WO2014041542A2

WO2014041542A2 - Topical compositions for the treatment of acne

Info

Publication number: WO2014041542A2
Application number: PCT/IL2013/050772
Authority: WO
Inventors: Sharon ROZENBLAT
Original assignee: Kamedis Ltd
Priority date: 2012-09-13
Filing date: 2013-09-12
Publication date: 2014-03-20
Also published as: WO2014041542A3; TW201417822A

Abstract

The invention is directed to topical formulations comprising plant extracts together with additional ingredients. The invention is further directed to use of the formulations in treating acne. In particular, the invention is directed to a topical formulation comprising Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid.

Description

TOPICAL COMPOSITIONS FOR THE TREATMENT OF ACNE

FIELD OF THE INVENTION

[0001] The invention is directed to topical formulations comprising plant extracts together with additional ingredients. The invention is further directed to use of the formulations in treating acne.

BACKGROUND OF THE INVENTION

[0002] Acne vulgaris (cystic acne or "acne") is a common human skin disease, characterized by areas of skin with redness, comedones (blackheads and whiteheads), papules (pinheads), pustules (pimples), nodules (large papules) and possibly scarring. Acne affects mostly skin with the densest population of sebaceous follicles; these areas include the face, the upper part of the chest, and the back. Severe acne is inflammatory, but acne can also manifest in noninflammatory forms. The lesions are caused by changes in pilosebaceous units, skin structures consisting of a hair follicle and its associated sebaceous gland, changes that require androgen stimulation. Acne occurs most commonly during adolescence, and often continues into adulthood. Acne is considered to be one of the most widespread skin diseases in the Western population. The prevalence of acne is about 25% among adults and 90% among teenagers suffering from acne outbreaks between the ages 12 to 24. The condition is characterized by bumps usually appearing on the face, neck, back, chest and shoulders. The severity of acne varies greatly among individuals and genetic background plays an important role. Pathogenic factors include androgen-induced sebum secretion, follicular hyperkeratosis, microbial population, and immunological and inflammatory processes.

[0003] According to the widespread theory, the initial event in the development of an acne lesion is abnormal desquamation of the keratinocytes preventing normal sebum drain. An increase in circulating androgens in teenagers stimulates the sebum production causing the surrounding hair follicle to swell. These events combine to create an environment within the sebaceous glands that is favorable for the colonization of the bacteria, Propionibacterium acnes. Propagating P. acnes secrete various inflammatory molecules and chemotactic factors that initiate the local inflammatory response and possibly induce keratinocyte hyperproliferation as well. However, evidence has emerged showing that inflammatory events can precede the lesion formation and that the development of plugs is influenced, to some degree, by inflammation caused by P acnes.

[0004] Lesional types characteristic for active acne may be divided inflammatory and non-inflammatory lesions. [0005] Non-inflammatory lesions are known also as comedones. Noninflammatory lesions are solid small pale papules, typically with a diameter of less than 1 mm, containing a core of white debris comprised of sebum and keratotic debris (closed comedones) or a dark-gray core of debris due to exposure to air and subsequent oxidation (open comedones).

[0006] Inflammatory lesions include papules, pustules, and nodules. Inflammatory lesions range from elevated solid erythematous papules, pustules containing a core of purulent material, to larger indurated lesions. The latter are designated as nodules if they are at least 5 mm in diameter.

[0007] In light of the disadvantages of known treatments for acne, there is a need for a topical composition comprising herbs for the treatment thereof.

SUMMARY OF THE INVENTION

[0008] Embodiments of the invention are directed to a topical formulation comprising Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid. Further embodiments are directed to the above formulation for use in treating or preventing acne. According to some embodiments, the formulation further comprises one or more of dipotassium glycyrrhizate, Chamomilla recutita (matricaria) flower extract and Hamamelis virginiana (witch hazel).

[0009] According to some embodiments, the formulation further comprises one or more of salicylic acid, allantoin and obisabolol. According to some embodiments, the formulation further comprises one or more of kaolin, zinc oxide, hippophae rhamnoides oil, usnic acid, hydroxyphenyl propamidobenzoic acid, titanium dioxide. According to some embodiments, the formulation further comprises one or more of imidazolidinyl urea, methylchloroisothiazolinone and methylisothiazolinone.

[00010] Some embodiments of the invention are directed to a topical formulation comprising Portulaca oleracea extract, Sapindus mukorossi fruit extract and at least one of ammonium laureth sulfate, cocamidopropyl betaine, cocamide MEA, cocamide DEA. According to some embodiments, the above formulation is used in treating or preventing acne.

[0001 1 ] According to some embodiments, the formulation provides a synergistic effect regarding sebum secretion reduction, absorbance of skin oils, anti-inflammatory activity, anti-bacterial activity, wound healing properties, anti-oxidative activity, skin irritation reduction, skin absorbance of the formulation, or any combination thereof. [00012] Further embodiments of the invention are directed to methods of treating acne comprising topically applying a topical formulation as detailed herein to a subject in need thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[00013] The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

[00014] Figures 1A, 1 B, 1 C and 1 D present graphs showing comparative results, comparing the effect of a treatment with a face cream according to exemplary embodiments of the invention to a previous, less effective, formulation on individuals afflicted with acne. Particularly, Figures 1A and 1 B present results of a face cream according to an embodiment of the invention and Figures 1 C and 1 D present results of a previous, less effective, formulation.

[00015] Figures 2A, 2B, 2C and 2D present graphs showing comparative results, comparing the effect of a treatment with a spot treatment formulation according to exemplary embodiments of the invention to a previous, less effective, formulation on individuals afflicted with acne. Figures 2A and 2B present results of a spot treatment according to an embodiment of the invention and Figures 2C and 2D present results of a previous, less effective, spot treatment formulation.

[00016] Figure 3 presents a graph showing the reduction in acne inflammatory lesions of patients treated with salicylic acid alone and with salicylic acid combined with an herbal mixture.

DESCRIPTION OF THE DETILAED EMBODIMENTS OF THE INVENTION

[00017] One embodiment of the invention is a topical formulation comprising Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum Indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid. Some embodiments of the invention are directed to a topical formulation comprising Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid for use in treating and/or preventing acne.

[00018] According to some embodiments, the topical formulation further comprises one or more of the following agents: zinc oxide, kaolin, titanium dioxide, hippophae rhamnoides oil, hydroxyphenyl propamidobenzoic acid, usnic acid, dipotassium glycyrrhizate, Chamomilla recutita (matricaria) flower extract, salicylic acid, glycerin, Hamamelis virginiana (witch hazel) water, allantoin, obisabolol or any combination thereof.

[00019] According to some embodiments, the topical formulation further comprises one or more of zinc oxide, kaolin, titanium dioxide, hippophae rhamnoides oil, hydroxyphenyl propamidobenzoic acid and usnic acid or any combination thereof.

[00020] According to some embodiments the topical formulation further comprises one or more of dipotassium glycyrrhizate, Chamomilla recutita (matricaria) flower extract, salicylic acid, glycerin, Hamamelis virginiana (witch hazel) water, allantoin and o bisabolol or any combination thereof.

[00021 ] According to some embodiments the topical formulation comprises Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum Indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid and one or more of salicylic acid, allantoin, obisabolol, dipotassium glycyrrhizate, Chamomilla recutita (matricaria) flower extract and Hamamelis virginiana (witch hazel). According to some embodiments, the topical formulation is paraben free. According to some embodiments, the pH of the formulation is between about 3.5-4.5. According to some embodiments, the pH of the formulation is between about 3.0-5.0. According to some embodiments, the pH of the formulation is between about 3.0-5.5. In some embodiments the formulation is in a form of a face cream.

[00022] According to some embodiments the topical formulation Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum Indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid. According to some embodiments, the formulation further comprises one or more of kaolin, zinc oxide, titanium dioxide, Hippophae rhamnoides oil and hydroxyphenyl propamidobenzoic Acid. According to further embodiments, the formulation further comprises one or more of imidazolidinyl urea, methylchloroisothiazolinone and methylisothiazolinone. According to some embodiments, the topical formulation is paraben free. According to some embodiments, the pH of the formulation is between about 7.0-8.0. In some embodiments, the formulation is in a form of a spot treatment formulation.

[00023] Some embodiments of the invention are directed to a topical formulation comprising Portulaca oleracea extract, Sapindus mukorossi fruit extract, at least one of ammonium laureth sulfate, cocamidopropyl betaine, cocamide MEA, cocamide DEA. Other embodiments of the invention are directed to a topical formulation comprising Portulaca oleracea extract, Sapindus mukorossi fruit extract, at least one of ammonium laureth sulfate, cocamidopropyl betaine, cocamide MEA, cocamide DEA for use in treating acne. According to some embodiments, the formulation is free of sodium dodecyl sulfate (SLS). According to some embodiments, the formulation is in a form of a cleansing gel.

[00024] According to some embodiments, the topical formulation includes one or more of anti-inflammatory ingredients, anti-bacterial ingredients, ingredients that regulate sebum secretion, skin hydration ingredients, analgesics, anti-irritant, anti-oxidants and any combination thereof.

[00025] According to some embodiments, the active ingredients in the topical formulation provide a synergistic effect in treating and/or preventing acne. According to further embodiments, the combination of at least one of the active ingredients with at least one of the other components in the formulation provides a synergistic effect in treating and/or preventing acne. The synergistic effect may be direct, in treating/preventing the condition, indirect, e.g., by enhancing the penetration of the formulation/active ingredients into the skin or lowering skin irritation, or both direct and indirect.

[00026] The use of zinc oxide may aid in the reduction of sebum levels. Kaolin may be used to absorb excessive oiliness and exudates from oily skin. Baicalin and Rheum palmatum decrease androgen receptor expression and therefore, may be used to decrease androgen mediated stimulation of sebaceous gland activity, resulting in decreased sebum production. Thus, the combination of the Rheum palmatum and Scutellaria baicalensis, or the active ingredient thereof baicalin, together with zinc oxide and/or kaolin or any other equivalent ingredients, synergistically reduces sebum secretion and absorbance of oils from the skin.

[00027] Hydroxyphenyl propamidobenzoic acid, a synthetic avenanthramide, may enhance the anti-inflammatory activity of the herbal mixture. Further, Rheum palmatum extract also presents anti-inflammatory activity specific to acne resulting from inhibition of cytokines such as IL-1 alpha. Thus, according to some embodiments, hydroxyphenyl propamidobenzoic acid, or any equivalent ingredient, and Rheum palmatum synergistically enhance the anti-inflammatory activity of the formulation.

[00028] Nordihydroguaiaretic acid and oleanolic acid may reduce hyperkeratosis, inhibit inflammation and reduce sebum secretion by inhibition of 5-alpha-reductase and control bacteria growth. Further, usnic acid is known to have anti bacterial activity and Hamamelis virginiana (witch hazel) water is known to have anti inflammatory properties. Such ingredients, or equivalent ones, may treat acne in a synergistic manner together with the herbal extracts that have anti-inflammatory activity, e.g., Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum indicum extract and Scutellaria baicalensis root extract or Baicalin. They may also treat acne synergistically when used together with extracts that regulate sebum secretion, e.g., Rheum palmatum extract, and Scutellaria baicalensis root extract or Baicalin. According to some embodiments, the above ingredients or equivalents thereof synergistically enhance anti-bacterial activity against Propionibacterium acne bacteria when used together with Portulaca oleracea extract. It is noted that the reduction in Propionibacterium acne is associated with a reduction in inflammatory mediators and clinical improvement of acne. The above ingredients may further synergistically enhance wound healing activities when used together with Portulaca oleracea extract and Rheum palmatum extract.

[00029] Hippophae Rhamnoides oil (Sea buckthorn oil) may be used for wound healing. Thus, the combination thereof, or of any other equivalent ingredient, together with herbal extracts that have wound healing properties, such as Portulaca oleracea extract and Rheum palmatum extract, may provide a synergistic effect in relieving the appearance of acne and reducing scar formation. Hippophae Rhamnoides oil and Hamamelis virginiana (Witch Hazel) water are further known to be antioxidants. Therefore, the combination thereof, or of any other equivalent ingredient, synergistically enhances the antioxidant activity of the herbal extracts, which reduces acne severity and symptoms.

[00030] Chamomilla recutita (Matricaria) flower extract has anti-inflammatory activity and reduces irritation in the skin. Thus, the combination thereof, or of any other equivalent ingredient with the herbal extract mixture may synergistically reduce inflammation and skin irritation in acne patients. Further, according to some embodiments, the formulation further comprises salicylic acid that may cause skin irritation. The addition of Chamomilla recutita (Matricaria) flower extract may reduce such skin irritation as well. Allantoin and alpha-bisabolol may also be added in order to reduce skin irritation, including irritation caused by the addition of salicylic acid.

[00031 ] According to further embodiments, the topical formulation further comprises salicylic acid. According to further embodiments, the topical formulation further comprises at least 0.3% w/w salicylic acid. According to further embodiments, the topical formulation further comprises at least 0.4% w/w salicylic acid. According to further embodiments, the topical formulation further comprises at least 0.5% w/w salicylic acid. According to further embodiments, the topical formulation further comprises about 1.0% w/w salicylic acid. According to further embodiments, the topical formulation further comprises salicylic acid in the range of 0.4-2.5% w/w. According to further embodiments, the topical formulation further comprises salicylic acid in the range of 0.5-2.0% w/w. According to further embodiments, the topical formulation further comprises salicylic acid in the range of 0.5- 1.5% w/w. According to further embodiments, the topical formulation further comprises salicylic acid in the range of 0.5-1.0% w/w. According to further embodiments, the topical formulation further comprises salicylic acid in the range of 1.25-2% w/w.

[00032] According to further embodiments, the topical formulation further comprises benzyl peroxide. According to further embodiments, the topical formulation further comprises at least 1.5% w/w benzyl peroxide. According to further embodiments, the topical formulation further comprises at least 2.0% w/w benzyl peroxide. According to further embodiments, the topical formulation further comprises at least 2.5% w/w benzyl peroxide. According to further embodiments, the topical formulation further comprises benzyl peroxide in the range of 1.5-12.0% w/w. According to further embodiments, the topical formulation further comprises benzyl peroxide in the range of 2.0-1 1.0% w/w. According to further embodiments, the topical formulation further comprises benzyl peroxide in the range of 2.5-10.0% w/w.

[00033] According to some embodiments, the pH of the topical formulation is between about 3.0-5.0. According to further embodiments, the pH of the topical formulation is between about 3.5-4.5. According to further embodiments, the pH of the topical formulation is between about 2.5-6.0. According to some embodiments, the pH of the topical formulation is between about 6.0-9.0. According to further embodiments, the pH of the topical formulation is between about 7.0-8.0. According to further embodiments, the pH of the topical formulation is between about 6.5-8.5.

[00034] According to some embodiments, the combined concentration of the herbal extracts in the formulation is at least 0.75%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is at least 0.9%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is at least 1.0%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is between about 0.8-1 .2%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is at least 8.0%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is at least 9.0%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is at least 10.0%. According to some embodiments, the combined concentration of the herbal extracts in the formulation is between about 9.0-1 1 %.

[00035] According to some embodiments, the amount of each herbal extract in the formulation is about 0.3%. According to some embodiments, the amount of each herbal extract in the formulation is in the range of about 0.25-0.35%. According to some embodiments, the amount of each herbal extract in the formulation is in the range of about 0.2-0.4%.

[00036] According to some embodiments, the formulation comprises at least 0.075% baicalin. According to some embodiments, the formulation comprises at least 0.085% baicalin. According to some embodiments, the formulation comprises at least 0.095% baicalin. According to further embodiments, according to further embodiments, the face cream formulation comprises at least 0.1 % baicalin. According to some embodiments, a spot treatment formulation comprises at least 1.0% baicalin. According to some embodiments, the concentration of the herbal extracts in the face cream is about 1 .0- 1.6%. According to some embodiments, the concentration of the herbal extract in the spot ointment is about 9.0-1 1 .0%. Using routine methods, the formulations of the present invention may be formulated into a variety of preparations, depending on the intended use. These preparations include, but are not limited to, topical skin compositions for medical use and topical skin cosmetic compositions.

[00037] As topical skin compositions for medical use and topical skin cosmetic compositions, many forms of gels, ointments, soaps, creams and lotions may be used. The formulation may be applied in any suitable manner, i.e., by hand, spatula, spray or pad.

[00038] The formulation of the invention may be in the form of a face cream, spot treatment, or cleansing gel. The formulation of the invention may be applied to the entire area of the skin affected by the acne or locally to each sore. The formulations of the invention show high dermal compatibility and low irritation behavior when applied to human skin. According to some embodiments, the formulations are applied to the body and subsequently remove therefrom, e.g., by washing with water.

[00039] When the topical compositions of the present invention are used as cosmetic compositions, cosmetic or dermatological acceptable ingredients may be optionally incorporated in arbitrary combinations as desired and determined in accordance by a person skilled in the art. According to some embodiments, the compositions may include oils, fats, waxes, detergents, conditioners, pH modifiers, preservatives, solvents, viscosity modifiers, colorants, perfumes, dyestuffs and the like. [00040] The composition may be in a form of oil-in-water, water-in-oil, water-in-oil-in- water, and oil-in-water-in-silicone emulsions, a cream, an ointment, an aqueous solution, a lotion, a soap, a paste, a foam, an emulsion, a gel, a salves, an oil, a wash, a conditioners or an aerosol.

[00041 ] According to an embodiment of the invention, the compositions of the invention are administered once a day. According to other embodiments, the compositions are administered twice a day, three times a day or more.

[00042] According to an embodiment of the invention, the composition is administered chronically.

[00043] According to some embodiments of the invention, the composition is administered for about 10 days or more, 20 days, 30 days, 60 days, 90, 120 days or more.

[00044] In some embodiments of the invention, the composition further comprises cleaning agents or detergents that are typically anionic, cationic, non-ionic or amphoteric surfactants. Typical anionic surfactants are carboxylates, sulfonates, sulfates or phosphates, e.g. fatty acid soaps, salts of lauryl sulfate and salts of lauryl ether sulfate. Examples of cationic surfactants are aliphatic mono, di and polyamines derived from fatty and rosin acids, amine oxides, ethoxylated alkyl amines and imidazolines. Examples of non-ionic surfactants are polyoxyethylene surfactants, alkylphenol ethoxylates, carboxylic acid esters, e.g., mono and diglycerides, polyoxyethylene esters and fatty acid diethanolamine condensates. Amphoteric surfactants are those containing combinations of the anionic and cationic groups described above, particularly those containing both acid carboxyls and basic nitrogen groups. Typical amphoteric surfactants are imidazolines and betaines, e.g., lauric and myristic imidazolines and betaines, and amidopropylbetaines.

[00045] The topical pharmaceutical compositions may also comprise a suitable emulsifier which refers to an agent that enhances or facilitates mixing and suspending oil- in-water or water-in-oil. The emulsifying agent used herein may consist of a single emulsifying agent or may be a nonionic, anionic, cationic or amphoteric surfactant or blend of two or more such surfactants; preferred for use herein are nonionic or anionic emulsifiers. Such surface-active agents are described in "McCutcheon's Detergent and Emulsifiers," North American Edition, 1980 Annual published by the McCutcheon Division, MC Publishing Company, 175 Rock Road, Glen Rock, N.J. 07452, USA.

[00046] The CTFA Cosmetic Ingredient Handbook, Second Edition (1992) describes a wide variety of non-limiting cosmetic ingredients commonly used in the skin care industry, which are suitable for use in the compositions of the present invention. Examples of these ingredient classes include: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, skin sensates, astringents, etc. (e.g. , clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, anti-caking agents, antifoaming agents, antimicrobial agents (e.g., iodopropyl butylcarbamate), antioxidants, binders, biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or materials, e.g., polymers, for aiding the film-forming properties and substantivity of the composition (e.g., copolymer of eicosene and vinyl pyrrolidone), opacifying agents, pH adjusters, propellants, reducing agents, sequestrants, skin- conditioning agents (e.g., humectants, including miscellaneous and occlusive), skin soothing and/or healing agents (e.g. , panthenol and derivatives (e.g., ethyl panthenol), aloe vera, pantothenic acid and its derivatives, allantoin, bisabolol, and dipotassium glycyrrhizate), skin treating agents, thickeners, and vitamins and derivatives thereof.

[00047] Other dermatological disorders which may be treated or prevented by embodiments of the formulation are for example, without being limited dandruff and oily skin conditions

[00048] The term "about" refers to ±10%. The term % w/w, relates to the weight of a particular ingredient as a percent of the weight of the entire formulation.

[00049] The expression "dermatologically acceptable carrier" as used herein, means a carrier that is compatible with the skin, scalp, hair, nail and the like.

[00050] The term "preventing" refers to keeping a disease, disorder or condition from occurring in a subject. In some cases the subject may be at risk for developing the disease, but has not yet been diagnosed as having the disease. In some instances, the term "preventing" refers to preventing the next cycle of the disease from occurring.

[00051 ] The plant extracts used herein may be purified by the use of a polar solvent (i.e. polar extract) such as, ethyl alcohol (ethanol), butyl alcohol (butanol), methanol, water or proanol, propylene glycol, butylene glycol, glycerin. The polar extracts of the present invention may comprise any percentage of a polar solvent. .

[00052] Alternatively, the plant extracts may be purified by the use of a non-polar solvent (i.e. non-polar extract) such as, without being limited to, isooctane. The non- polar extracts of the present invention may comprise any percentage of non-polar solvents.

[00053] Typically, hydrophobic molecules tend to be non-polar and thus non-polar solvents are used. Hydrophilic molecules tend to be polar and dissolve by water and/or other polar substances. [00054] The active ingredients can be concentrated in the extract via affinity chromatography, mass chromatography and the like.

[00055] Typically, the plant extract of the present invention is an aqueous extract. In order to obtain a purified plant extract (e.g. with reduced levels of organic salts and/or heavy metals and/or starch in the plant extract), the aqueous plant extract is typically further purified using a resin chromatography such as a macroporous resin or other chromatography methods. Glycerin, propandiol, butylene glycol or propylene glycol may be added to the water extracts to elevate the solubility of the extract, to elevate the penetration ability into the skin and to further preserve the extract. The extracts may contain also a preservative.

[00056] Thus, according to another embodiment, there is provided a method of preparing a composition comprising concentrated herbal extracts for treating and/or preventing acne, the method comprising: (a) subjecting a plant to x1-10 volumes of water to produce an extract of the plant; and (b) reducing the amount of impurities in the plant extract using a macroporous resin which results in an elevated content of the active ingredients present in the plant extract.

[00057] According to some embodiments, the formulation comprises any additional ingredients, including solvents, emollients, moisturizers, conditioners, viscosity builders, skin calmers, emulsifiers, pH adjusters, preservatives, antioxidants, viscosity increasing agents, perfumes, humectants, anti-acne agents, stabilizers and detergents.

EXAMPLES

Example 1

Formulation for treating/preventing acne (spot ointment)

Table I

INCI Name Activity

Aqua Solvent

Kaolin 15% Sebum absorbent

Titanium Dioxide 10% sebum absorbent

Alcohol SDA#40 Solvent

Cetearyl Alcohol Self Emulsified

Wax

Ceteareth-33

Hexylene Glycol Moisturizer Propylene Glycol Moisturizer

Portulaca Oleracea Extract 3% Botanical extract

Rheum Palmatum Extract 3% Botanical extract

Chrysanthemum Indicum Extract Botanical extract

3%

Butylene Glycol Skin conditioner

PEG-60 Almond Glycerides

Caprylyl Glycol

Glycerin

Carbomer

Nordihydroguaiaretic Acid

Oleanolic Acid

C12-15 AlkyI Benzoate Emollient

Cetyl Alcohol Thickener

Zinc Oxide Skin Calmer

HippophaeRhamnoides Oil 1 % Skin Conditioner

ScutellariaBaicalensis Root Botanical extract Extract 1 %

Dimethicone Emollient

Butylene Glycol Skin Calmer

Pentylene Glycol

HydroxyphenylPropamidobenzoic

Acid

Triethanolamine Ph -Adjuster

Imidazolidinyl Urea Preservative

Acrylates/ C10-30 AlkyI Acrylate Emulsion Stabilizer Crosspolymer

Carbomer

Usnic Acid Active ingredient

Fragrance Perfume Methylchloroisothiazolinone ί Preservative

Mixture

Methylisothiazolinone

Example 2

Formulation for treating/preventing acne (face cream)

Ta ble ll

INCI Name Reason for Use

Aqua Solvent

Alcohol SDA#40 Solvent

Cyclopentasiloxane Skin conditioning agent

Glycerin Moisturizer

Cetyl Alcohol Emulsifying agent

Viscosity increasing agent

DiisopropylAdipate Emollient

Polyethylene Silky feeling

Polyacrylate-13 Emulsifier

Polyisobutene

Polysorbate 20

Cetearyl Alcohol Viscosity

increasing agent

Salicylic Acid Antiacne agent

Butylene Glycol Antiacne mix

PEG-60 Almond Glycerides

Caprylyl Glycol

Glycerin

Carbomer

Nordihydroguaiaretic Acid Oleanolic Acid

Steareth-2 Emulsifier

Dipotassium Glycyrrhizate Skin Calmer

Caprylic/Capric Triglyceride Skin conditioning agent

Dimethicone Skin conditioning agent

Steareth-21 Emulsifier

Triethanolamine pH Adjuster

Tocopheryl Acetate (Vitamin E) Antioxidant

Cyclomethicone Emollient

Dimethiconol

Portulaca Oleracea Extract 0.3% Botanical extract

Rheum Palmatum Root Extract Botanical extract 0.3%

Chrysanthemum Indicum Flower Botanical extract Extract 0.3%

ChamomillaRecutita (Matricaria) Skin conditioning Flower Extract 0.3% agent

HamamelisVirginiana (Witch Skin conditioning Hazel) Water 0.3% agent

Xanthan Gum Viscosity

increasing agent

ScutellariaBaicalensis Root Botanical extract Extract 0.1 %

Allantoin Skin protectant oBisabolol Skin conditioning agent

Fragrance: Alpha Isomethyl Fragrance lonone, Benzyl Benzoate, Benzyl

Salicylate, Citronellol, Geraniol,

Hydroxyisohexyl-3-Cyclohexene

Carboxaldehyde

Disodium EDTA Chelating agent The pH of the above face cream is between about 3.5-4.5.

Example 3

Formulation for treating/preventing acne (face cream)

Table III

Example 4

Formulation for treating/preventing acne (cleansing gel)

Table IV

Previous and less effective

formulation New and more effective formulation

Plants extracts Portulaca oleracea Extract, Portulaca oleracea Extract, Sapindus

Sapindus mukorossi Fruit Extract mukorossi Fruit Extract

Additional Guaiazulene Without Guaiazulene

Active

ingredients for

treatment

enhancement

Surfactants Contains SLS SLS free Ammonium Laureth Sulfate,

Cocamidopropyl Betaine, Cocamide MEA, Cocamide DEA.

Example 5

Formulation for treating/preventing acne (spot treatment)

Table V

Example 6

Comparison between two face cream formulations

[00058] A comparison between treatments with two face creams was performed. The first face cream has the ingredients as detailed in Table II above while the second face cream, less effective, is as detailed in Table VI below:

Table VI

INCI Name % Reason for Use

Deionized Water Solvent

Caprylic / Capric Triglyceride Emollient Peg -8 Moisturizer

Cetyl Alcohol Viscosity Builder

Hydrolyzed Algin&

Zinc Sulfate Skin Conditioner

Stearic Acid Emulsifing Wax

Triethanolamine Ph -Adjuster

Triglyceride & Skin Calmer

LaminariaOchroleuca Extract

Butylene Glycol & Skin Conditioner

10 - Hydroxydecanoic Acid

DipotassiumGlycyrrhizinate Skin Calmer

Palmitoyl Hydrolyzed Wheat Skin Conditioner Protein

Sodium acrylate

Caprylolyl Glycine Skin Conditioner

Acetylated Lanolin Emollient

Phenoxyethanol&

Methylparaben& Preservative Mixture

Ethylparaben&

Butylparaben&

Propylparabens

Isobutylparaben

Dimethicone Antifoam

Rheum Palmatum Root Extract 0.15 Botanical Extract

Portulaca Oleracea Extract 0.15

Chrysanthemum Sinensis Flower 0.15

Extract

Acrylates/ C10-30Alkyl Acrylate Emulsifier

Crosspolymer Tocopheryl Acetate Antioxidant

ScutellariaBaicalensis Root 0.05

Extract

Fragrance Perfume

Guaiazulene Skin Calmer

Polysorbate -20 Emulsifier

Mcthylchloroisothiazolinone Preservative

Methylisothiazolinone Preservative

The pH of the face cream in Table VI is between about 6.0-7.5.

[00059] Six patients, ages 28.7±7.7 applied the creams on their face for six to seven days, wherein the first cream was applied to half the face and the second cream was applied to the other half of the face.

[00060] An evaluation questionnaire was filled out by the participants at the end of the testing period, wherein the following criteria were included in the questionnaire:

1. Effect of the product on the number of pimples;

2. Effect of the product on the severity of pimples;

3. Effect of the product on skin oiliness;

4. Effect of the product on skin redness;

5. Effect of the product on black heads;

6. General appearance;

7. General evaluation of the product; and

8. Product texture.

[00061] Criteria 1-5 were evaluated as having: no effect, minimal effect or significant effect; and criteria 6-8 were evaluated as being: bad, OK, good and excellent.

[00062] The results of the treatment study are presented in Figures 1A, 1 B, 1 C and 1 D.

[00063] A comparison between Figures 1A and 1 C, as well as between Figures 1 B and 1 D shows that the treatment with the first cream (detailed in Table II and related to in Figures 1 A and 1 B) was more effective and more satisfactory than the treatment with the second cream (detailed in Table VI and related to in Figures 1 C and 1 D) in all criteria tested, aside from the effect of the product on black heads, which was similar in both products. Example 7

Comparison between two spot treatment formulations

[00064] A comparison between treatments with two spot treatment formulations was performed. The first spot treatment formulation has the ingredients as detailed in Table I above, while the second face cream is as detailed in Table VII below:

Table VII

INCI Name Reason for Use

Deionized Water Solvent

Kaolin filler

Titanium Dioxide filler

Alcohol denat.

10 -Hydroxydeeanoic Acid

Cetearyl Alcohol emulsifier

Ceteareth-33

Portulaca Oleracea Extract Botanical Mixture

Rheum Palmatum Root

Extract

Chrysanthemum indicum

Flower Extract

Propylene Glycol Moisturizer

Hexylene Glycol Moisturizer

C12-15 Alkyl Benzoate Emollient

HippophaeRhamnoides Oil Skin Conditioner

Palmitoyl Hydrolyzed Wheat Skin Calmer

Protein

Zinc Oxide Skin Calmer

ScutellariaBaicalensis Root Skin Calmer

Extract Botanical extract

Ethoxydiglycol Usnic Acid

Dimethicone Emollient

Phenoxyethanol& Preservative

Mixture

Methyl pa raben&

Ethylparaben

Butylparaben&

Propylparaben

Isobutylparaben

Acrylates Copolymer Emulsion

Stabilizer

Methylchloroisothiazolinone Preservative

(and)

Methylisothiazolinone

Fragrance

The pH of the formulation presented in Table VII is between about 6-7.

[00065] Five patients, ages 44.8±10.3 applied the spot treatment formulations on their face twice a day for seven days, wherein the first formulation was applied to half the face and the second formulation was applied to the other half of the face. The spot treatment formulation is considered to be a thick cream or an ointment.

[00066] An evaluation questionnaire was filled out by the participants at the end of the testing period, wherein the following criteria were included in the questionnaire:

1. Effect of the product on the number of pimples;

2. Effect of the product on the severity of pimples;

3. Effect of the product on skin redness;

4. General appearance;

5. General evaluation of the product; and

6. Product texture.

[00067] Criteria 1-3 were evaluated as having: no effect, minimal effect or significant effect; and criteria 4-6 were evaluated as being: bad, OK, good and excellent.

[00068] The results of the treatment study are presented in Figures 2A, 2B, 2C and 2D. A comparison between Figures 2A and 2C, as well as between Figures 2B and 2D shows that the treatment with the first cream (detailed in Table I and related to in Figure 2A and 2B) was more effective and more satisfactory than the treatment with the second cream (detailed in Table VII and related to in Figures 2C and 2D) in all criteria tested, aside from the effect of the product on redness, which was similar in both products.

Example 8

Comparison of a combination of an herbal mixture and 0.5% salicylic acid .vs. 0.5% salicylic acid

[00069] 28 individuals afflicted with acne were treated for 12 days with a formulation comprising an herbal mixture+0.5% salicylic acid on half the face, whereas the other half of the face was treated only with 0.5% salicylic acid. The herbal mixture contained 1.5% Portulaca oleracea extract, 1.5% Rheum palmatum extract, 1.5% Chrysanthemum Indicum extract and 0.5% Scutellaria baicalensis root extract (baicalin).

[00070] The results are presented in Figure 3 show the percentage of reduction in inflammatory acne lesions when treated only with salicylic acid and when treated with a combination of salicylic acid and the herbal mixture detailed above. As presented in Fig. 3, the salicylic acid alone reduced only about 17% of the lesions, whereas the herbal mixture together with the salicylic acid reduced 32% of the inflammatory lesions.

Claims

What is claimed is:

1. A topical formulation comprising Portulaca oleracea extract, Rheum palmatum extract, Chrysanthemum indicum extract and Scutellaria baicalensis root extract or its active ingredient Baicalin, together with nordihydroguaiaretic acid and oleanolic acid.

2. The topical formulation according to claim 1 , for use in treating or preventing acne.

3. The topical formulation according to claim 1 , further comprising one or more of dipotassium glycyrrhizate, Chamomilla recutita (matricaria) flower extract and Hamamelis virginiana (witch hazel).

4. The topical formulation according to claim 1 , further comprising one or more of salicylic acid, allantoin and obisabolol.

5. The topical formulation according to claim 1 , further comprising one or more of kaolin, zinc oxide, hippophae rhamnoides oil, usnic acid, hydroxyphenyl propamidobenzoic acid, titanium dioxide.

6. The topical formulation according to claim 1 , further comprising one or more of imidazolidinyl urea, methylchloroisothiazolinone and methylisothiazolinone.

7. The topical formulation according to any one of claims 3 and 4, wherein the formulation has a pH in the range of about 3.5-4.5.

8. The topical formulation according to claim 5, the formulation has a pH in the range of about 7.0-8.0.

9. A topical formulation comprising Portulaca oleracea extract, Sapindus mukorossi fruit extract and at least one of ammonium laureth sulfate, cocamidopropyl betaine, cocamide MEA, cocamide DEA.

10. The topical formulation according to claim 9, for use in treating or preventing acne.

1 1 . The topical formulation according to any one of claims 1 -4, wherein the amount of the salicylic acid is in the range of 0.5-2.0% w/w.

12. The topical formulation according to claim 1 , wherein the formulation is a face cream or a spot ointment.

13. The topical formulation according to claim 9, wherein the formulation is a cleansing gel.

14. The topical formulation according to 12, wherein the combined concentration of the herbal extracts is at least 0.9% w/w when the topical formulation is a face cream.

15. The topical formulation according to claim 12, wherein the combined concentration of the herbal extracts is at least 9.0% w/w when the topical formulation is a spot ointment.

16. The topical formulation according to claim 12, comprising at least 0.075% baicalin when the topical formulation is a face cream and at least 0.9% when the formulation is a spot ointment.

17. The topical formulation according to claim 12, wherein the amount of each herbal extract is about 3%, when the formulation is a spot treatment formulation.

18. The topical formulation according to 12, wherein the amount of each herbal extract is about 0.3%, when the formulation is a face cream formulation.

19. The topical formulation according to claim 1 , wherein the formulation provides a synergistic effect regarding sebum secretion reduction, absorbance of skin oils, anti-inflammatory activity, anti-bacterial activity, wound healing properties, anti- oxidative activity, skin irritation reduction, skin absorbance of the formulation, or any combination thereof.

20. A method of treating acne comprising the step of topically applying the topical formulation of claim 1 to a subject in need.