US20020006423A1 - Cosmetic skin care compositions containing pulegone - Google Patents

Cosmetic skin care compositions containing pulegone Download PDF

Info

Publication number
US20020006423A1
US20020006423A1 US09/851,282 US85128201A US2002006423A1 US 20020006423 A1 US20020006423 A1 US 20020006423A1 US 85128201 A US85128201 A US 85128201A US 2002006423 A1 US2002006423 A1 US 2002006423A1
Authority
US
United States
Prior art keywords
skin
pulegone
composition
cosmetic
applying
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
US09/851,282
Other versions
US6391324B2 (en
Inventor
Robert Carson
Krupa Patel
Sreekumar Pillai
Stewart Granger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Unilever Home and Personal Care USA
Original Assignee
Unilever Home and Personal Care USA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Unilever Home and Personal Care USA filed Critical Unilever Home and Personal Care USA
Priority to US09/851,282 priority Critical patent/US6391324B2/en
Assigned to UNILEVER HOME & PERSONAL CARE USA, DIVISION OF CONOPCO, INC. reassignment UNILEVER HOME & PERSONAL CARE USA, DIVISION OF CONOPCO, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GRANGER, STEWART PATON, CARSON, ROBERT, PILLAI, SREEKUMAR, PATEL, KRUPA
Publication of US20020006423A1 publication Critical patent/US20020006423A1/en
Application granted granted Critical
Publication of US6391324B2 publication Critical patent/US6391324B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/70Biological properties of the composition as a whole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/75Anti-irritant

Definitions

  • the present invention relates to compositions comprising pulegone and methods of improving the cosmetic appearance of the skin by topically applying such compositions to the skin.
  • the human skin consists of two major layers: the dermis, the bottom thicker layer, and the epidermis, the top thinner layer.
  • the dermis is the layer that provides strength, elasticity, and thickness to the skin. With aging, the thickness of the dermal layer is reduced, thus, partially causing the formation of wrinkles in aging skin.
  • the top layer of the skin, the epidermis provides the resilience and the barrier properties of the skin.
  • the epidermis is composed of many different cell types. Keratinocytes are the major cell type of the epidermis, consisting of nearly 75 to 80% of the total number of cells in the human epidermis.
  • the keratinocytes reside in four distinct stages of differentiation within the epidermis.
  • Epidermal differentiation is important to providing essential functions of the skin. Namely, epidermal differentiation aids the formation of a barrier layer that protects the body against the harmful substances in the environment and prevents loss of water from the body.
  • Proper formation of the barrier layer of the epidermis requires skin cells to develop correctly through space and time and demands the synchronized production of essential lipid materials such as ceramides, cholesterol and fatty acids.
  • essential lipid materials such as ceramides, cholesterol and fatty acids.
  • Such lipid materials are formed by cells in the granular layer of the epidermis and are used to compose lipid layers that in turn become the skin's essential protective barrier layer.
  • the lipid layers act as a water barrier to prevent water loss from the skin, and consequently, prevent the appearance of aged, dry, or wrinkled skin. As such, disruption of the skin's barrier layer and impairment of its functioning are associated with skin conditions such as atopic dermatitis, psoriasis, irritation and dry skin.
  • Pulegone (5-Methyl-2-(1-methylethylidene)cyclohexanone) is an essential oil which may be found in pennyroyal, a naturally occurring plant.
  • Prior art teaches the use of pulegone in applications such as pest repellants or perfumes.
  • U.S. Pat. No. 5,106,622 issued to Sherwood et al. cites the use of pennyroyal oil ( ⁇ 85% pulegone) in an insect repellent composition.
  • U.S. Pat. No. 4,193,986 issued to Trinh et al. refers to the use of oil of pennyroyal as a component of a pest repellent for pets and animals.
  • JP 08143419 refers to the use of pulegone in a bath composition for the purpose of repelling mites.
  • U.S. Pat. No. 5,466,452 issued to Whittle refers to the use of extracts of Chinese herbs, some of which contain pulegone, for the preparation of materials to be taken orally or applied topically for relief of skin problems.
  • U.S. Pat. No. 5,871,718 issued to Lucas et al. and U.S. Pat. No. 5,874,070 issued to Trinh et al. disclose odor-absorbing compositions which may be used on skin.
  • the compositions contain cyclodextrin, a molecule capable of complexing odor molecules.
  • the compositions also include a perfume, which may be pulegone. Both patents teach that perfumes in the compositions (such as pulegone) tend to complex with cyclodextrins to reduce the concentration of the perfume actually delivered to the skin.
  • the present invention relates to an oil in water emulsion of a cosmetic skin care composition
  • a cosmetic skin care composition comprising:
  • skin as used herein includes the skin on the face, neck, chest, back, arms, legs, hands, and scalp.
  • transglutaminase-1 expression and ceramide expression can reduce dry skin by improving barrier formation as well as improving cell function and metabolism. Consequently, the appearance of lines, wrinkles, and aged skin are significantly reduced. Moreover, enhanced keratinocyte differentiation and lipid production and improved glucose uptake result in improved skin color, radiance, finish, and an overall healthy and youthful appearance of the skin. It is to such improvements that the present invention is directed.
  • solubilized pulegone increases transglutaminase-1 expression (a marker for differentiation), ceramide expression, and glucose uptake.
  • Pulegone (5-Methyl-2-(1-methylethylidene)cyclohexanone) is an essential oil which is found in pennyroyal. Pulegone may be obtained from Sigma. Pulegone has the following structural formula I:
  • Pulegone must be solubilized and uncomplexed in order to deliver benefits to the skin. Particularly, solubilizing pulegone avoids evaporation of the pulegone within the composition before delivery into the skin. Moreover, if the pulegone is complexed, it is difficult to ensure that at least a minimum amount of pulegone is available for skin benefit. In a preferred embodiment, pulegone is incorporated in the inventive compositions in an amount of from 0.001% to 10%, preferably from 1% to 7%, and most preferably from 2% to 5%.
  • the inventive composition also comprises a moisturizing agent for imparting moisturizing characteristics and sensory benefits to the skin without impeding the benefits of pulegone on the skin.
  • the moisturizing agent of the present invention is selected so that the moisturizing agent does not get emulsified in the oil phase of an emulsion and therefore effectively deposits on the skin.
  • the moisturizing agent is preferably water soluble to prevent emulsification within the inventive composition prior to application onto the skin.
  • the moisturizing agent is selected from the group consisting of: propylene glycol, sorbitol, butylene, glycerin, cetostearyl alcohol, cetyl palmitate, myristyl alcohol, and palmitic alcohol, and mixtures thereof, due to commercial availability and water solubility.
  • the moisturizing agent is selected from the group consisting of butylene and propylene glycol because both act as penetration enhancers to aid in delivering the solubilized pulegone in the inventive composition to the skin.
  • the moisturizing agent is selected from an amount of from 0.5% to 50%, preferably from 5% to 15%, and most preferably from 6% to 10% of the total composition. WHY?
  • composition according to the invention also comprises a cosmetically acceptable vehicle to act as a diluent, dispersant or carrier for pulegone in the composition, so as to facilitate its distribution when the composition is applied to the skin.
  • the inventive composition may be an oil-in-water or a water-in-oil emulsion.
  • the inventive composition is an oil-in-water emulsion, wherein pulegone is dissolved in the oil phase.
  • the emulsion preferably contains at least 80 wt. % water, by weight of the vehicle.
  • the amount of water is at least 50 wt. % of the inventive composition, and most preferably from 60 to 80 wt. %, by weight of the composition.
  • the uptake may be further increased by adding an additional ingredient to the composition.
  • the ingredient is glucose or a compound that is known to break down in the skin to glucose since glucose is available for uptake without additional metabolism in the skin.
  • Compounds which break down in the skin to provide glucose include, but are not limited to, glucosamine, glucose glutamate, galactose, lactose, sucrose, and glucose phosphate esters.
  • This preferred optional ingredient is included in the inventive compositions in an amount of from 0.001% to 10%, preferably from 0.1% to 10%, most preferably from 0.1% to 5%.
  • a thickener will usually be present in amounts anywhere from 0.1% to 20% by weight, preferably from about 0.5% to 10% by weight of the composition.
  • Exemplary thickeners are cross-linked polyacrylate materials available under the trademark Carbopol from the B. F. Goodrich Company. Gums may be employed such as xanthan, carrageenan, gelatin, karaya, pectin, and locust beans gum. Under certain circumstances the thickening function may be accomplished by a material also serving as a silicone or emollient. For instance, silicone gums in excess of 10 centistokes and esters such as glycerol stearate have dual functionality.
  • Powders may be incorporated into the cosmetic composition of the invention. These powders include chalk, talc, kaolin, starch, smectite clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate and mixtures thereof.
  • the inventive compositions also preferably include sunscreens, perfumes and alpha hydroxy acids.
  • Sunscreens aid in reducing the skin's exposure to harmful UV rays.
  • Sunscreens include those materials commonly employed to block ultraviolet light.
  • Illustrative compounds are the derivatives of PABA, cinnamate and derivatives of salicylate (other than ferulyl salicylate).
  • salicylate other than ferulyl salicylate
  • octyl methoxycinnamate and 2-hydroxy-4-methoxycinnamate and 2-hydroxy4-methoxy benxophenone are commercially available under the trademarks, Parsol MCX and Bezonphenone-3, respectively.
  • the exact amount of sunscreen employed in the emulsions can vary depending upon the degree of protection desired from the sun's UV radiation.
  • adjunct minor components may also be incorporated into the cosmetic composition. These ingredients may include coloring agents, and opacifiers. Amounts of these other adjunct minor components may range anywhere from 0.001% up to 20% by weight of the composition.
  • a small quantity of the composition for example from 1 to 100 ml, is applied to exposed areas of the skin, from a suitable container or applicator and, if necessary, it is then spread over and/or rubbed into the skin using the hand or fingers or a suitable device.
  • the cosmetic skin conditioning composition of the invention can be formulated as a lotion or a cream.
  • the composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer.
  • a lotion or cream can be packaged in a bottle, a roll-ball applicator, a propellant-driven aerosol device or a container fitted with a pump suitable for finger operation.
  • the composition When the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar.
  • the invention accordingly also provides a closed container containing a cosmetically acceptable composition as herein defined.
  • the final stage of epidermal differentiation is the formation of the cornified envelope.
  • Transglutaminase the enzyme responsible for the formation of cornified envelopes, is a marker of epidermal differentiation.
  • keratinocytes isolated from neonatal foreskin by trypsin treatment, were grown in Dulbecco's Modified Eagle's Medium (DMEM, Life Technologies, Grand Island, N.Y.) with 10% fetal bovine serum in the presence of irradiated mouse fibroblasts for establishing dividing keratinocyte colonies. Cells were incubated until their second passage and stored at ⁇ 70° C. for future use. All incubations took place at 37° C. with 5% CO 2 . Frozen second passage keratinocytes were thawed and plated in T-175 flasks (Corning, Corning, N.Y.) with DMEM and grown for five days. After reaching 80% confluence, they were trypsinized and seeded into 6-well plates containing keratinocyte growth medium (KGM, Clonetics, San Diego, Calif.) with 0.15 mM calcium.
  • KGM keratinocyte growth medium
  • One set of triplicate wells was left untreated to serve as control.
  • TG-1 levels were determined by using a transglutaminase-1 (TG-1) specific monoclonal antibody as the primary antibody (BC1, Amersham, UK) and a peroxidase labeled rabbit antimouse IgG as the secondary antibody (Amersham, UK).
  • the plates were blocked at room temperature with 5% nonfat milk in Tris-buffered saline (TBS, 10 mM Tris, 150 mM NaCL, pH 8.0) for one hour followed by two hours incubation with the primary antibody (1:4000 dilution) in 1% milk/TBS at room temperature.
  • TBS Tris-buffered saline
  • a sample of the keratinocytes that were grown in the keratinocyte culture described above were placed in KGM (2 ml per well) at 0.2 million per 6-well plates and re-grown for five days until approximately 20% confluence was reached. Cells were fed and treated with pulegone as described above for the TG-1 Assay. After three days of treatment, cells were rinsed twice with PBS, then harvested by adding 3 ml of 0.1 N NaOH (Fisher) to each well and scraping with a rubber policeman. The supernatants were transferred to 16 mm ⁇ 100 mm glass test tubes with teflon-coated caps and incubated for 1 hour at 70° C.
  • PBS Phosphate Buffered Saline
  • the medium was aspirated and wells were rinsed three times with PBS before the addition of 500 ⁇ L of 0.1N NaOH/well. After 10 minutes of agitation on a shaker, a 25 ⁇ L aliquot was removed for protein analysis, and 200 ⁇ L were transferred to a scintillation vial containing 5 mL Scintillation cocktail (Scintiverse) and counting was performed on a Beckman counter. 3 H-Glucose uptake results were expressed as CPM/ ⁇ g protein.
  • Concentrations used in the examples below are of pulegone in a corn oil droplet.
  • the in vitro concentration may not be relevant to in vivo concentration because there is partitioning between the oil and the culture medium.
  • the medium concentration of the active is not the oil droplet concentration of the active.
  • the pulegone concentration in the culture medium is therefore considerably less than the concentration in the corn oil droplet.
  • Example 4 illustrates topical compositions according to the present invention.
  • the compositions can be processed in conventional manner. They are suitable for cosmetic use.
  • the compositions are suitable for application to wrinkled, rough, flaky, aged and/or UV-damaged skin and/or dry skin and post-menopausal skin to improve the appearance and the feel thereof as well as for application to healthy skin to prevent or retard deterioration thereof.

Abstract

Cosmetic skin care compositions containing pulegone. The inventive compositions improve transglutaminase-1 expression and ceramide expression, and enhance the cell uptake of glucose.

Description

    FIELD OF THE INVENTION
  • The present invention relates to compositions comprising pulegone and methods of improving the cosmetic appearance of the skin by topically applying such compositions to the skin. [0001]
  • BACKGROUND OF THE INVENTION
  • The human skin consists of two major layers: the dermis, the bottom thicker layer, and the epidermis, the top thinner layer. The dermis is the layer that provides strength, elasticity, and thickness to the skin. With aging, the thickness of the dermal layer is reduced, thus, partially causing the formation of wrinkles in aging skin. The top layer of the skin, the epidermis, provides the resilience and the barrier properties of the skin. The epidermis is composed of many different cell types. Keratinocytes are the major cell type of the epidermis, consisting of nearly 75 to 80% of the total number of cells in the human epidermis. [0002]
  • The keratinocytes reside in four distinct stages of differentiation within the epidermis. Epidermal differentiation is important to providing essential functions of the skin. Namely, epidermal differentiation aids the formation of a barrier layer that protects the body against the harmful substances in the environment and prevents loss of water from the body. Proper formation of the barrier layer of the epidermis requires skin cells to develop correctly through space and time and demands the synchronized production of essential lipid materials such as ceramides, cholesterol and fatty acids. Such lipid materials are formed by cells in the granular layer of the epidermis and are used to compose lipid layers that in turn become the skin's essential protective barrier layer. The lipid layers act as a water barrier to prevent water loss from the skin, and consequently, prevent the appearance of aged, dry, or wrinkled skin. As such, disruption of the skin's barrier layer and impairment of its functioning are associated with skin conditions such as atopic dermatitis, psoriasis, irritation and dry skin. [0003]
  • In normal skin, if the barrier function is disturbed, the epidermis re-synthesizes the deficient lipids. However, under certain conditions, a reduced capacity for re-synthesis may occur. Such is the case in aging or dry skin where skin lipid levels are in any case sub-normal and cell metabolism is impaired. Decreased uptake and utilization of glucose can lead to decreased metabolism and skin cell turnover, thereby leading to the appearance of aged, dry and flaky skin. Materials that enhance keratinocyte differentiation, increase lipid expression, or stimulate cell metabolism, may be useful in reversing such conditions to promote healthy skin. [0004]
  • Pulegone (5-Methyl-2-(1-methylethylidene)cyclohexanone) is an essential oil which may be found in pennyroyal, a naturally occurring plant. Prior art teaches the use of pulegone in applications such as pest repellants or perfumes. For example, U.S. Pat. No. 5,106,622 issued to Sherwood et al. cites the use of pennyroyal oil (˜85% pulegone) in an insect repellent composition. U.S. Pat. No. 4,193,986 issued to Trinh et al. refers to the use of oil of pennyroyal as a component of a pest repellent for pets and animals. JP 08143419 refers to the use of pulegone in a bath composition for the purpose of repelling mites. U.S. Pat. No. 5,466,452 issued to Whittle refers to the use of extracts of Chinese herbs, some of which contain pulegone, for the preparation of materials to be taken orally or applied topically for relief of skin problems. [0005]
  • U.S. Pat. No. 5,871,718 issued to Lucas et al. and U.S. Pat. No. 5,874,070 issued to Trinh et al. disclose odor-absorbing compositions which may be used on skin. The compositions contain cyclodextrin, a molecule capable of complexing odor molecules. The compositions also include a perfume, which may be pulegone. Both patents teach that perfumes in the compositions (such as pulegone) tend to complex with cyclodextrins to reduce the concentration of the perfume actually delivered to the skin. [0006]
  • The prior art cited above does not disclose cosmetic compositions that can deliver solubilized pulegone to provide the combined benefit of enhanced differentiation and enhanced expression of lipids essential to barrier function. Therefore, a need exists for cosmetic compositions that can deliver pulegone to effectively improve the cosmetic appearance of skin. [0007]
  • SUMMARY OF THE INVENTION
  • The present invention relates to an oil in water emulsion of a cosmetic skin care composition comprising: [0008]
  • (a) from about 0.001% to about 10% of solubilized pulegone of Formula I: [0009]
    Figure US20020006423A1-20020117-C00001
  • (b) a moisturizing agent; and [0010]
  • (c) a cosmetically acceptable vehicle. [0011]
  • DETAILED DESCRIPTION OF THE INVENTION
  • Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts or ratios of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about.” All amounts are by weight of the final composition, unless otherwise specified. [0012]
  • The term “skin” as used herein includes the skin on the face, neck, chest, back, arms, legs, hands, and scalp. [0013]
  • The term “solubilized” as used herein means that at least 90% of pulegone present in the final composition is solubilized. [0014]
  • An increase in transglutaminase-1 expression and ceramide expression can reduce dry skin by improving barrier formation as well as improving cell function and metabolism. Consequently, the appearance of lines, wrinkles, and aged skin are significantly reduced. Moreover, enhanced keratinocyte differentiation and lipid production and improved glucose uptake result in improved skin color, radiance, finish, and an overall healthy and youthful appearance of the skin. It is to such improvements that the present invention is directed. [0015]
  • According to the present invention, solubilized pulegone increases transglutaminase-1 expression (a marker for differentiation), ceramide expression, and glucose uptake. [0016]
  • All amounts are by weight of an oil-in-water emulsion, unless otherwise indicated. [0017]
  • Pulegone (5-Methyl-2-(1-methylethylidene)cyclohexanone) is an essential oil which is found in pennyroyal. Pulegone may be obtained from Sigma. Pulegone has the following structural formula I: [0018]
    Figure US20020006423A1-20020117-C00002
  • Pulegone must be solubilized and uncomplexed in order to deliver benefits to the skin. Particularly, solubilizing pulegone avoids evaporation of the pulegone within the composition before delivery into the skin. Moreover, if the pulegone is complexed, it is difficult to ensure that at least a minimum amount of pulegone is available for skin benefit. In a preferred embodiment, pulegone is incorporated in the inventive compositions in an amount of from 0.001% to 10%, preferably from 1% to 7%, and most preferably from 2% to 5%. [0019]
  • One fundamentally important criterion by which many topical lotions/creams must be measured is their ability to act as efficient skin moisturizers. Skin moisturizing ability is of extreme importance for topical lotions/creams in that consumers regard scaly, dry skin as unsightly and undesirable. Topical lotions that have the added benefit of enhancing skin moisture retention capabilities have a significant added benefit above and beyond the utility of their active ingredient. Thus, the inventive composition also comprises a moisturizing agent for imparting moisturizing characteristics and sensory benefits to the skin without impeding the benefits of pulegone on the skin. [0020]
  • The moisturizing agent of the present invention is selected so that the moisturizing agent does not get emulsified in the oil phase of an emulsion and therefore effectively deposits on the skin. Thus, the moisturizing agent is preferably water soluble to prevent emulsification within the inventive composition prior to application onto the skin. In the preferred embodiment, the moisturizing agent is selected from the group consisting of: propylene glycol, sorbitol, butylene, glycerin, cetostearyl alcohol, cetyl palmitate, myristyl alcohol, and palmitic alcohol, and mixtures thereof, due to commercial availability and water solubility. Most preferably, the moisturizing agent is selected from the group consisting of butylene and propylene glycol because both act as penetration enhancers to aid in delivering the solubilized pulegone in the inventive composition to the skin. [0021]
  • The moisturizing agent is selected from an amount of from 0.5% to 50%, preferably from 5% to 15%, and most preferably from 6% to 10% of the total composition. WHY?[0022]
  • The composition according to the invention also comprises a cosmetically acceptable vehicle to act as a diluent, dispersant or carrier for pulegone in the composition, so as to facilitate its distribution when the composition is applied to the skin. [0023]
  • The inventive composition may be an oil-in-water or a water-in-oil emulsion. However, to provide maximum delivery, preferably the inventive composition is an oil-in-water emulsion, wherein pulegone is dissolved in the oil phase. The emulsion preferably contains at least 80 wt. % water, by weight of the vehicle. Preferably, the amount of water is at least 50 wt. % of the inventive composition, and most preferably from 60 to 80 wt. %, by weight of the composition. [0024]
  • Optional Skin Benefit Materials and Cosmetic Adjuncts [0025]
  • According to the present invention, among the beneficial effects of pulegone is its ability to enhance glucose uptake into skin cells. While pulegone enhances the uptake of endogenous glucose, the uptake may be further increased by adding an additional ingredient to the composition. Preferably, the ingredient is glucose or a compound that is known to break down in the skin to glucose since glucose is available for uptake without additional metabolism in the skin. [0026]
  • Compounds which break down in the skin to provide glucose include, but are not limited to, glucosamine, glucose glutamate, galactose, lactose, sucrose, and glucose phosphate esters. [0027]
  • This preferred optional ingredient is included in the inventive compositions in an amount of from 0.001% to 10%, preferably from 0.1% to 10%, most preferably from 0.1% to 5%. [0028]
  • Another category of functional ingredients within the cosmetic compositions of the present invention includes thickeners. A thickener will usually be present in amounts anywhere from 0.1% to 20% by weight, preferably from about 0.5% to 10% by weight of the composition. Exemplary thickeners are cross-linked polyacrylate materials available under the trademark Carbopol from the B. F. Goodrich Company. Gums may be employed such as xanthan, carrageenan, gelatin, karaya, pectin, and locust beans gum. Under certain circumstances the thickening function may be accomplished by a material also serving as a silicone or emollient. For instance, silicone gums in excess of 10 centistokes and esters such as glycerol stearate have dual functionality. [0029]
  • Powders may be incorporated into the cosmetic composition of the invention. These powders include chalk, talc, kaolin, starch, smectite clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate and mixtures thereof. [0030]
  • The inventive compositions also preferably include sunscreens, perfumes and alpha hydroxy acids. Sunscreens aid in reducing the skin's exposure to harmful UV rays. Sunscreens include those materials commonly employed to block ultraviolet light. Illustrative compounds are the derivatives of PABA, cinnamate and derivatives of salicylate (other than ferulyl salicylate). For example, octyl methoxycinnamate and 2-hydroxy-4-methoxycinnamate and 2-hydroxy4-methoxy benxophenone are commercially available under the trademarks, Parsol MCX and Bezonphenone-3, respectively. The exact amount of sunscreen employed in the emulsions can vary depending upon the degree of protection desired from the sun's UV radiation. [0031]
  • Other adjunct minor components may also be incorporated into the cosmetic composition. These ingredients may include coloring agents, and opacifiers. Amounts of these other adjunct minor components may range anywhere from 0.001% up to 20% by weight of the composition. [0032]
  • Product Use, Form, and Packaging [0033]
  • In use, a small quantity of the composition, for example from 1 to 100 ml, is applied to exposed areas of the skin, from a suitable container or applicator and, if necessary, it is then spread over and/or rubbed into the skin using the hand or fingers or a suitable device. [0034]
  • The cosmetic skin conditioning composition of the invention can be formulated as a lotion or a cream. The composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer. For example, a lotion or cream can be packaged in a bottle, a roll-ball applicator, a propellant-driven aerosol device or a container fitted with a pump suitable for finger operation. When the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar. The invention accordingly also provides a closed container containing a cosmetically acceptable composition as herein defined. [0035]
  • The following specific examples further illustrate the invention, but the invention is not limited thereto. [0036]
  • Materials and Methods [0037]
  • The final stage of epidermal differentiation is the formation of the cornified envelope. Transglutaminase, the enzyme responsible for the formation of cornified envelopes, is a marker of epidermal differentiation. [0038]
  • Keratinocyte Culture [0039]
  • Normal human keratinocytes, isolated from neonatal foreskin by trypsin treatment, were grown in Dulbecco's Modified Eagle's Medium (DMEM, Life Technologies, Grand Island, N.Y.) with 10% fetal bovine serum in the presence of irradiated mouse fibroblasts for establishing dividing keratinocyte colonies. Cells were incubated until their second passage and stored at −70° C. for future use. All incubations took place at 37° C. with 5% CO[0040] 2. Frozen second passage keratinocytes were thawed and plated in T-175 flasks (Corning, Corning, N.Y.) with DMEM and grown for five days. After reaching 80% confluence, they were trypsinized and seeded into 6-well plates containing keratinocyte growth medium (KGM, Clonetics, San Diego, Calif.) with 0.15 mM calcium.
  • Transglutaminase (TG-1) Assay [0041]
  • A sample of the keratinocytes grown in the keratinocyte culture described above, were placed in KGM (2 ml per well) at 0.2 million cells/plate in 6-well plates and re-grown for five days until the cells reached approximately 20% confluence, since TG-1 only begins to become expressed after confluence. Two milliliters of fresh KGM were added to each well and 10 μl of corn oil containing 0, 2.5, 5 or 10% pulegone were placed on the surface of the medium each day for three days. One set of triplicate wells was left untreated to serve as control. After three days of incubation, cells were washed thoroughly with phosphate buffered saline (PBS, 10 mM sodium phosphate, 138 mM sodium chloride, 2.7 mM potassium chloride, pH 7.4) and placed at −70° C. for 2 hours. Cells were then thawed for two hours. The DNA content of cells was quantified by using the DNA-binding fluorophore, bis-benzimidazole (Hoechst 33258) and measuring the specific fluorescence of the DNA-bound fluorophore (360 nm excitation, 450 nm emission). Cellular TG-1 levels were determined by using a transglutaminase-1 (TG-1) specific monoclonal antibody as the primary antibody (BC1, Amersham, UK) and a peroxidase labeled rabbit antimouse IgG as the secondary antibody (Amersham, UK). The plates were blocked at room temperature with 5% nonfat milk in Tris-buffered saline (TBS, 10 mM Tris, 150 mM NaCL, pH 8.0) for one hour followed by two hours incubation with the primary antibody (1:4000 dilution) in 1% milk/TBS at room temperature. After rinsing the plates three times with 1% milk/TBS containing 0.05% Tween 20 (Bio-Rad, Hercules, Calif.), the plates were incubated with a 1:4000 dilution of the secondary antibody at room temperature for two hours. The plates were then rinsed three times with 1% milk/0.05% Tween 20/TBS and three times with PBS. Color was developed by incubation with o-phenylene-diamine (Sigma, St. Louis, Mo.) and hydrogen peroxide (Sigma) dissolved in a 1:1 mixture of 0.2 M dibasic sodium phosphate (Sigma) and 0.1 M citric acid at pH 5.0(Sigma). Solutions were transferred to 4 mL plastic cuvets (Fisher Scientific, Pittsburgh, Pa.) and the absorbance was read at 492 nm on an Ultraspec 3000 spectrophotometer (Pharmacia, Piscataway, N.J.) and TG-1 levels were expressed as absorbence/DNA fluoroscence. [0042]
  • Lipid Analysis [0043]
  • A sample of the keratinocytes that were grown in the keratinocyte culture described above were placed in KGM (2 ml per well) at 0.2 million per 6-well plates and re-grown for five days until approximately 20% confluence was reached. Cells were fed and treated with pulegone as described above for the TG-1 Assay. After three days of treatment, cells were rinsed twice with PBS, then harvested by adding 3 ml of 0.1 N NaOH (Fisher) to each well and scraping with a rubber policeman. The supernatants were transferred to 16 mm×100 mm glass test tubes with teflon-coated caps and incubated for 1 hour at 70° C. After cooling to room temperature, a 50 μl aliquot was removed for protein determination (Pierce BCA assay, Rockford, Ill.). To each tube 320 μl of 1 N HCl and 2.5 ml of chloroform were added and the tubes mixed well. The tubes were then placed on a tumbler and agitated for thirty minutes. The mixtures were then centrifuged for 10 minutes at 2000×g. 2 mL of chloroform were removed from the organic phase and placed in an autosampler vial. The samples were then dried evaporated under N[0044] 2, resuspended in 60 μl of chloroform:methanol 2:1 and transferred to an autosampler insert microtube which was placed inside another autosampler vial whcih was sealed. 40 μl of the sample was spotted (Camag Automatic TLC Sampler III, Wilmington, N.C.) on silica TLC plates (Whatman 4807-700) and the plates were developed in horizontal chambers (Camag) using the following solvent system: 1. 95:4.5:0.5 chloroform, methanol, acetic acid and 2. 60:40:2 hexane, ethyl ether, acetic acid. Following immersion in 10% copper sulfate in 8% phosphoric acid, plates were charred at 165° C. for 20 minutes and then read in a densitometer (Camag TLC Scanner II). The results were expressed in ng cermaides/μg protein.
  • Glucose Uptake Assay [0045]
  • A sample of the keratinocytes grown in the keratinocyte culture described above, were plated in KGM medium at either 0.5 or 1 million cells/plate in six well plates and incubated for 4 days. The medium was then aspirated, and the wells were rinsed twice with Phosphate Buffered Saline (PBS), then the plates were incubated (1 mL/well) for 24 hours. The medium was replaced with fresh KBM, 10 μl of corn oil containing pulegone at various concentrations were added and cells were allowed to incubate (for 4 hours at 37° C.) before 2 μCi of [0046] 3H 2-deoxy-glucose (Amersham, UK) were added to each well. Samples were then incubated for one hour. The medium was aspirated and wells were rinsed three times with PBS before the addition of 500 μL of 0.1N NaOH/well. After 10 minutes of agitation on a shaker, a 25 μL aliquot was removed for protein analysis, and 200 μL were transferred to a scintillation vial containing 5 mL Scintillation cocktail (Scintiverse) and counting was performed on a Beckman counter. 3H-Glucose uptake results were expressed as CPM/μg protein.
  • Concentrations used in the examples below are of pulegone in a corn oil droplet. The in vitro concentration may not be relevant to in vivo concentration because there is partitioning between the oil and the culture medium. The medium concentration of the active is not the oil droplet concentration of the active. For the pulegone to elicit its effect on the cultured cells, it must diffuse out of the corn oil into the culture medium where it is then accessible to the cells. The pulegone concentration in the culture medium is therefore considerably less than the concentration in the corn oil droplet.[0047]
  • EXAMPLE 1
  • This example investigated the effect of pulegone on transglutaminase expression in human keratinocytes, the results of which are summarized in Table 1. [0048]
    TABLE 1
    TG-1/DNA
    (Absorbance/
    Arbitrary
    Units
    of DNA ±
    Standard % of P STATISTICAL
    SAMPLE Deviation) CONTROL VALUE SIGNIFICANCE
    CONTROL 12.73 ± 1.41  100
    Pulegone 15.45 ± 2.32  121 >0.05 NO
    1%
    Pulegone 24.96 ± 4.85  196 <0.05 YES
    2.5%
    Pulegone 36.40 ± 0.89  286 <0.05 YES
    5%
  • It can be seen from the results in Table 1 that human keratinocytes exposed to pulegone at 2.5% and 5% in corn oil had increased transglutaminase-1 expression in comparison to untreated keratinocytes. [0049]
  • EXAMPLE 2
  • This example investigated the effect of pulegone on ceramides expression in human keratinocytes, the results of which are summarized in Table 2. [0050]
    TABLE 2
    CERAMIDES
    (ng/μg
    PROTEIN ± % of P STATISTICAL
    SAMPLE S.D.) CONTROL VALUE SIGNIFICANCE
    CONTROL 13.9 ± 3.60 100
    Pulegone 8.97 ± 1.17  65 >0.05 NO
    1%
    Pulegone 23.8 ± 11.0 171 >0.05 NO
    2.5%
    Pulegone 42.8 ± 6.91 308 <0.05 YES
    5%
  • It can be seen from the results in Table 2 that human keratinocytes exposed to pulegone in corn oil increased expression of ceramides in comparison to untreated keratinocytes. [0051]
  • EXAMPLE 3
  • This example investigated the effect of pulegone on glucose uptake in human keratinocytes, the results of which are shown in Table 3. [0052]
    TABLE 3
    GLUCOSE
    UPTAKE
    (cpm/μg
    PROTEIN ± % of P STATISTICAL
    SAMPLE S.D.) CONTROL VALUE SIGNIFICANCE
    CONTROL 4.83 ± 0.34 100
    Pulegone 3.71 ± 0.35  77 <0.05 YES
    1%
    Pulegone 9.14 ± 0.69 189 <0.05 YES
    5%
  • It can be seen from the results in Table 3 that human keratinocytes exposed to pulegone in corn oil significantly increased glucose uptake. [0053]
  • EXAMPLE 4
  • Example 4 illustrates topical compositions according to the present invention. The compositions can be processed in conventional manner. They are suitable for cosmetic use. In particular the compositions are suitable for application to wrinkled, rough, flaky, aged and/or UV-damaged skin and/or dry skin and post-menopausal skin to improve the appearance and the feel thereof as well as for application to healthy skin to prevent or retard deterioration thereof. [0054]
    INGREDIENT % w/w
    OIL-IN-WATER EMULSION
    Dl Water 73.40
    Carbomer 0.30
    Disodium EDTA 0.10
    Glycerin 3.00
    Polysorbate 20 2.50
    Butylene Glycol 2.00
    Methylparaben 0.30
    Triethanolamine 99% 0.30
    Pulegone 2.00
    Isopropyl Myristate 5.00
    Octyl Palmitate 3.00
    Cetyl Alcohol 1.00
    Dimethicone, 100 cst 0.50
    Beeswax 0.30
    Propylparaben 0.10
    Germall II 0.10
    Fragrance 0.10
    Total ----> 100.00
    OIL-IN-WATER EMULSION
    Dl Water 71.20
    Xanthan Gum 0.20
    Disodium EDTA 0.10
    Glycerin 5.00
    Butylene Glycol 2.00
    Methylparaben 0.30
    Pulegone 2.00
    Isopropyl Myristate 5.00
    Octyl Palmitate 3.00
    Cetyl Alcohol 1.00
    Dimethicone, 100 cst 0.50
    Steareth-2 0.40
    Steareth-21 3.00
    Propylparaben 0.10
    Germall II 0.10
    Fragrance 0.10
    Total ----> 100.00
    WATER-IN-OIL EMULSION
    Dl Water 63.30
    Disodium EDTA 0.10
    Glycerin 3.00
    Propylene Glycol 2.00
    Sodium Chloride 0.70
    Methylparaben 0.30
    Cyclomethicone 14.00
    Pulegone 2.00
    Isopropyl Myristate 5.00
    Octyl Palmitate 3.00
    Dimethicone Copolyol 2.50
    Dimethicone, 100 cst 0.50
    Beeswax 0.30
    Propylparaben 0.10
    Germall II 0.10
    Fragrance 0.10
    Total ----> 100.00
    HYDRO-GEL
    Dl Water 81.85
    Butylene Glycol 5.00
    PPG-5-Ceteth 20 5.00
    Glycerin 3.00
    Carbomer 1.20
    Triethanolamine 99% 1.20
    Pulegone 2.00
    Ascorbic acid 1.00
    Methylparaben 0.30
    Polysorbate 20 0.25
    Disodium EDTA 0.10
    Germall II 0.10
    Total ----> 100.00
    ANHYDROUS SERUM
    Cyclomethicone 72.40
    Pulegone 1.00
    Isopropyl Myristate 5.00
    Octyl Palmitate 3.00
    Polyglycerol-6 Dioleate 5.00
    Butylene Glycol 4.00
    Dimethicone, 100 cst 5.00
    Beeswax 0.30
    Propylparaben 0.20
    Fragrance 0.10
    Total ----> 100.00
    HYDRO-ALCOHOLIC GEL
    Dl Water 52.85
    Alcohol SDA40B 30.00
    Butylene Glycol 5.00
    PPG-5-Ceteth 20 5.00
    Glycerin 3.00
    Carbomer 1.20
    Triethanolamine 99% 1.20
    Pulegone 1.00
    Methylparaben 0.30
    Polysorbate 20 0.25
    Disodium EDTA 0.10
    Germall II 0.10
    Total ----> 100.00
  • It should be understood that the specific forms of the invention herein illustrated and described are intended to be representative only. Changes, including but not limited to those suggested in this specification, may be made in the illustrated embodiments without departing from the clear teachings of the disclosure. Accordingly, reference should be made to the following appended claims in determining the full scope of the invention. [0055]

Claims (9)

What is claimed is:
1. An oil in water emulsion of a cosmetic skin care composition comprising:
(a) from about 0.001% to about 10% of solubilized pulegone of Formula I:
Figure US20020006423A1-20020117-C00003
(b) a moisturizing agent; and
(c) a cosmetically acceptable vehicle.
2. The composition of claim 1 wherein the moisturizing agent is selected from the group consisting of: propylene glycol, sorbitol, butylene, glycerin, cetostearyl alcohol, cetyl palmitate, myristyl alcohol, and palmitic alcohol, and mixtures thereof.
3. The composition of claim 1 further comprising a glucose compound.
4. The composition of claim 1 further comprising a cosmetically beneficial ingredient selected from the group consisting of sunscreen, perfumes, and alpha hydroxy acids.
5. A cosmetic method of treating aged, photoaged, dry, lined or wrinkled skin, the method comprising the step of applying to the skin the composition according to claim 1.
6. A cosmetic method of improving the barrier function of the skin, the method comprising applying to the skin the composition according to claim 1.
7. A cosmetic method of improving keratinocyte differentiation, the method comprising applying to the skin the composition according to claim 1.
8. A cosmetic method of improving the lipid production by keratinocytes, the method comprising applying to the skin the composition according to claim 1.
9. A cosmetic method of improving the glucose uptake by keratinocytes, the method comprising applying to the skin the composition according to claim 1.
US09/851,282 2000-05-09 2001-05-08 Cosmetic skin care compositions containing pulegone Expired - Lifetime US6391324B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US09/851,282 US6391324B2 (en) 2000-05-09 2001-05-08 Cosmetic skin care compositions containing pulegone

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US20260200P 2000-05-09 2000-05-09
US09/851,282 US6391324B2 (en) 2000-05-09 2001-05-08 Cosmetic skin care compositions containing pulegone

Publications (2)

Publication Number Publication Date
US20020006423A1 true US20020006423A1 (en) 2002-01-17
US6391324B2 US6391324B2 (en) 2002-05-21

Family

ID=22750547

Family Applications (1)

Application Number Title Priority Date Filing Date
US09/851,282 Expired - Lifetime US6391324B2 (en) 2000-05-09 2001-05-08 Cosmetic skin care compositions containing pulegone

Country Status (8)

Country Link
US (1) US6391324B2 (en)
EP (1) EP1280510B1 (en)
AT (1) ATE421872T1 (en)
AU (1) AU7398701A (en)
CA (1) CA2407657C (en)
DE (1) DE60137569D1 (en)
MX (1) MXPA02011027A (en)
WO (1) WO2001085126A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2863887B1 (en) * 2003-12-23 2008-05-16 Jean Noel Thorel PROCESS FOR INNOFORMING A BIOCOMPATIBLE GALENIC BASE
FR2882932A1 (en) * 2005-03-14 2006-09-15 Jacqueline Martin Use of Mentha pulegium for the preparation of a composition to treat AIDS/HIV virus
EP1707212A1 (en) * 2005-03-25 2006-10-04 Jacqueline Martin- Pennyroyal for treating HIV infection

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4193986A (en) 1978-09-11 1980-03-18 Cox Nicholas D Flea composition for animals
JPH01135711A (en) * 1987-11-24 1989-05-29 Kobayashi Kose Co Ltd Hair tonic
JP2905210B2 (en) * 1989-01-23 1999-06-14 フロイント産業株式会社 Transdermal and transmucosal absorption enhancers and transdermal and transmucosal preparations
GB9104286D0 (en) 1991-02-28 1991-04-17 Phytopharm Ltd Pharmaceutical compositions for the treatment of skin disorders
US5106622A (en) 1991-03-12 1992-04-21 Karen Sherwood Repellent composition containing natural oils of citronella, cedar and wintergreen and use thereof
JPH08143419A (en) 1994-11-17 1996-06-04 Masashi Fujii Cosmetic or bathing agent capable of preventing and relieving atopic dermatitis
US5807568A (en) * 1994-12-27 1998-09-15 Mcneil-Ppc, Inc. Enhanced delivery of topical compositions containing flurbiprofen
US5879690A (en) * 1995-09-07 1999-03-09 Perricone; Nicholas V. Topical administration of catecholamines and related compounds to subcutaneous muscle tissue using percutaneous penetration enhancers
JP2000515498A (en) * 1996-07-02 2000-11-21 ノバルテイス・コンシユーマー・ヘルス・エス・アー Topical composition comprising a combination of an antihistamine compound and a terpenoid compound
US5874070A (en) 1997-06-09 1999-02-23 The Procter & Gamble Company Compositions for reducing body odor
US5871718A (en) 1997-06-09 1999-02-16 The Procter & Gamble Company Perfumed two phase compositions for reducing body odor

Also Published As

Publication number Publication date
AU7398701A (en) 2001-11-20
WO2001085126A2 (en) 2001-11-15
WO2001085126B1 (en) 2002-09-26
US6391324B2 (en) 2002-05-21
ATE421872T1 (en) 2009-02-15
WO2001085126A3 (en) 2002-06-20
EP1280510A2 (en) 2003-02-05
MXPA02011027A (en) 2003-03-10
CA2407657C (en) 2010-07-27
EP1280510B1 (en) 2009-01-28
CA2407657A1 (en) 2001-11-15
DE60137569D1 (en) 2009-03-19

Similar Documents

Publication Publication Date Title
US6270780B1 (en) Cosmetic compositions containing resveratrol
US6358517B1 (en) Cosmetic compositions containing resveratrol and retinoids
US6019992A (en) Cosmetic skin care compositions containing 4-chromanone
CZ20003112A3 (en) Cosmetic preparation
US6395286B1 (en) Cosmetic compositions containing anise extract and retinoids
US6395281B1 (en) Cosmetic skin conditioning compositions containing red yeast rice extract
US6375961B1 (en) Cosmetic skin care compositions containing cumic alcohol
US6391324B2 (en) Cosmetic skin care compositions containing pulegone
US6436416B2 (en) Cosmetic skin conditioning compositions containing high performing retinyl esters

Legal Events

Date Code Title Description
AS Assignment

Owner name: UNILEVER HOME & PERSONAL CARE USA, DIVISION OF CON

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CARSON, ROBERT;PATEL, KRUPA;PILLAI, SREEKUMAR;AND OTHERS;REEL/FRAME:012024/0703;SIGNING DATES FROM 20010430 TO 20010604

STCF Information on status: patent grant

Free format text: PATENTED CASE

FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12