.

Table 4. Formulation of Examples 14-20

Table 5. Formulation of Examples 21-26

Although the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the disclosure as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

References:

Cemil B.C., et al. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients. Postepy Dermatol Alergol. 2016; 33 (4) : 294-299.

Im, M., et al. Epigallocatechin-3-gallate suppresses IGF-I-induced lipogenesis and cytokine expression in SZ95 sebocytes. J Invest Dermatol. 2012; 132 (12) : 2700-2708.

Alestas, T., et al. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. Journal of Molecular Medicine. 2005; 84 (1) : 75-87.

Pezzani R, et al. Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective, Medicina (Kaunas) . 2019; 55 (4) : 110

Claims

A cosmetic composition comprising at least one Laminaria extract and at least one salt of hydrolyzed hyaluronate.
The cosmetic composition according to claim 1, wherein the Laminaria extract is selected from Laminaria Saccharina extract, Laminaria Digitata extract, Laminaria Ochroleuca extract, Laminaria Algae extract, and mixtures thereof; preferably, the Laminaria extract is Laminaria Saccharina extract.
The cosmetic composition according to claim 1 or 2, wherein the salt of hydrolyzed hyaluronate is selected from Hydrolyzed Zinc Hyaluronate, Hydrolyzed Potassium Hyaluronate, Hydrolyzed Calcium Hyaluronate, and mixtures thereof; preferably, the salt of hydrolyzed hyaluronate is Hydrolyzed Zinc Hyaluronate.
The cosmetic composition according to any one of claims 1-3, wherein the salt of hydrolyzed hyaluronate has a molecular weight of no more than 1 MDa, preferably from 5 kDa to 500 kDa, more preferably from 100 kDa to 300 kDa.
The cosmetic composition according to any one of claims 1-4, wherein the cosmetic composition has a weight ratio between the Laminaria extract and the salt of hydrolyzed hyaluronate equal to or above 1: 100, preferably from about 1: 10 to about 500: 1, more preferably from about 1: 2 to about 100: 1, particularly preferably from about 1: 1 to about 40: 1.
The cosmetic composition according to any one of claims 1-5, wherein based on the total weight of the cosmetic composition, the Laminaria extract is present in the cosmetic composition in an amount of from about 0.0005%to about 5%by weight, preferably from about 0.0008%to about 1%by weight, more preferably from about 0.001%to about 0.1%by weight (on dry weight basis) .
The cosmetic composition according to any one of claims 1-6, wherein based on the total weight of the cosmetic composition, the salt of hydrolyzed hyaluronate is present in the cosmetic composition in an amount of from about 0.0001%to about 5%by weight, preferably from about 0.0002%to about 1%by weight, more preferably from about 0.001%to about 0.05%by weight.
The cosmetic composition according to any one of claims 1-7, wherein based on the total weight of the cosmetic composition, the cosmetic composition comprises from about 0.001%to about 0.1%by weight (on dry weight basis) of Laminaria Saccharina extract and from about 0.001%to about 0.05%by weight of Hydrolyzed Zinc Hyaluronate, and wherein the weight ratio between Laminaria Saccharina extract and Hydrolyzed Zinc Hyaluronate is in a range of from about 1: 1 to about 40: 1.
The cosmetic composition according to any one of claims 1-8, wherein the cosmetic composition further comprises at least one of active ingredients selected from sugar derivatives, natural extracts, ferments, vitamins, urea, caffeine, salicylic acid and its derivatives, alpha-hydorxy acids and their derivatives, retinoids, niacinamide, humectants, sunscreens, essential oils of mint, aloe vera or ginseng, and mixtures thereof.
A method for manufacturing the cosmetic composition according to any one of claims 1-9, comprising:

a. adding the at least one Laminaria extract and the at least one salt of hydrolyzed hyaluronate into an aqueous solvent to form a water phase;

b. homogenizing the water phase at room temperature to form a clear solution; and

c. continuing to homogenize the solution for 10-30 mins to obtain the cosmetic composition.
A cosmetic product for seborrhea control comprising the cosmetic composition according to any one of claims 1-9.
Non-therapeutic use of the cosmetic composition according to any one of claims 1-9 for seborrhea control.
A non-therapeutic method for seborrhea control, comprising topically applying the cosmetic composition according to any one of claims 1-9 or the cosmetic product according to claim 11 to skin in need thereof.