Compositions Comprising Carum Carum and Rosemary Extracts and Methods of Using Them

Abstract

Compositions are provided that include caraway seed extract, rosemary extract, and a pharmaceutically and / or cosmetically acceptable carrier, as well as methods of using the same.

Description

[Technical Field]

[0001] The present invention relates to a composition for topically reducing inflammation. More specifically, the present invention relates to a composition comprising caraway seeds and rosemary extract for reducing inflammation of the skin and / or mucous membranes. [Background technology]

[0002] A wide variety of skin care actives suitable for use in personal care compositions are known. Examples of such skin care actives include olive leaf extracts (e.g., Leaf extract of Olea europea rich in oleuropeine, products from it, their application as medicines and compositions containing them. Combes, Georges; Escaut, Alexandre. Fr. Demande, FR 2507477(A1) 19821217, 1982; Gonzalez M, et al., Hypoglycemic activity of olive leaf, Planta Med December 1992; 58(6):513-515; Use of an extract from the leaves of Olea europea as an antiradical agent. Amari, Giorgio. Eur. Pat. Appl. (1999), EP 937455(A1) 19990825; Fehri B, et al.), which have been described to exhibit hypotensive and hypoglycemic activity, antiradical properties for food and cosmetics, and anti-inflammatory activity when given via the oral route. al. Olea europaea L.: stimulant, anti-ulcer, and anti-inflammatory effects. See Boll Chim Farm (1996) 135(1):42-49), saigesbeckia (holy herb), which is used as a remedy for chills, rheumatism, renal colic, and, together with glycerin, as a treatment for ringworm, Lignum sappan (sobok), which is used to promote circulation and remove congestion, and to soothe swelling and relieve pain, and feverfew, which is recognized to have significant pharmacological effects when taken orally and is used as a general fever reducer.Other skin care actives include oil extracts such as Boswellia serrata oil extract (frankincense), which has been described to exhibit anti-tumor and anti-arthritic properties, and oat oil extract, which has been described to exhibit anti-irritant and antioxidant properties.

[0003] There is a continuing need to develop combinations of skin care actives to effectively treat, reduce, and / or prevent inflammation of the skin from any of a variety of sources. Although there may be a variety of actives that tend to exhibit anti-inflammatory properties, it is generally difficult, if not impossible, to predict such combinations of actives that will exhibit unexpectedly high synergistic anti-inflammatory properties and effectiveness in reducing inflammation.

[0004] Additionally, in certain applications, it may be desirable to use relatively small amounts of an active for cost reasons, to reduce undesirable color or odor associated with a particular active, for stability reasons, etc. However, many actives or combinations thereof tend to have relatively little or no effectiveness in reducing inflammation when applied in relatively small amounts. Summary of the Invention [Problem to be solved by the invention]

[0005] Thus, there is a continuing need for combinations of skin care actives that exhibit relatively high, synergistic anti-inflammatory properties and effectiveness, as well as certain combinations that may be even more effective even in relatively small amounts. [Means for solving the problem]

[0006] Thus, one aspect of the present invention is Caraway seed extract, Rosemary extract, a pharmaceutically and / or cosmetically acceptable carrier; The present invention relates to a composition comprising:

[0007] In one or more embodiments, the composition further comprises a material selected from the group consisting of surfactants, chelating agents, emollients, moisturizers, conditioners, preservatives, opacifiers, fragrances, and combinations of two or more thereof. In some embodiments, the carbuncle seed extract and rosemary extract each independently comprise a polar extract. In further embodiments, the carbuncle seed extract and rosemary extract both comprise a polar extract. In one or more embodiments, the polar extract has been extracted with one or more solvents selected from the group consisting of C1-C8 alcohols, C1-C8 polyols, C1-C8 glycols, and combinations thereof. In some embodiments, the carbuncle seed extract and rosemary extract each independently comprise one or more solvents including ethanol and water. In one or more embodiments, one or both of the carbuncle seed extract and rosemary extract are substantially free of non-polar extracts. In some embodiments, one or both of the carbuncle seed extract and rosemary extract are substantially free of essential oils. In one or more embodiments, the composition is in the form of a tablet, pill, or capsule. In some embodiments, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid cleanser, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. In one or more embodiments, the caraway seed extract and rosemary extract are present in the composition at a combined concentration of about 0.1 to about 20% by weight of the total composition. In some embodiments, the caraway seed extract and rosemary extract are present in a ratio of about 1:2 to about 1:100. In one or more embodiments, the caraway seed extract is present at a concentration of about 50 to about 350 μg / mL, and the rosemary extract is rosemary leaf extract present at a concentration of about 0.5 to about 25 μg / mL. In some embodiments, the caraway seed extract is present at a concentration of about 50 μg / mL and the rosemary leaf extract is present at a concentration of about 0.5 to about 5 μg / mL.

[0008] Another aspect of the invention is a method for reducing inflammation, comprising: The present invention relates to a method comprising administering to a patient in need of reducing inflammation a therapeutically effective dose of a composition comprising caraway seed extract and rosemary extract.

[0009] In one or more embodiments, the inflammation comprises CCR2 receptor-mediated inflammation. In some embodiments, the caraway seed extract and the rosemary leaf extract each independently comprise a polar extract. In further embodiments, the caraway seed extract and the rosemary extract both comprise a polar extract. In one or more embodiments, the polar extract has been extracted with one or more solvents selected from the group consisting of C1-C8 alcohols, C1-C8 polyols, C1-C8 glycols, and combinations thereof. In some embodiments, one or both of the caraway seed extract and the rosemary leaf extract are substantially free of non-polar extracts. In one or more embodiments, one or both of the caraway seed extract and the rosemary leaf extract are substantially free of essential oils. In some embodiments, the composition is applied to the surface of the patient's skin. In one or more embodiments, the composition is applied to the patient's mucosa. In some embodiments, the composition is administered in the form of a solution, suspension, lotion, cream, serum, gel, stick, spray, ointment, liquid cleanser, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. In one or more embodiments, the composition is administered orally. In some embodiments, the composition is administered in the form of a tablet, pill, or capsule. In one or more embodiments, the caraway seed extract and rosemary extract are present in the composition at a combined concentration of about 0.1 to about 20% by weight of the total composition. In some embodiments, the caraway seed extract and rosemary extract are present in a ratio of about 1:2 to about 1:100. In one or more embodiments, the caraway seed extract is present at a concentration of about 50 to about 350 μg / mL, and the rosemary extract is rosemary leaf extract present at a concentration of about 0.5 to about 25 μg / mL. In some embodiments, the caraway seed extract is present at a concentration of about 50 μg / mL and the rosemary leaf extract is present at a concentration of about 0.5 to about 5 μg / mL.

[0010] Yet another aspect of the present invention is a composition comprising: A caraway seed extract having a concentration of about 50 to about 350 μg / mL; a rosemary leaf extract having a concentration of about 0.5 to about 25 μg / mL; a pharmaceutically and / or cosmetically acceptable carrier; Including, The caraway seed extract and rosemary leaf extract are hydroalcoholic extracts, and the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid cleanser, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. In some embodiments, the caraway seed extract is present at a concentration of about 50 μg / mL, and the rosemary leaf extract is present at a concentration of about 0.5 to about 5 μg / mL.

[0011] These and other features and advantages of the present invention will become readily apparent from the detailed description that follows. DETAILED DESCRIPTION OF THE INVENTION

[0012] As used herein, "skin in need of reduced skin inflammation" refers to a portion or area of ​​a patient's skin that exhibits redness or erythema, edema, or is reactive or sensitive to external factors, including, but not limited to, sunlight (UV, visible, IR), microorganisms, air pollutants such as ozone, exhaust pollutants, chlorine and chlorine-generating compounds, tobacco smoke, cold, heat, soaps and detergents, cosmetics, and gemstones. Inflammatory disorders and associated conditions that may be treated or prevented by use of the compositions of the present invention include, but are not limited to, arthritis, bronchitis, contact dermatitis, atopic dermatitis, psoriasis, seborrheic dermatitis, lacquer and pest oak dermatitis, eczema, allergic dermatitis, polymorphous light eruption, inflammatory skin diseases, folliculitis, alopecia, poison ivy, insect bites, acne inflammation; irritation induced by external factors, including, but not limited to, chemicals, trauma, pollutants (e.g., cigarette smoke), and sun exposure; secondary conditions resulting from inflammation, including, but not limited to, xerosis, excess sebum, pruritus, post-inflammatory hyperpigmentation, scarring, etc. In one or more embodiments, inflammatory disorders and related conditions that may be treated or prevented using the methods of the present invention include arthritis, inflammatory skin diseases, contact dermatitis, allergic dermatitis, atopic dermatitis, polymorphous light eruption, irritation including erythema induced by external factors, acne inflammation, psoriasis, seborrheic dermatitis, eczema, poison ivy, poison oak, poison sumac, insect bites, folliculitis, alopecia, and secondary conditions.

[0013] As used herein, "cosmetically / dermatologically acceptable" means suitable for use in contact with tissue (e.g., skin or hair) without undue toxicity, incompatibility, instability, irritation, and / or allergic reaction, etc.

[0014] As used herein, the term "safe and effective amount" means an amount sufficient to induce the desired effect, but small enough to avoid serious side effects. A safe and effective amount of a compound, extract, or composition will vary depending, for example, on the age, health, and environmental exposure of the end user, the duration and nature of the treatment, the particular extract, ingredient, or composition used, the particular pharmaceutically acceptable carrier employed, and similar factors.

[0015] As used herein, "essential oil" refers to a distillation product obtained from a plant, preferentially via steam distillation, containing the characteristic aroma of the plant or the particular part of the plant from which it is obtained. In some embodiments, an essential oil is a concentrated hydrophobic liquid obtained from a plant that contains a mixture of volatile oils (e.g., including volatile aroma compounds).

[0016] As used herein, "essentially free" or "substantially free" of an ingredient means containing less than 0.1 weight percent, less than 0.01 weight percent, or none of the ingredient.

[0017] In order to provide a more precise description, some of the quantitative expressions shown herein are not modified with the term "about". Regardless of whether the term "about" is explicitly used or not, it is understood that all quantities given herein refer to actual given values, and also refer to approximations of such given values ​​that can be reasonably estimated based on ordinary skills in the art, including approximations based on experimental and / or measurement conditions of such given values.

[0018] To provide a more precise description, some quantitative expressions are recited herein as a range of about amount X to about amount Y. When a range is recited, it is understood that the range is not limited to the recited upper and lower limits, but includes the entire range of about amount X to about amount Y, or any amount or range within that range.

[0019] Therefore, one aspect of the present invention relates to a composition comprising caraway seed extract, rosemary extract, and a pharmaceutically and / or cosmetically acceptable carrier.Surprisingly, it has been found that such a composition comprising caraway seed extract and rosemary extract unexpectedly provides good anti-inflammatory properties.When combined, the extracts exhibit synergistic anti-inflammatory effects.All tested combinations of caraway seed extract and rosemary have been demonstrated to be synergistic (having a >1-fold increase from additive levels), and even some combinations have demonstrated a 1.5-fold or 2-fold increase.In fact, it has been demonstrated that one or both of the extracts may not provide significant anti-inflammatory results for a given marker, but when the two extracts are combined, they may exhibit even stronger anti-inflammatory properties.

[0020] Caraway Seed Extract Caraway, commonly known as caraway, is a biennial plant native to Asia, Europe and parts of Africa.As used herein, " caraway seed extract " refers to the extract of seeds from the plant.Any suitable method can be used to prepare the extract of caraway seed extract for use according to the present invention. Suitable extracts can be obtained using conventional methods, including, but not limited to, grinding, maceration, pressing, squeezing, grinding, centrifugation, and / or cold irrigation, stirring / distillation, microwave-assisted extraction, ultrasound, supercritical / subcritical CO2 compressed gas extraction with or without polar modifiers, pressurized solvent extraction, accelerated solvent extraction, surfactant-assisted pressurized hot water extraction, oil extraction, membrane extraction, Soxhlet extraction, gold finger distillation / extraction, and / or direct extraction from biomass by processes disclosed in, for example, U.S. Patent Nos. 7,442,391, 7,473,435, and 7,537,791 (Integrated Botanical Technologies, LLC), which are incorporated herein by reference, or by other methods such as solvent extraction. Specifically, extracts according to the present invention can be solvent-based extractions performed by grinding or macerating plant material in a solvent, typically an organic solvent such as alcohol, acetone, liquid carbon dioxide with or without polar modifiers, hexane, or chloroform. The resulting extract contains mainly non-polar compounds. The plant biomass can be completely separated in the extraction and cannot be used after extraction.

[0021] Any of a variety of solvents, including polar solvents, nonpolar solvents, or combinations of two or more thereof, may be used in methods involving solvent extraction. In one or more embodiments, a polar solvent is used. Suitable polar solvents include polar inorganic solvents such as water; polar organic solvents such as alcohols and corresponding organic acids, e.g., C1-C8 alcohols, including methanol, ethanol, propanol, butanol, etc.; organic acids, including acetic acid, formic acid, propanoic acid, etc.; polyols and glycols, including C1-C8 polyols / glycols, etc.; and combinations of two or more thereof. Suitable nonpolar solvents include nonpolar organic solvents, e.g., alkanes, including C1-C8 alkanes; cycloalkanes, including C1-C8 alkanes; alkyl ethers, including C1-C8 alkyl ethers; petroleum ether; ketones, including C1-C8 ketones; methylene chloride; ethyl acetate; xylene; toluene; chloroform; vegetable oil; mineral oil; and the like. In another embodiment, the extraction can be obtained by supercritical fluid extraction with or without the use of non-polar solvents as described above or polar modifiers such as C1-C8 alcohols, water, C1-C8 polyols / glycols, or C1-C8 organic acids.

[0022] In one or more embodiments, the extract is a polar extract. Polar extract means that the extract is produced by subjecting a plant or plant part to a polar solvent. In certain embodiments, the extract is prepared by pulverizing Carum carum seeds and extracting them with a polar solvent having a dielectric constant value of 1 to 100 at 20°C, specifically a dielectric constant value of 4 to 60 at 20°C, more specifically a dielectric constant value of 4 to 50 at 20°C, and even more specifically a dielectric constant value of 4 to 40 at 20°C. Examples of suitable polar solvents include C1-C8 alcohols, C1-C8 polyols / glycols, C1-C8 organic acids, water, and combinations of two or more thereof, having a dielectric constant value of 1-100, specifically 4-60, and more specifically 5-40 at 20°C, including, but not limited to, solvents and solvent combinations having the desired dielectric constant value as disclosed in, for example, "Dielectric Constants of Some Organic Solvent-Water Mixtures at Various Temperatures," Akerlof, Gosta; JACS, Vol. 54, No. 11 (Nov. 1932), pp. 4125-4139, incorporated herein by reference. In some embodiments, the polar extract is extracted using one or more C1-C8 alcohols, C1-C8 polyols, C1-C8 glycols, and combinations of two or more thereof. In one or more embodiments, the extract is extracted using one or more C1-C4 alcohols, C1-C4 polyols, and / or C1-C4 glycols. In some embodiments, the extract is prepared using a solvent including methanol, ethanol, or a combination thereof, with or without water. In one or more embodiments, the extract may be further purified by charcoal (also called activated carbon) treatment. In one or more embodiments, the extract is a hydroalcoholic extract (i.e., a mixture of alcohol in water). In some embodiments, the hydroalcoholic extract contains about 5% to 10% alcohol in water.

[0023] In some embodiments, the extracts of the present invention are prepared by pulverizing Carum carum seeds and extracting them with a solvent having a dielectric constant of about 1 to about 80 at 20°C, specifically about 2 to about 60 at 20°C, more specifically about 2 to about 40 at 20°C, and even more specifically about 2 to 35 at 20°C.

[0024] In some embodiments, the composition is essentially free of extracts of other non-seed parts of the carbuncle plant. In further embodiments, the composition is free of extracts of other non-seed parts of the carbuncle plant. In certain embodiments, the composition may include an extract from a cell culture of the carbuncle plant. In one or more embodiments, the carbuncle seed extract is substantially free of non-polar extracts. In further embodiments, the carbuncle seed extract is free of non-polar extracts. In some embodiments, both the carbuncle seed extract and the rosemary extract are substantially free of non-polar extracts. In further embodiments, both the carbuncle seed extract and the rosemary extract are substantially free of non-polar extracts. In one or more embodiments, the carbuncle seed extract is substantially free of essential oils. In one or more embodiments, the carbuncle seed extract is free of essential oils. In further embodiments, both the carbuncle seed extract and the rosemary extract are substantially free of essential oils. In yet further embodiments, neither caraway seed extract nor rosemary extract contains essential oils.In some embodiments, neither caraway seed extract nor rosemary extract contains substantially no volatile components.In some embodiments, neither caraway seed extract nor rosemary extract contains no volatile components.

[0025] Any suitable amount of caraway seed extract may be used in the topical compositions of the present invention. In one or more embodiments, the composition comprises greater than 0 to about 20% caraway seed extract. In some embodiments, the composition comprises about 0.0001 to about 20%, about 0.001 to about 10%, about 0.01 to about 5%, about 0.1 to about 5%, or about 0.2 to about 2% caraway seed extract. In one or more embodiments, the composition comprises greater than 0 to about 1%, about 0.0001 to about 1%, about 0.001 to about 1%, or about 0.01 to about 1% caraway seed extract. In some embodiments, the composition comprises about 1 to about 5%, specifically about 2 to about 5%, of caraway seed extract.

[0026] rosemary extract As used herein, the term "rosemary extract" refers to an extract from any of the aerial parts of the rosemary plant, such as one or more of the stems or leaves. In other embodiments, the composition is essentially free of extracts of other non-stem and / or non-leaf parts of rosemary.

[0027] Any suitable method for preparing an extract of rosemary for use in accordance with the present invention may be used. Suitable extracts can be obtained using conventional methods, including, but not limited to, crushing, maceration, pressing, squeezing, grinding, centrifugation, and / or cold irrigation, stirring / distillation, microwave-assisted extraction, ultrasound, supercritical / subcritical CO2 compressed gas extraction with or without polar modifiers, pressurized solvent extraction, accelerated solvent extraction, surfactant-assisted pressurized hot water extraction, oil extraction, membrane extraction, Soxhlet extraction, gold finger distillation / extraction, and / or direct extraction from the biomass, for example, by the processes disclosed in U.S. Patent Nos. 7,442,391, 7,473,435, and 7,537,791 (Integrated Botanical Technologies, LLC), which are incorporated herein by reference, or by other methods such as solvent extraction. Specifically, the extracts according to the present invention may be solvent-based extractions performed by grinding or macerating the plant material in a solvent, typically an organic solvent such as alcohol, acetone, liquid carbon dioxide with or without polar modifiers, hexane, or chloroform. The resulting extracts contained primarily non-polar compounds. The plant biomass may be completely separated in the extraction and cannot be used after extraction.

[0028] Any of a variety of solvents, including polar solvents, nonpolar solvents, or combinations of two or more thereof, may be used in methods involving solvent extraction. In one or more embodiments, a polar solvent is used. Suitable polar solvents include polar inorganic solvents such as water; polar organic solvents such as alcohols and corresponding organic acids, e.g., C1-C8 alcohols, including methanol, ethanol, propanol, butanol, etc.; organic acids, including acetic acid, formic acid, propanoic acid, etc.; polyols and glycols, including C1-C8 polyols / glycols, etc.; and combinations of two or more thereof. Suitable nonpolar solvents include nonpolar organic solvents, e.g., alkanes, including C1-C8 alkanes; cycloalkanes, including C1-C8 alkanes; alkyl ethers, including C1-C8 alkyl ethers; petroleum ether; ketones, including C1-C8 ketones; methylene chloride; ethyl acetate; xylene; toluene; chloroform; vegetable oil; mineral oil; and the like. In another embodiment, the extraction can be obtained by supercritical fluid extraction with or without the use of non-polar solvents as described above or polar modifiers such as C1-C8 alcohols, water, C1-C8 polyols / glycols, or C1-C8 organic acids.

[0029] In one or more embodiments, the extract is a polar extract. Polar extract means that the extract is produced by subjecting a plant or plant part to a polar solvent. In certain embodiments, the extract is prepared by finely grinding rosemary leaves and extracting them using a polar solvent having a dielectric constant value of 1 to 100 at 20°C, specifically a dielectric constant value of 4 to 60 at 20°C, more specifically a dielectric constant value of 4 to 50 at 20°C, and even more specifically a dielectric constant value of 4 to 40 at 20°C. Examples of suitable polar solvents include C1-C8 alcohols, C1-C8 polyols / glycols, C1-C8 organic acids, water, and combinations of two or more thereof, having a dielectric constant value of 1-100, specifically 4-60, more specifically 5-40 at 20°C, including, but not limited to, solvents and solvent combinations having the desired dielectric constant value as disclosed in, for example, "Dielectric Constants of Some Organic Solvent-Water Mixtures at Various Temperatures," Akerlof, Gosta; JACS, Vol. 54, No. 11 (Nov. 1932), pp. 4125-4139, incorporated herein by reference. In one or more embodiments, the polar extract is extracted using one or more C1-C8 alcohols, C1-C8 polyols, C1-C8 glycols, and combinations of two or more thereof. In some embodiments, the extract is extracted using one or more C1-C4 alcohols, C1-C4 polyols, and / or C1-C4 glycols. In one or more embodiments, the extract is prepared using a solvent including methanol, ethanol, or a combination thereof, with or without water. In some embodiments, the extract may be further purified by charcoal (also called activated carbon) treatment. In one or more embodiments, the extract is a hydroalcoholic extract (i.e., a mixture of alcohol in water). In some embodiments, the hydroalcoholic extract contains about 5% to 10% alcohol in water.

[0030] In one or more embodiments, the extract of the present invention is prepared by finely grinding rosemary leaves and extracting them using a solvent having a dielectric constant value of about 1 to about 80 at 20°C, specifically a dielectric constant value of about 2 to about 60 at 20°C, more specifically a dielectric constant value of about 2 to about 40 at 20°C, and even more specifically a dielectric constant value of about 2 to about 35 at 20°C.

[0031] In certain embodiments, the composition may comprise an extract from a cell culture of the aerial parts of a rosemary plant. In one or more embodiments, the rosemary extract is substantially free of non-polar extracts. In further embodiments, both the caraway seed extract and the rosemary extract are substantially free of non-polar extracts. In one or more embodiments, the rosemary extract is substantially free of essential oils. In one or more embodiments, the rosemary extract is free of essential oils. In further embodiments, both the caraway seed extract and the rosemary extract are substantially free of essential oils. In further embodiments, both the caraway seed extract and the rosemary extract are free of essential oils. In some embodiments, both the caraway seed extract and the rosemary extract are substantially free of volatile components.

[0032] Any suitable amount of rosemary extract may be used in the topical compositions of the present invention. In some embodiments, the composition comprises greater than 0 to about 20% rosemary extract. In one or more embodiments, the composition comprises from about 0.0001 to about 20%, from about 0.001 to about 10%, from about 0.01 to about 5%, from about 0.1 to about 5%, or from about 0.2 to about 2% rosemary extract. In some embodiments, the composition comprises from greater than 0 to about 1%, from about 0.0001 to about 1%, from about 0.001 to about 1%, or from about 0.01 to about 1% rosemary extract. In one or more embodiments, the composition comprises from about 1 to about 5%, specifically from about 2 to about 5%, rosemary extract.

[0033] Any suitable amount of caraway seed and rosemary extract can be used in the compositions of the present invention. In one or more embodiments, the compositions comprise a safe and effective amount of caraway seed extract and rosemary extract. Specifically, the amount of caraway seed and rosemary extract used may be selected to achieve the desired treatment of a given inflammatory condition. In some embodiments, the compositions comprise from about 0.0001 to about 20%, from about 0.001 to about 10%, from about 0.01 to about 5%, from about 0.1 to about 5%, or from about 0.2 to about 2% of caraway seed and rosemary extract, combined. In one or more embodiments, the compositions comprise from greater than 0 to about 1%, from about 0.0001 to about 1%, from about 0.001 to about 1%, or from about 0.01 to about 1% of caraway seed and rosemary extract, combined. In some embodiments, the composition comprises about 1 to about 5%, specifically about 2 to about 5%, of caraway seed and rosemary extracts combined. The caraway seed extract and rosemary extract are present in the composition in amounts that can vary depending on the endpoint associated with the desired benefit. For example, in some embodiments, particularly those in which CCR2 receptor binding is desired, the weight ratio of rosemary extract to caraway seed extract is about 1:9 to about 1:70, more specifically about 1:17 to about 1:35, and even more specifically about 1:35. In some embodiments, particularly those in which reduced interleukin 6 and 8 (IL-6 and IL-8) release is desired, the weight ratio of rosemary extract to caraway seed extract is about 1:2 to about 1:100, more specifically about 1:10 to about 1:100, and even more specifically about 1:100.

[0034] Carrier Any suitable carrier may be used in the composition. In some embodiments, the carrier is a cosmetically acceptable carrier. As will be appreciated by those skilled in the art, a cosmetically acceptable carrier includes a carrier suitable for use in contact with the body, particularly the skin, that is free of undue toxicity, incompatibility, instability, irritation, allergic reaction, etc. A safe and effective amount of carrier is about 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 98% by weight to about 85, 90, 95, 98, 99, 99.1, 99.5, or 99.9% by weight of the composition.

[0035] The carrier may be in a wide variety of forms. For example, but not limited to, carriers in the form of emulsions such as oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone are useful herein. These emulsions may cover a wide range of viscosities, for example, from about 100 cP to about 200,000 cP using a Brookfield RVT viscometer.

[0036] Examples of suitable cosmetically acceptable carriers include cosmetically acceptable solvents and materials for cosmetic solutions, suspensions, lotions, creams, serums, essences, gels, toners, sticks, sprays, ointments, liquid cleansers and bars, shampoos, hair conditioners, pastes, foams, mousses, powders, shaving creams, wipes, patches, strips, powered patches, microneedle patches, bandages, hydrogels, film-forming products, facial and skin masks, makeup, liquid drops, etc. These product types can comprise several types of cosmetically acceptable carriers, including, but not limited to, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids, liposomes, other encapsulation technologies, etc.

[0037] The following are non-limiting examples of carriers. Other carriers may be formulated by those skilled in the art. In one embodiment, the carrier comprises water. In a further embodiment, the carrier may further comprise one or more aqueous or organic solvents. Examples of organic solvents include, but are not limited to, dimethyl isosorbide, isopropyl myristate, cationic, anionic, and nonionic surfactants, vegetable oils, mineral oils, waxes, gums, synthetic and natural gelling agents, alkanols, glycols, and polyols. Examples of glycols include, but are not limited to, glycerin, propylene glycol, butylene glycol, pentalene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, capryl glycol, glycerol, butanediol, and hexanetriol, as well as copolymers or mixtures thereof. Examples of alkanols include, but are not limited to, those having from about 2 carbon atoms to about 12 carbon atoms (e.g., from about 2 carbon atoms to about 4 carbon atoms), such as isopropanol and ethanol. Examples of polyols include, but are not limited to, those having from about 2 carbon atoms to about 15 carbon atoms (e.g., from about 2 carbon atoms to about 10 carbon atoms), such as propylene glycol. The organic solvent may be present in the carrier in an amount of from about 1 percent to about 99.99 percent (e.g., from about 20 percent to about 50 percent) based on the total weight of the carrier. Water may be present in the carrier in an amount of from about 5% to about 95% (e.g., from about 50% to about 90%) based on the total weight of the carrier (prior to use). Solutions can contain any suitable amount of solvent, including from about 40% to about 99.99%. Some solutions contain from about 50% to about 99.9%, from about 60% to about 99%, from about 70% to about 99%, from about 80% to about 99%, or from about 90% to about 99% solvent.

[0038] A lotion can be made from such a solution. The lotion typically contains at least one emollient in addition to the solvent. The lotion can contain about 1% to about 20% (e.g., about 5% to about 10%) of the emollient and about 50% to about 90% (e.g., about 60% to about 80%) of water.

[0039] Another type of product that can be formulated from a solution is a cream, which typically contains about 5% to about 50% (e.g., about 10% to about 20%) emollient and about 45% to about 85% (e.g., about 50% to about 75%) water.

[0040] Yet another type of product that can be formulated from a solution is an ointment. Ointments can contain a simple base of animal, vegetable, or synthetic oils, or a semi-solid 10-carbon hydrocarbon. Ointments can contain about 2% to about 10% of an emollient and about 0.1% to about 2% of a thickening agent.

[0041] The compositions useful in the present invention can also be formulated as emulsions. When the carrier is an emulsion, about 1% to about 10% (e.g., about 2% to about 5%) of the carrier contains an emulsifier. The emulsifier may be nonionic, anionic, or cationic.

[0042] Lotions and creams can be formulated as emulsions. Such lotions typically contain 0.5% to about 5% emulsifier, and such creams typically contain about 1% to about 20% (e.g., about 5% to about 10%) emollient. They contain about 20% to about 80% (e.g., about 30% to about 70%) water and about 1% to about 10% (e.g., about 2% to about 5%) emulsifier.

[0043] Single-phase emulsion skin care preparations, such as lotions and creams, of the oil-in-water and water-in-oil types, are well known in the art and are useful in the present invention.Multiple-phase emulsion compositions, such as water-in-oil-in-water or oil-in-water-in-oil types, are also useful in the present invention.In general, such single-phase or multi-phase emulsions contain water, emollients, and emulsifiers as essential ingredients.

[0044] The compositions of the present invention can also be formulated as gels (e.g., aqueous, alcohol, alcohol / water, or oil gels using a suitable gelling agent). Suitable gelling agents for aqueous and / or alcoholic gels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (such as mineral oil) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymers and hydrogenated ethylene / propylene / styrene copolymers. Such gels typically contain from about 0.1% to about 5% by weight of such gelling agents.

[0045] The compositions of the present invention can also be formulated into solid preparations (e.g., wax-based sticks, soap bars, powders, or wipes). The compositions of the present invention may be combined with solid, semi-solid, or soluble substrates (e.g., wipes, masks, pads, gloves, or strips).

[0046] Other additives The compositions of the present invention may further comprise any of a variety of additional cosmetic active agents. Examples of suitable additional active agents include skin lightening agents, tanning agents, additional anti-aging agents, tropoelastin promoters, collagen promoters, anti-acne agents, sheen adjusting agents, antimicrobial agents (e.g., anti-yeast, anti-fungal and anti-bacterial agents), anti-inflammatory agents, anti-parasitic agents, topical analgesics, sunscreens, photoprotective agents, antioxidants, keratolytic agents, detergents / surfactants, moisturizers, nutrients, vitamins, energy enhancers, antiperspirants, astringents, deodorants, hair removal agents, hair growth strengthening agents, hair growth retarding agents, stabilizers, hydration enhancers, efficacy enhancers, anti-callus agents, skin conditioning agents, anti-cellulite agents, malodor counteractants (e.g., malodor masking agents), or pH modifiers.

[0047] Examples of various suitable additional cosmetically acceptable actives include: hydroxy acids, benzoyl peroxide, D-panthenol, avobenzone (Parsol 1789), bisdisulizole disodium (Neo Heliopan AP), diethylaminohydroxybenzoylhexylbenzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone-15 (Parsol SLX), trolamine salicylate, bemotrizinol (Tinosorb S), Benzophenone 1-12, Dioxybenzone, Drometrizole Trisiloxane (Mexoryl XL), Iscotrizinol (Uvasorb HEB), Octocrylene, Oxybenzone (Eusolex 4360), Sulisobenzone, Bisoctrizole (Tinosorb UV filters such as, but not limited to, M), titanium dioxide, zinc oxide; carotenoids, free radical scavengers, spin traps, retinoids and retinoid precursors (e.g., retinol, retinoic acid, and retinyl palmitate), ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes, enzyme inhibitors, minerals, hormones (e.g., estrogen), steroids (e.g., hydrocortisone), 2-dimethylaminoethanol, copper salts (e.g., copper chloride), Cu:Gly-His-Lys, copper-containing peptides such as coenzyme Q10, amino acids (e.g., proline), vitamins, lactobionic acid, acetyl-coenzyme A, niacin, riboflavin, thiamine, ribose, electron transporters (e.g., NADH and FADH2), and other plant extracts (e.g., extracts of oat, aloe vera, feverfew, soybean, shiitake mushroom), and derivatives and mixtures thereof.

[0048] If present, any additional cosmetic active agent may be present in the composition in any suitable amount, such as from about 0.0001% to about 20% by weight of the composition, such as from about 0.001% to about 10% by weight, such as from about 0.01% to about 5% by weight, in some embodiments from 0.1% to 5%, and in other embodiments from 1% to 2%.

[0049] The compositions of the present invention may contain a cosmetically effective amount of one or more additional anti-inflammatory compounds. Examples of suitable anti-inflammatory agents include substituted resorcinols, (E)-3-(4-methylphenylsulfonyl)-2-propenenitrile (such as "Bay 11-7082" available from Sigma-Aldrich, St. Louis, Missouri), tetrahydrocurcuminoids (such as Tetrahydrocurcuminoid CG available from Sabinsa Corporation, Piscataway, NJ), extracts and materials derived from: Phellodendron amurense bark extract (PCE), unmodified soybean (Glycine max), feverfew (Tanacetum parthenium), ginger (Zingiber officinale), ginkgo biloba, madecassoside (a component of Centella asiatica extract), Cotinus coggygria, butterbur extract (Petasites hybridus), wolfberry (Lycium barbarum), milk thistle extract (Silybum marianum), honeysuckle (Lonicera japonica), Peruvian basalum (Myroxylon pereirae), sage (Salvia officinalis), cranberry extract (Vaccinium oxycoccos), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), yerba mate (Ilex paraguariensis leaf extract), white lily flower extract (Lilium candidum), olive leaf extract (Olea europaea), phloretin (apple extract), oat flour (Aveena sativa), leifenol (hops: Humulus lupulus) extract, bouglan P (Ononis spinosa), licochalcone (a component of licorice: Glycyrrhiza inflate extract), Symrelief (bisabolol and ginger extract), and combinations of two or more thereof.

[0050] In one embodiment, the anti-inflammatory agent is resorcinol. Particularly suitable substituted resorcinols include 4-hexylresorcinol and 4-octylresorcinol, especially 4-hexylresorcinol. 4-Hexylresorcinol is commercially available from Sytheon (Lincoln Park, NJ) as "SYNOVEA HR." 4-Octylresorcinol is commercially available from City Chemical LLC (West Haven, Connecticut).

[0051] "Feverfew extract" refers to an extract of the plant "Tanacetum parthenium," which may be produced according to the details set forth in U.S. Patent No. 7,537,791, entitled "PARTHENOLIDE-FREE BIOACTIVE INGREDIENTS FROM FEVERFEW (TANACETUM PARTHENIUM) AND PROCESSES FOR THEIR PRODUCTION." One particularly suitable feverfew extract is commercially available from Integrated Botanical Technologies (Ossining, NY) as approximately 20% active feverfew.

[0052] A variety of other materials may also be present in the compositions of the present invention. In one or more embodiments, the composition comprises one or more topical ingredients selected from the group consisting of surfactants, chelating agents, emollients, moisturizers, conditioners, preservatives, opacifiers, fragrances, and the like.

[0053] Emollient refers to the compound that helps maintain the soft, smooth and supple appearance of skin (for example, by remaining on the surface or stratum corneum of skin to act as lubricant).Suitable examples of emollient include those that can be found in Handbook of Cosmetic Science and Technology (edited by A. Barel, M. Paye and H. Maibach, published in 2001, Marcel Dekker, Inc. New York, NY), Chapter 35, page 399-415 (Skin Feel Agents, written by G Zocchi), for example, include but are not limited to petrolatum, hexyldecyl stearate, and vegetable, nut and vegetable oil (for example, macadamia nut oil, rice bran oil, grape seed oil, palm oil, primrose oil, hydrogenated peanut oil and avocado oil).

[0054] Moisturizing agent refers to the compound (for example, hygroscopic compound) that is intended to increase the moisture content of the top layer of skin.The example of suitable moisturizing agent includes those that can be found in Handbook of Cosmetic Science and Technology (edited by A. Barel, M. Paye and H. Maibach, published in 2001, Marcel Dekker, Inc. (New York, NY)), Chapter 35, page 399-415 (Skin Feel Agents, written by G Zocchi), for example, includes but is not limited to glycerin, sorbitol or trehalose (for example, α,α-trehalose, β,β-trehalose, α,β-trehalose), or its salt or ester (for example, trehalose-6-phosphate).

[0055] Surfactant means the surface active agent intended for cleansing or emulsifying.Suitable surfactant examples include those found in Chapter 37, pages 431-450 (Classification of surfactants, by L. Oldenhove de Guertechin) of Handbook of Cosmetic Science and Technology (edited by A. Barel, M. Paye and H. Maibach, published in 2001, Marcel Dekker, Inc. (New York, NY)), including but not limited to anionic surfactants such as sulfate, cationic surfactants such as betaine, amphoteric surfactants such as sodium cocoglycinate, and nonionic surfactants such as alkyl polyglucosides.

[0056] Examples of suitable chelating agents include those capable of protecting and preserving the compositions of the present invention. In one or more embodiments, the chelating agent is ethylenediaminetetraacetic acid ("EDTA"), more particularly tetrasodium EDTA, available commercially under the trade name "Versene 100XL" from Dow Chemical Company, Midland, Michigan.

[0057] Suitable preservatives include, for example, parabens, quaternary ammonium species, phenoxyethanol, benzoates, DMDM ​​hydantoin, organic acids, and are present in the composition in an amount of about 0 to about 1%, or about 0.05% to about 0.5%, based on the total weight of the composition.

[0058] Any type of conditioner that provides additional attributes, such as gloss, to hair is suitable for use in the present invention. Examples include, but are not limited to, volatile silicone conditioning agents having an atmospheric boiling point of less than about 220°C. Examples of suitable volatile silicones include, but are not limited to, polydimethylsiloxane, polydimethylcyclosiloxane, hexamethyldisiloxane, cyclomethicone fluids, such as the polydimethylcyclosiloxane commercially available from Dow Corning Corporation (Midland, Michigan) under the trade name "DC-345," and mixtures thereof, specifically cyclomethicone fluids. Other suitable conditioners include cationic polymers, including polyquaterniums, cationic guar, etc.

[0059] Any of a variety of commercially available pearlizing or opacifying agents are suitable for use in the composition. Examples of suitable pearlizing or opacifying agents include, but are not limited to: (a) fatty acids having from about 16 to about 22 carbon atoms, and (b) mono- or diesters of either ethylene or propylene glycol; (a) fatty acids having from about 16 to about 22 carbon atoms, (b) mono- or diesters of polyalkylene glycols of the formula HO-(JO)aH, where J is an alkylene group having from about 2 to about 3 carbon atoms and a is 2 or 3; fatty alcohols containing from about 16 to about 22 carbon atoms; fatty esters of the formula KCOOCH2L, where K and L independently contain from about 15 to about 21 carbon atoms; inorganic solids insoluble in shampoo compositions; and mixtures thereof.

[0060] Any fragrance composition suitable for use on the skin may be used in the compositions according to the present invention.

[0061] Methods and product forms The present invention further includes a method of reducing inflammation by administering to a patient in need thereof a therapeutically effective dose of a composition comprising caraway seed extract and rosemary extract, in some embodiments, the inflammation is CCR2 receptor-mediated inflammation.

[0062] The composition may be applied topically. Such topical application may be performed on any skin in need of treatment, such as the face, lips, neck, chest, back, buttocks, arms, underarms, and / or legs. The composition may also be administered to mucous membranes (i.e., into the oral cavity). In some embodiments, the extract is a polar extract of caraway seed extract and rosemary extract.

[0063] In some embodiments, the present invention is in the form of a substrate comprising the composition of the present invention.Any suitable substrate can be used.Examples of suitable substrates and substrate materials are disclosed in, for example, U.S. Patent No. 7,452,547 and U.S. Patent Application Publication No. 2009 / 0241242, the entire contents of which are incorporated herein by reference.In some embodiments, the composition is in the form of a tablet, pill, or capsule.In one or more embodiments, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid cleaning solution, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

[0064] Any suitable method can be used to apply the composition to skin in need.For example, the composition can be applied directly from the package to skin in need, can be applied by hand to skin in need, can be transferred from a substrate such as wipes or masks, or can be a combination of two or more of these.In other embodiments, the composition can be applied via a dropper, a tube, a roller, a spray and a patch, or can be added to the water that is applied to a bath or otherwise applied to skin.The composition can be applied in various ways or forms, including but not limited to leave-on cream, mask and / or serum.

[0065] While the foregoing description represents exemplary embodiments of the present invention, it will be understood that various additions, modifications, and substitutions may be made thereto without departing from the spirit and scope of the present invention. In particular, it will be apparent to those skilled in the art that the present invention can be embodied in other specific forms, structures, arrangements, and proportions, and with other elements, materials, and components, without departing from its spirit or essential characteristics. Those skilled in the art will recognize that the present invention can be used with many modifications of the structure, arrangement, proportions, materials, and components used in practicing the present invention that are particularly adapted to particular environments and operating requirements, as well as in other ways, without departing from the principles of the present invention. Therefore, the presently disclosed embodiments are to be considered in all respects as illustrative and not restrictive, and the scope of the present invention is indicated by the appended claims and is not limited to the foregoing description. It will be understood that in the claims, the term "comprises / comprising" does not exclude the presence of other elements or steps. Furthermore, reference to the singular does not exclude the plural. The terms "a", "an", "first", "second" etc. do not exclude a plurality.

[0066] All percentages, parts and percentages are based on the total weight of the compositions of the present invention unless otherwise specified. All such weights relating to listed ingredients are based on the level of the specific ingredient stated and do not include carriers or by-products that may be included in commercially available materials, unless otherwise specified. [Example]

[0067] The following test methods and materials were used in the examples.

[0068] Assay 1: CC chemokine receptor type 2 (CCR2) antagonism assay THP1 cells (American Type Culture Collection, Manassas, VA, catalog name THP-1 (ATCC® TIB-202™)) were plated in a calcium assay kit sold under the trade name Screen Quest™ Fluo-8 No Wash Calcium Assay Kit (ATC Bioquest, Sunnydale, CA, catalog name 36316) by mixing the cells at a density of 7.5E5 cells / mL in buffer 1:1 with buffer containing calcium dye reagent into 384-well polystyrene poly-d-lysine flat-bottom cell culture microplates with lids sold under the trade name CELLCOAT™ (Greiner Bio-One, Monroe, NC, catalog name 781946) and black clear bottoms at a density of 15k cells / well in 40 μL of assay buffer (HBSS / 20 mM HEPES / 0.001% Tween® 20) using a Multidrop™ (ThermoFisher) plate. The cells were plated using a Combi reagent dispenser sold by Scientific (Waltham, MA). The plates were spun down at 800 rpm for 2 minutes without inhibition. The cells were then incubated in an incubator at 37°C for 45 minutes, followed by 15 minutes at room temperature. CCR2 antagonism was assessed using the FLIPR Penta High Throughput Cellular Screening System (Molecular Devices, San Jose, CA) by measuring calcium flux induced by activation of the CCR2 receptor with its ligand, MCP1 (Peprotech, Inc., Rocky Hill, NJ, Catalog No. 300-04), at an EC80 dose of 200 nM. Using a two-addition protocol with Ex / Em490 / 525 settings, a baseline read (5 x 1 s) was taken, followed by addition of 10 μL of extract-containing buffer to the cells, and calcium flux was measured (60 x 1 s, followed by 40 x 3 s reads).Then, 10 μL of agonist (MCP1 at a final concentration of 200 nM) was added and calcium flux was measured (60 × 1 sec, followed by 40 × 3 sec lead).

[0069] For analysis, the first phase, in which the extract is added, is considered the agonist phase, and this phase determines whether the extract has any agonist effect on calcium efflux. The efflux observed in control wells treated with anhydrous DMSO (Sigma-Aldrich, St. Louis, MO) is set to 0% agonism, and the efflux observed in control wells treated with the agonist MCP1 is set to 100% agonism. In the second phase, in which an EC80 dose of MCP1 is added to all wells of the plate, the antagonism of the extract is determined. The efflux observed in wells treated with DMSO (from the first phase) is set to 0% antagonism, and the efflux observed in wells treated with the control antagonism (from the first phase) is set to 100% antagonism. The efflux in both the agonist and antagonist phases is the difference between the maximum calcium level observed in that phase and the initial baseline.

[0070] For the synergy assay, two plates were used, with two sets of synergy experiments performed on each plate, and each condition was performed in triplicate per experiment.

[0071] Assay 2: Cytokine release assay Normal human epidermal keratinocytes, P2, lot EP-BA, were procured (Sterlab, Vallauris, France) and seeded at 30,000 cells / well in reconstituted keratinocyte growth medium sold under the trade name KGM™ Gold Keratinocyte Growth medium Bulletkit™ (Lonza, Verviers, Belgium) in 96-well plates. The following day, plant extracts and heat-inactivated P. acnes (10 cells / well) procured from LGC Standards (Molsheim, France) were added. 9The medium was replaced with keratinocyte growth medium containing 1000 CFU (strain ID ATCC® 6919). The following day, conditioned medium was collected and the release of IL6, IL8, and TNFα was measured using a Bio-Plex suspension array system sold under the trade name BIOPLEX 200 (Bio-Rad Laboratories, Inc., Marnes-la-Coquette, France) along with the respective standard reference material kits, and cell viability was assessed using the MTT test. All conditions had four replicates. The extracts tested included rosemary leaf extract at final concentrations of 0.5, 5, and 25 μg / mL, caraway seed extract at a final concentration of 50 μg / mL, and a combination of these two extracts. For cytokine release assays, the effect of P. acnes alone was normalized to 100%. Relative inhibition by cotreatment was calculated using the following formula: 1 − {(observation − DMSO treatment) / (P. acnes − DMSO treatment)}.

[0072] rosemary leaf extract Rosemary leaf extract was obtained from Ungerer & Company (New Jersey, USA). Rosemary leaf extract was prepared using an organic / aqueous medium composed of water and an alcohol mixture. A typical preparation involved mixing biomass with a water / denatured ethyl alcohol (2:8) mixture at room temperature for 24 hours, filtering, and drying the filtrate under reduced pressure to obtain a solid material—the extract. The extract was suspended in anhydrous DMSO (Sigma-Aldrich) at a stock solution of 100 mg / mL. The stock solution was then serially diluted and potency tested according to the assay protocol described above.

[0073] Caraway seed extract Caraway seed (Carum carvi) extract was obtained from Ungerer & Company (New Jersey, USA). Caraway seed extract was prepared using an organic / aqueous medium composed of water and an alcohol mixture. A typical preparation involved mixing biomass with a water / ethyl alcohol (2:8, respectively) mixture at room temperature for 24 hours, filtering, and drying the filtrate under reduced pressure to obtain a solid material—the extract. The extract was suspended in anhydrous DMSO (Sigma-Aldrich) at a stock solution of 100 mg / mL. The stock solution was then serially diluted and potency tested according to the assay protocol described above.

[0074] Example 1: Inhibition of the CCR2 receptor Rosemary leaf extract and caraway seed extract were tested alone and in various combinations and evaluated for inhibition of the CCR2 receptor according to Assay 1 above. The CCR2 receptor is a chemokine receptor associated with a wide variety of inflammatory diseases / conditions. Therefore, inhibition of the receptor is associated with reduced inflammation. The results of the experiment are shown in Table 1 below.

[0075] [Table 1]

[0076] As can be seen from the table above, all tested combinations of rosemary leaf extract and caraway seed extract exhibit synergistic effects in terms of CCR2 receptor inhibition (>1-fold increase from additive levels). The synergistic effects were particularly pronounced (>1.5-fold increase from additive levels) for combinations of 5 and 10 μg / mL rosemary leaf extract with 175 μg / mL or 350 μg / mL caraway seed extract. The synergistic effects were most pronounced (2-fold increase from additive levels) for 5 μg / mL rosemary leaf extract combined with 175 μg / mL caraway seed extract.

[0077] One surprising finding from these results is the relatively small amount of extract required to demonstrate synergistic effects. For example, 175 μg / mL of caraway seed extract alone (without rosemary leaf extract) inhibited the CCR2 receptor by 10%. Doubling the amount of caraway seed extract to 350 μg / mL only resulted in 25% inhibition. However, by adding only 5 μg / mL of rosemary leaf extract, the percentage increased significantly to 28% when caraway seed extract was maintained at 175 μg / mL. This result is particularly surprising considering that 5 μg / mL of rosemary leaf extract alone (without caraway seed extract) inhibited the receptor by only 4%. This means that even at concentrations where rosemary leaf extract has very low activity alone, its mere presence significantly boosts the inhibition of caraway seed extract.

[0078] Based on the demonstrated inhibition of CCR2 receptor, it is unexpectedly found that the combination of rosemary leaf and caraway seed extract is superior (in some cases significantly superior) to either extract alone.Therefore, the synergistic combination of rosemary leaf and caraway seed extract may be effective in treating, reducing and / or ameliorating inflammation, especially when the inflammation is CCR2 receptor-mediated inflammation.

[0079] Example 2: Effect on IL-6 cytokine release Rosemary leaf extract and caraway seed extract were tested alone and in various combinations and evaluated for reduction of IL-6 cytokine release according to Assay 2 above. IL-6 is an interleukin that acts as a pro-inflammatory cytokine. Therefore, reduction of IL-6 release is associated with reduction of inflammation. The results of the experiment are shown in Table 2 below.

[0080] [Table 2]

[0081] As can be seen from the table above, all tested combinations of rosemary leaf extract and caraway seed extract show synergistic effects in terms of IL-6 reduction (>1-fold increase from additive levels). The synergistic effect was particularly pronounced for the combination of 0.5 and 5 μg / mL rosemary leaf extract with 50 μg / mL caraway seed extract.

[0082] From these results, one surprise is that at most of the concentrations tested, Carum carum seed extract and rosemary leaf extract, when tested alone, barely reduced IL-6 release or even had a negative reduction.However, when these same concentrations were combined, the reduction percentage increased significantly to over 50%.For example, with 50 μg / mL of Carum carum seed extract (without rosemary leaf extract), IL-6 receptor was reduced by only 1%.Furthermore, with 0.5 and 0.5 μg / mL of rosemary leaf extract (without Carum carum seed extract), the results actually showed a negative reduction percentage.The additive effect expected from the combination of these concentrations is still a negative effect. However, when combined, the percentage reduction increased to 58% (0.5 μg / mL rosemary leaf extract and 50 μg / mL caraway seed extract) and 63% (5 μg / mL rosemary leaf extract and 50 μg / mL caraway seed extract). This means that even at concentrations where rosemary leaf extract and caraway seed extract alone have very little (if any) activity, the presence of both extracts provides the desired IL-6 release-reducing properties. Even 25 μg / mL rosemary leaf extract, which showed a 69% reduction in IL-6 release, increased to just under 100% when combined with 50 μg / mL caraway seed extract.

[0083] Based on the demonstrated reduction in IL-6 release, it was unexpectedly found that the combination of rosemary leaf and caraway seed extract was superior (in some cases significantly superior) to either extract alone.Therefore, the synergistic combination of rosemary leaf and caraway seed extract may be effective in treating, reducing, and / or ameliorating inflammation, particularly inflammation associated with IL-6 cytokine release.

[0084] Example 3: Effect on IL-8 cytokine release Rosemary leaf extract and caraway seed extract were tested alone and in various combinations and evaluated for reduction of IL-8 cytokine release according to Assay 2 above. IL-8 is a chemoattractant cytokine associated with inflammation. Therefore, reduction of IL-8 release is associated with reduction of inflammation. The results of the experiment are shown in Table 3 below.

[0085] [Table 3]

[0086] As can be seen from the table above, all tested combinations of rosemary leaf extract and caraway seed extract show synergistic effects in terms of reducing IL-8 release (>1-fold increase from additive levels). The synergistic effect was particularly pronounced with the combination of 0.5 μg / mL rosemary leaf extract and 50 μg / mL caraway seed extract (>1.5-fold increase from additive levels).

[0087] One surprising aspect of these results is the relatively small amount of extract needed to see a synergistic effect. For example, 50 μg / mL of caraway seed extract (without rosemary leaf extract) resulted in a 37% percent reduction. When combined with just 0.5 μg / mL of rosemary leaf extract, the amount increased dramatically to 79%, even though the same concentration of rosemary leaf extract used alone only showed a modest 14% percent reduction. This means that the mere presence of rosemary leaf extract, even at a concentration that has only moderate activity alone, significantly boosts the inhibition of caraway seed extract.

[0088] Based on the demonstrated reduction in IL-8 release, it was unexpectedly found that the combination of rosemary leaf and caraway seed extract was superior (in some cases significantly superior) to either extract alone.Therefore, the synergistic combination of rosemary leaf and caraway seed extract may be effective in treating, reducing, and / or ameliorating inflammation, particularly inflammation associated with IL-8 cytokine release.

[0089] [Embodiment] (1) A composition comprising: Caraway seed extract, Rosemary extract, a pharmaceutically and / or cosmetically acceptable carrier; A composition comprising: (2) The composition of embodiment 1, further comprising a material selected from the group consisting of a surfactant, a chelating agent, an emollient, a moisturizer, a conditioner, a preservative, an opacifier, a fragrance, and combinations of two or more thereof. (3) The composition of any one of claims 1 to 2, wherein the caraway seed extract and the rosemary extract each independently comprise a polar extract. (4) The composition of any one of the preceding claims, wherein the polar extract is extracted with one or more solvents selected from the group consisting of C1-C8 alcohols, C1-C8 polyols, C1-C8 glycols, and combinations thereof. (5) The composition of any one of the preceding claims, wherein the one or more solvents are selected from the group consisting of ethanol, water, and combinations thereof.

[0090] (6) The composition of any one of embodiments 1 to 5, wherein the caraway seed extract and the rosemary extract are each independently substantially free of essential oils. (7) The composition of any one of the preceding claims, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid cleanser, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. (8) The composition of any one of embodiments 1 to 7, wherein the caraway seed extract and the rosemary extract are present in the composition at a combined concentration of about 0.1 to about 20% by weight of the total composition. (9) The composition of any one of embodiments 1 to 8, wherein the rosemary extract and the caraway seed extract are present in a weight ratio of about 1:2 to about 1:100. (10) The composition according to any one of the preceding claims, wherein the caraway seed extract is present in a concentration of about 50 to about 350 μg / mL and the rosemary extract is a rosemary leaf extract present in a concentration of about 0.5 to about 25 μg / mL.

[0091] (11) The composition according to any one of the preceding claims, wherein the caraway seed extract is present in a concentration of about 50 μg / mL and the rosemary leaf extract is present in a concentration of about 0.5 to about 5 μg / mL. (12) A composition comprising: A caraway seed extract having a concentration of about 50 to about 350 μg / mL; a rosemary leaf extract having a concentration of about 0.5 to about 25 μg / mL; a pharmaceutically and / or cosmetically acceptable carrier; Including, the caraway seed extract and the rosemary leaf extract are each independently an aqueous alcoholic extract; The composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. (13) The composition of embodiment 12, wherein the caraway seed extract is present in a concentration of about 50 μg / mL and the rosemary leaf extract is present in a concentration of about 0.5 to about 5 μg / mL. (14) The composition of any one of claims 12 to 13, wherein the caraway seed extract and the rosemary extract are present in the composition at a combined concentration of about 0.1 to about 20% by weight of the total composition. (15) The composition of any one of embodiments 12 to 14, wherein the rosemary extract and the caraway seed extract are present in a weight ratio of about 1:2 to about 1:100.

[0092] (16) The composition of any one of embodiments 12 to 15, further comprising a material selected from the group consisting of a surfactant, a chelating agent, an emollient, a moisturizer, a conditioner, a preservative, an opacifier, a fragrance, and combinations of two or more thereof.

Claims

1. 1. A composition for treating, reducing, and / or ameliorating inflammation in inflamed skin by inhibiting CCR2 receptors and / or by reducing IL-6 release and / or by reducing IL-8 release, comprising: Caraway seed extract, which is extracted in an organic / aqueous medium composed of water and an alcohol mixture; Rosemary leaf extract, which is extracted in an organic / aqueous medium composed of water and an alcohol mixture; a pharmaceutically and / or cosmetically acceptable carrier; A composition comprising:

2. The composition of claim 1 for treating, reducing, and / or ameliorating said inflammation by inhibiting the CCR2 receptor.

3. The composition of claim 1 for treating, reducing, and / or ameliorating said inflammation by reducing IL-6 release.

4. The composition of claim 1 for treating, reducing, and / or ameliorating said inflammation by reducing IL-8 release.

5. 5. The composition of any one of claims 1 to 4, further comprising a material selected from the group consisting of surfactants, chelating agents, emollients, moisturizers, conditioners, preservatives, opacifiers, fragrances, and combinations of two or more thereof.

6. The caraway seed extract and the rosemary leaf extract are １ ~C ８ Alcohol, C １ ~C ８ Polyol, C １ ~C ８ The composition according to any one of claims 1 to 5, which is an extract with a solvent comprising one or more selected from the group consisting of glycols, and combinations thereof.

7. The composition of claim 6 , wherein the solvent comprises ethanol, water, or a combination thereof.

8. 8. The composition of claim 1, wherein the caraway seed extract and the rosemary leaf extract are each independently substantially free of essential oils.

9. 9. The composition of any one of claims 1 to 8, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

10. 10. The composition of any one of claims 1 to 9, wherein the caraway seed extract and the rosemary leaf extract are present in the composition at a combined concentration of about 0.1 to about 20% by weight of the total composition.

11. 11. The composition of any one of claims 1 to 10, wherein the rosemary leaf extract and the caraway seed extract are present in a weight ratio of about 1:2 to about 1:

100.

12. 12. The composition of any one of claims 1 to 11, wherein the caraway seed extract is present in a concentration of about 50 to about 350 μg / mL and the rosemary leaf extract is present in a concentration of about 0.5 to about 25 μg / mL.

13. 13. The composition of any one of claims 1 to 12, wherein the caraway seed extract is present at a concentration of about 50 μg / mL and the rosemary leaf extract is present at a concentration of about 0.5 to about 5 μg / mL.

14. The composition according to any one of claims 1 to 13, the caraway seed extract at a concentration of about 50 to about 350 μg / mL; the rosemary leaf extract at a concentration of about 0.5 to about 25 μg / mL; The carrier; Including, the caraway seed extract and the rosemary leaf extract are each independently an aqueous alcoholic extract; The composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

15. 15. The composition of claim 14, wherein the caraway seed extract is present at a concentration of about 50 μg / mL and the rosemary leaf extract is present at a concentration of about 0.5 to about 5 μg / mL.

16. 16. The composition of claim 14 or 15, wherein the caraway seed extract and the rosemary leaf extract are present in the composition at a combined concentration of about 0.1 to about 20% by weight of the total composition.

17. 17. The composition of any one of claims 14 to 16, wherein the rosemary leaf extract and the caraway seed extract are present in a weight ratio of about 1:2 to about 1:

100.

18. 18. The composition of any one of claims 14 to 17, further comprising a material selected from the group consisting of a surfactant, a chelating agent, an emollient, a moisturizer, a conditioner, a preservative, an opacifier, a fragrance, and combinations of two or more thereof.

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