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WO2020263189A1 - Phénols qui diminuent la production de lipides dans des sébocytes - Google Patents

Phénols qui diminuent la production de lipides dans des sébocytes Download PDF

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Publication number
WO2020263189A1
WO2020263189A1 PCT/SG2020/050366 SG2020050366W WO2020263189A1 WO 2020263189 A1 WO2020263189 A1 WO 2020263189A1 SG 2020050366 W SG2020050366 W SG 2020050366W WO 2020263189 A1 WO2020263189 A1 WO 2020263189A1
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Prior art keywords
skin
group
compound
composition
sebocytes
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Inventor
Jun Xi Selwyn LOW
Xinhong LIM
Maurice VAN STEENSEL
Kai Xuan Keith TAN
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Agency for Science Technology and Research Singapore
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Agency for Science Technology and Research Singapore
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/08—Antiseborrheics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents

Definitions

  • the present invention relates to phenol compounds for use in a method of decreasing lipid production in sebocytes; to compositions comprising at least such a compound; to the use of such a composition for decreasing lipid production in sebocytes; and to a cosmetic method for decreasing lipid production in sebocytes.
  • Sebum is an oily secretion of the sebaceous glands (sebocytes) of the skin that contains lipids (fat, triglycerides, and fatty acids), keratin, and cellular materials. Sebum normally constitutes a natural moisturizer for the epidermis maintaining its integrity.
  • the level of sebum production varies from person to person and depends largely on sex and age. In particular, sebum production is influenced by hormones, i.e. androgens such as testosterone, and therefore occurs most prevalently in males during adolescence.
  • hormones i.e. androgens
  • testosterone i.e. androgens
  • the complexion of the skin i.e., the color and appearance of the skin, is oily primarily due to these hormonal changes.
  • sebum production can be stimulated by physical or emotional factors, which are altered by hormones. Besides age and sex factors, sebum production is also influenced by stress, use or consumption of pharmaceuticals and drugs such as muscle stimulants and/or the presence of disease states that interfere with the autonomic nervous system such as Parkinson's, strokes, etc.
  • This overproduction of sebum may lead to aesthetic problems, such as oily/shiny skin or hair, acne-prone skin, enlarged pores, thickened skin, or poorer hold of makeup.
  • the excess sebum may act as a catalyst for acne by clogging pores leading to the formation of comedones (“blackheads” or“whiteheads”), which, when left untreated, may become inflamed and progress into acne vulgaris. Additionally, odors may be emitted as a result of excess sebum accumulation, production, or excretion.
  • the sebaceous glands are found over most of the body, although there are few on the hands or feet and none on the palms and soles. Sebaceous glands on the mid-back, forehead and chin are larger and more numerous than elsewhere (up to 400-900 glands per square centimetre). They are also numerous in the ear canal and around the genitals.
  • the sebaceous gland consists of lobes connected by ducts, which are lined with cells similar to those on the skin surface.
  • the sebum flow dynamics at the skin surface results from a multi-step process starting with sebocyte proliferation, intracellular lipid synthesis, cell lysis in the sebaceous duct, storage of sebum in the follicular reservoir, discharge through the follicular opening and spreading over the stratum corneum (Pierard, Dermatology, vol. 196, pages 126-129 (1998)). Most sebaceous glands open out into the hair follicle. Some free sebaceous glands open directly onto the skin surface. These include Meibomian glands on the eyelids, Tysons glands on the foreskin and Fordyces spots on the upper lip. Sebum is produced when the sebaceous gland disintegrates. The cells take about a week from formation to discharge.
  • the sebocyte constitutes the competent cell of the sebaceous gland.
  • the production of sebum is associated with the program of terminal differentiation of this cell.
  • the metabolic activity of the sebocyte is essentially centered around the biosynthesis of lipids (lipogenesis), and more precisely on the neosynthesis of fatty acids and the squalene.
  • cosmetic treatments for excess lipid production provide relief from the symptoms, i.e. , oiliness, enlarged pores, acne prone skin, irregular skin texture, etc., and fail to address the underlying cause.
  • the classic approach to addressing oily or shiny skin is the use of powders that provide an immediate masking effect by absorbing the excess sebum on the skin's surface.
  • various astringents and cleaning agents may be used to control sebum.
  • all of these means for lipid reduction on the skin surface are limited, producing little sustainable visible results over extended periods of time. Astringents and cleaners may actually exacerbate the condition through a rebound effect.
  • These means for combating excess and/or unwanted sebum are limited, and the need for additional approaches remains.
  • a compound capable of reducing the production of lipids constituting sebum, by the cells of the sebaceous gland would be of definite value for the treatment of oily skin.
  • an object of the present invention to provide compounds, compositions, and methods for inhibiting excess lipid accumulation and/or over production in sebocytes and/or the skin of an individual. It is a further object of the invention to improve the overall appearance of skin affected by excess lipids or lipid over-production, including treatment, reversal, and/or prevention of oily skin and/or hair, acne-prone skin, body odors, enlarged pores, etc.
  • the present invention thus relates to a compound according to Chemical Formula (I)
  • R 1 is selected from the group consisting of C2-C15 (hetero)alkenyl, C2-C15 (hetero)alkynyl, C3-C15 (hetero)cycloalkyl, and (hetero)aryl,
  • R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from the group consisting of halogen, H, OH, SH, and C1 -C10 (hetero)alkyl, preferably from the group consisting of halogen, H, OH, SH, OCHs, OCFs, CH2OH, COOH, COOCHs, and 0(C0)CH 3 ;
  • the present invention relates to a composition
  • a composition comprising at least one compound, as defined herein, and at least one pharmaceutically or cosmetically acceptable carrier.
  • the present invention relates to the use of a composition, as defined herein, for decreasing lipid production in sebocytes.
  • the present invention relates to a cosmetic method for decreasing lipid production in sebocytes or in the skin of an individual in need thereof, comprising contacting said sebocyte or skin with a lipid production-decreasing amount of at least one compound, as defined herein, or composition, as defined herein.
  • Figure 1 depicts the plate reader data showing that bakuchiol and pterostilbene reduced lipid accumulation by about 20 % and 35 %, respectively.
  • the fluorescent intensity for each compound treatment was compared against vehicle (DMSO) control treatment and EGCG (epigallocatechin gallate) as a comparative example compound.
  • Figure 2 depicts the flow cytometer data revealing that bakuchiol and pterostilbene reduced lipid accumulation by about 30 % and 15 %, respectively.
  • DMSO vehicle
  • EGCG epigallocatechin gallate
  • At least one refers to the number of chemically different molecules, i.e. to the number of different types of the referenced species, but not to the total number of molecules.
  • “One or more”, as used herein, relates to at least one and comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9 or more of the referenced species. Similarly,“at least one” means one or more, i.e. 1 , 2, 3, 4, 5, 6, 7, 8, 9 or more.
  • compositions or formulations relate to weight % relative to the total weight of the respective composition or formula, if not explicitly stated otherwise.
  • an individual in need thereof refers to an individual with a normal but noticeable and undesired skin condition, or unwanted feature, due to the excess presence or over production of lipids, e.g. hyperseborrhoea, etc., or an individual that would like to decrease the presence or production of lipids in the absence of a noticeable and undesired skin condition, i.e. as a preventative or prophylactic such as for acne or clogged pores.
  • An“amount effective” or an“effective amount” to provide a particular benefit to the skin may be correlated to a decrease in lipid production in sebocytes and that refers to the amount of phenol compound, as herein defined, required to provide a clinically measurable improvement in the particular manifestation of the lipid over-production, i.e. , an unwanted feature associated with over production of lipids, when applied or administered for a time sufficient to provide a clinically measurable improvement in the particular manifestation of lipid over-production.
  • said terms are meant to refer to an amount required to elicit the biological or medical response of a cell, tissue, animal or human that is being sought, i.e. to effectuate a decrease in lipid production in the sebocyte and/or skin.
  • reducing lipid production and“decreasing lipid production”, respectively, are used herein to mean a detectable lowering of the amount of lipids synthesized by a sebocyte exposed to a triterpenoid compound and/or composition comprising at least one such compound, as defined herein, as compared to the amount of lipids synthesized in the absence of such an inhibiting compound.
  • the terms“reduction” and“decrease”, respectively, as used herein in relation to lipids are intended to refer to the complete prevention, control of secretion, or a degree of reduction (i.e. lowering) of the production of lipids, respectively.
  • the term “lowering” may refer to about 10 % independently to about 100 % decrease in the amount of lipids synthesized.
  • the term“lowering” refers to about 15 % independently to about 95% decrease in the amount of lipids synthesized. In other embodiments, the term“lowering” refers to about 25 % independently to about 90 % decrease in the amount of lipids synthesized. In further embodiments, the term“lowering” refers to about 30% independently to about 85% decrease in the amount of lipids synthesized, and in still further embodiments, the term“lowering” refers to about 40% independently to about 80% decrease in the amount of lipids synthesized, or from 50% independently to about 75%, alternatively from 60% independently to about 70%. As used herein with respect to a range,“independently” means that any threshold may be used together with another threshold to give a suitable alternative range, e.g. 75% independently to about 90% is also considered a suitable alternative range.
  • lowering, reducing, decreasing, suppressing and inhibiting when used in relation to lipid production, are intended to be used interchangeably.
  • reduction in lipid production may be evaluated subjectively or by using assays including, but not limited to, in vitro, ex vivo, animal models, and/or clinical models known to those skilled in the art.
  • the reduction of lipid production may be established using methods known to those skilled in the art including, but not limited to, human sebocyte cultures, Rat/mouse preputial models, hamster flank/ear models and or clinical models. See K. R. Smith and D. M. Thiboutot, Thematic review series: Skin Lipids Sebaceous gland lipids: friend or foe?, Journal of Lipid Research Volume 49, 2008 271 . Further reference in this context is made to U.S. Patent Application Publication No. 20050053631 .
  • prevention as used herein, as well as related terms such as“prevent” or“preventing,” is meant to refer to provide skin not yet affected by the condition with a benefit that serves to avoid, delay, forestall, minimize, or reduce the recurrence/onset of one or more unwanted features associated with the skin condition to be prevented.
  • Such preventative benefits include, for example, delaying development and/or recurrence of the condition, or reducing the duration, severity, or intensity of one or more unwanted features associated with the condition if it eventually develops.
  • prevention is not meant to imply that all subjects in a subject population administered the compounds and/or (cosmetic) compositions described herein will never be affected by or develop the cosmetic or dermatologic conditions, damage, effect, or symptom, but rather that the subject population will exhibit a reduction in the cosmetic or dermatologic damages, effects, or symptoms.
  • many flu vaccines are not 100% effective at preventing flu in those administered the vaccine.
  • Preventing lipid over-production refers to providing not yet affected skin with a benefit that serves to avoid, delay, forestall, or minimize one or more unwanted features associated with lipid over-production, such as reducing the extent of oiliness or severity of acne, that would otherwise develop at the treated area in the absence of treatment.
  • reducing the appearance of excess lipids is meant herein to refer to any detectable reduction in skin lipids, e.g., a reduction visible to the naked eye, that occurs after contacting the skin of an individual with a phenol compound or treatment regimen comprising such a compound. As a non-limiting example, this may refer to the oiliness/shine of hyperseborrhoeic skin.
  • skin as used herein includes the skin on or in the face, mouth, neck, chest, back, arms, hands, legs, and scalp.
  • Treating lipid over-production refers to eradicating, reducing, ameliorating, or reversing one or more of the unwanted features associated with over-production of lipids.
  • Unwanted features associated with over-production of sebum include oily, shiny, acne-prone skin, oily scalp, oily hair, dandruff-prone hair, enlarged pores, or undesirable body odors associated with the over-production of lipids.
  • Treatment benefits include, without limitation, e.g., reducing the oily appearance of affected skin or hair, controlling surface oil, balancing sebum in oily-prone skin, visibly minimizing pores, reducing the incidence of acne (i.e. , clogged pores, comedones, acne vulgaris, acne lesions, cystic acne, etc.), and even reducing undesirable body odor due to accumulation of excess sebum.
  • cosmetically acceptable and “pharmaceutically acceptable”, respectively, it is meant that a particular compound or component is generally regarded as safe and nontoxic at the levels employed for cosmetic and/or pharmaceutical use.
  • pharmaceutically or cosmetically acceptable salt is meant to include salts of active compounds, which are prepared with relatively nontoxic acids or bases, depending on the particular substituent moieties found on the compounds described herein.
  • base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent.
  • pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. For more specific, non-limiting examples see, for instance, Berge et al., “Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66, 1 -19).
  • the neutral forms of the compounds may be regenerated by contacting the salt with a base or acid, respectively, and isolating the parent compound in the conventional manner.
  • the parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents.
  • Certain compounds of the disclosure can exist in unsolvated forms as well as solvated forms (“solvates”), including hydrated forms.
  • solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the disclosure.
  • Certain compounds of the disclosure may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by and are intended to be within the scope of the disclosure.
  • Certain compounds of the disclosure possess asymmetric carbon atoms (optical or chiral centers) or double bonds; the enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisometric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)-or, as (D)- or (L)- for amino acids, and individual isomers are encompassed within the scope of the disclosure.
  • the compounds of the disclosure do not include those, which are known in the art to be too unstable to synthesize and/or isolate.
  • the disclosure is meant to include compounds in racemic and optically pure forms.
  • Optically active (R)- and (S)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques.
  • the compounds described herein contain olefinic bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers.
  • tautomer refers to one of two or more structural isomers which exist in equilibrium and which are readily converted from one isomeric form to another. It will be apparent to one skilled in the art that certain compounds of the disclosure may exist in tautomeric forms, all such tautomeric forms of the compounds being within the scope of the disclosure.
  • structures depicted herein are also meant to include all stereochemical forms of the structure; i.e., the R and S configurations for each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the disclosure.
  • structures depicted herein are also meant to include compounds, which differ only in the presence of one or more isotopically enriched atoms.
  • compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13 C- or 14 C -enriched carbon are within the scope of the disclosure.
  • prodrug refers to a compound, which is in a prodrug form.
  • Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the disclosure.
  • Prodrug forms of the herein disclosed compounds are designed to improve their physicochemical properties (e.g. solubility, hydrophilicity, stability) and pharmacokinetic behavior (e.g. absorption, distribution, metabolism, excretion and toxicity).
  • Prodrugs of the herein disclosed compounds can be designed for enrichment in the target cells, tissues or organs (e.g. skin).
  • Prodrug design strategies can be carrier-linked (i.e. , they carry promoieties), can comprise spacers or can represent conjugates with biomacromolecules.
  • Prodrug forms of the herein disclosed compounds can be mono-, double-, triple- (or multiple) prodrugs as well as mono-, bi-, tri- (or multi-) functional prodrugs. They can be bioactivated by physicochemical or enzymatic mechanisms.
  • prodrugs can be converted to the compounds of the disclosure by chemical or biochemical methods in an ex vivo environment.
  • prodrugs can be slowly converted to the compounds of the disclosure when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.
  • prodrugs such as Fosphenytoin, Pivampicillin and Bacampicillin.
  • prodrug examples see J. Med. Chem. 2004, 47(10):2393- 404 and Nat. Rev. Drug Discov. 2018, 17(8):559-587.
  • alkyl by itself or as part of another substituent, means, unless otherwise stated, a straight (i.e. linear, unbranched) or branched chain, or combination thereof, which is fully saturated and can include di- and multivalent radicals, having the number of carbon atoms designated (i.e. C1 -C15 means one to fifteen carbons).
  • saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n- hexyl, n-heptyl, n-octyl, and the like.
  • heteroalkyl by itself or in combination with another term, means, unless otherwise stated, a stable linear or branched hydrocarbon chain consisting of at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized.
  • the heteroatom(s) O, N, P and S and Si may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule.
  • heteroalkyl groups include those groups that are attached to the remainder of the molecule through a heteroatom, such as— C(0)R', — C(0)NR', — NR'R", —OR', —SR', and/or— S0 2 R ⁇
  • heteroalkyl is recited, followed by recitations of specific heteroalkyl groups, such as— NR'R" or the like, it will be understood that the terms heteroalkyl and— NR'R" are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are recited to add clarity.
  • the term“heteroalkyl” should not be interpreted herein as excluding specific heteroalkyl groups, such as— NR'R” or the like.
  • cycloalkyl and “heterocycloalkyl”, by themselves or in combination with other terms, represent, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl”, respectively. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl, 1 -cyclohexenyl, 3-cyclohexenyl, and the like.
  • heterocycloalkyl examples include, but are not limited to, 1 -(1 ,2,5,6-tetrahydropyridyl), 1 -piperidinyl, 2-piperidinyl, 3-piperidinyl, 4- morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1 -piperazinyl, 2-piperazinyl, and the like.
  • halo or “halogen,” by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. According to some preferred embodiments, the halogen is fluorine.
  • aryl means, unless otherwise stated, a polyunsaturated, aromatic, hydrocarbon substituent which can be a single ring or multiple rings (such as 1 to 3 rings), which are fused together or linked covalently.
  • heteroaryl refers to aryl groups (or rings) that contain from one to four heteroatoms selected from N, O, and S, preferably selected from O and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized.
  • a heteroaryl group can be attached to the remainder of the molecule through a carbon or heteroatom.
  • Non-limiting examples of aryl and heteroaryl groups include phenyl, 1 -naphthyl, 2-naphthyl, 4-biphenyl, 1 -pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2- phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5- thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5- benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl
  • aryl refers to a polyunsaturated, aromatic, hydrocarbon substituent containing up to 10 carbon atoms.
  • heteroalkyl where a heteroalkyl, heterocycloalkyl, or heteroaryl, for instance, includes a specific number of members (e.g.“3 to 7 membered”), the term“member” refers to a carbon or heteroatom.
  • oxo as used herein means an oxygen that is double bonded to a carbon atom.
  • alkyl e.g., “alkyl”, “heteroalkyl” are meant to include both substituted and unsubstituted forms of the indicated radical, unless stated otherwise.
  • Preferred substituents for each type of radical are provided below.
  • R', R", and R"' each independently refer to hydrogen, unsubstituted C1 -C4 (hetero)alkyl, or unsubstituted C2-C4 (hetero)alkenyl.
  • each of the R groups is independently selected as are each R', R", and R'" groups when more than one of these groups is present.
  • alkyl is meant to include groups including carbon atoms bound to groups other than hydrogen groups, such as haloalkyl (e.g.,— CF 3 and— CH 2 CF3) and acyl (e.g.,— C(0)CH3,— C(0)CF3,— C(0)CH 2 0CH3, and the like).
  • haloalkyl e.g.,— CF 3 and— CH 2 CF3
  • acyl e.g.,— C(0)CH3,— C(0)CF3,— C(0)CH 2 0CH3, and the like.
  • Illustrative examples of the aforementioned substituents include, but are not limited to: halogen, preferably F, OCFs, 0C(0)CFs, C(0)0CFS (i.e.
  • substituents for the aryl and heteroaryl groups are varied and are selected from, for example: halogen,— OR',— SR', -halogen,— SiR'R"R"', — 0C(0)R', — C(0)R', — C0 2 R',— S(0)R', — S(0) 2 R', — R', unsubstituted C1 -C6 (hetero)alkyl, unsubstituted C2-C6 (hetero)alkenyl, in a number ranging from zero to the total number of open valences on the aromatic ring system; wherein, in each of the aforementioned hydrocarbon groups, including R', R", and R'", one or more hydrogen atoms may be replaced by a halogen, preferably fluorine atom; and wherein R', R", and R"' each independently refer to hydrogen, unsubstituted C1 -C4 (he
  • heteroatom or“ring heteroatom” is meant to include oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), and silicon (Si).
  • the alkenyl group can be substituted with one or more substituent groups, as described herein above. Unless stated otherwise, an alkenyl group, in the context of the present invention, may be branched or unbranched.
  • cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, and the like.
  • the cycloalkenyl group can be substituted or unsubstituted, unless stated otherwise.
  • the cycloalkenyl group can be substituted, unless stated otherwise, with one or more groups as described herein above.
  • alkynyl as used herein is a hydrocarbon group with a structural formula containing at least one carbon-carbon triple bond.
  • the alkynyl group can be unsubstituted or substituted with one or more groups as described herein above. Unless stated otherwise, an alkynyl group, in the context of the present invention, may be branched or unbranched.
  • hydrophilic group as used herein is meant to refer, in the context of the present invention, to a group, which significantly interacts with water and exhibits a significant affinity for water.
  • hydrophilic groups include a hydroxyl group (-OH), a carboxy group (-COOH), a mercapto group (-SH), a sulfonic acid group (-SO2OH), a hydroxyl- and/or carboxy-substituted alkyl group, such as CH2OH or CH2C(0)0CH3, and the like.
  • phenol compounds allow for a reduction in lipids produced by sebocytes.
  • phenol compounds represented by Chemical Formula (I), as defined herein below efficiently reduce lipid production in sebocytes.
  • the present invention relates to a compound according to Chemical Formula (I)
  • R 1 is selected from the group consisting of C2-C15 (hetero)alkenyl, C2-C15 (hetero)alkynyl, C3-C15 (hetero)cycloalkyl, and (hetero)aryl,
  • R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from the group consisting of halogen, H, OH, SH, and C1 -C10 (hetero)alkyl, preferably from the group consisting of halogen, H, OH, SH, OCHs, OCFs, CH2OH, COOH, COOCHs, and 0(C0)CH 3 ;
  • phenol compounds disclosed herein may inhibit enzymes involved in the production of sebum lipids such as fatty acid, squalene and wax esters. It is further known that retinoids, which are structurally similar to the phenol compounds of the present invention, can counteract Wingless signaling by affecting gene transcription, possibly affecting sebum production by affecting sebaceous gland differentiation.
  • substituents, if present, of the above-indicated substituent groups R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are preferably selected from the group consisting of OH, SH, OCH3, COOH, COOCHs, and 0(C0)CH 3 .
  • At least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 preferably at least two of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 , more preferably at least one of R 1 , R 3 , and R 5 , more preferably at least two of R 1 , R 3 , and R 5 denote a hydrophilic substituent group, as herein defined.
  • At least three of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 , more preferably at least three of R 1 , R 3 , and R 5 denote a hydrophilic group, as herein defined.
  • a respective hydrophilic substituent group may be selected from the group consisting of OH, SH, OCH3, OCF3, COOH, and PhOH, where applicable, more preferably from the group consisting of OH, OCH3, OCF3, and PhOH, respectively.
  • R 1 is selected from the group consisting of C2-C15 alkenyl, and aryl; and R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from the group consisting of halogen, H, OH, SH, OCFI3, OCF3, CFI2OFI, COOFI, COOCFI3, and 0(C0)CFl3, preferably from the group consisting of FI, OH, OCH3, CH2OH, COOH, COOCH3, and 0(C0)CH3.
  • substituents, if present, if the aforementioned group R 1 may be selected from the group consisting of OH, OCH3, COOH, COOCH3, and 0(C0)CH3.
  • R 2 , R 3 , R 4 , R 5 and R 6 are not all H.
  • R 4 is OH or SH, preferably OH.
  • R 4 is OH or SH, preferably SH; and R 2 , R 3 , R 5 and R 6 are each independently H or F, preferably H.
  • R 1 is selected from the group consisting of C2-C10 alkenyl, and substituted phenyl, with substituents of the aforementioned groups being independently selected from the group consisting of halogen, OH, SH, OCH3, OCF3, COOH, COOCH3, and COOCF3, preferably from the group consisting of OH, SH, OCH3, OCF3, COOH, COOCH3, and COOCF3, more preferably from the group consisting of OH, OCH3, COOH, and COOCH3.
  • R 1 is selected from the group consisting of substituted or unsubstituted, branched C4-C10 alkenyl, and substituted phenyl, with substituents of the aforementioned groups being independently selected from the group consisting of OH, SH, OCH3, and OCF3, preferably from the group consisting of OH and OCH3.
  • the compound is a compound corresponding to Chemical Formula (II) or Chemical Formula (III)
  • R 7 , R 8 and R 9 are each independently selected from the group consisting of H, F, OH, SH, OCH3, and OCF3, preferably from the group consisting of H, OH, and OCHs.
  • the compound is selected from the group consisting of bakuchiol and pterostilbene.
  • the herein disclosed and described compounds are intended for use in a method decreasing lipid production in sebocytes.
  • overproduction i.e. excess production
  • the herein described and disclosed compounds are for use in a method of treating a skin disease or disorder, and according to some embodiments, the method is the treatment of a skin disease or disorder related to increased lipid production in sebocytes.
  • said skin disease or disorder is selected from the group consisting of oily skin, shiny skin, skin having whiteheads and/or blackheads, skin having enlarged pores, and acne.
  • the amount of compound according to the present invention, i.e. according to Chemical Formula (I), for use according to the present invention, i.e. as herein disclosed, generally depends on the desired effect, and can therefore vary within a large range, this amount being within the skill of the ordinary artisan in view of this disclosure.
  • the compound can be used, for instance, in an amount in the range of about 0.0001 to 50.0 wt.-%, based on the total weight of a composition, preferably in an amount in the range of about 0.01 to 30.0 wt.-%, for instance in an amount in the range of about 0.1 to 25.0 wt.-%, based on the total weight of a composition.
  • a compound as herein defined as described i.e. a compound according to Chemical Formula (I) of the present invention
  • a plant extract comprising at least one such compound.
  • a compound according to Chemical Formula (I) of the present invention may be comprised in a composition according to the present invention, and, accordingly, in the context of the present invention, a composition comprising at least one plant extract comprising at least one compound according to Chemical Formula (I), as herein described and defined, is also envisaged and thus falling within the scope of the invention.
  • a plant extract comprising at least one compound according to Chemical Formula (I), as herein defined and described, contains this at least one compound in an amount ranging from about 0.00001 wt.-% to about 99.9 wt.-%, preferably in an amount ranging from about 0.0001 wt.-% to about 95 wt.-%, more preferably in an amount of about 0.001 wt.-% to about 95 wt.-%, particularly in an amount of about 0.01 wt.-% to about 95 wt.-%, most preferably in an amount of at least 0.1 wt.-%, such as about 0.2, 0.5, 1 .0, 1 .5, 2.0, 2.5, 3, 4, 5, 6, 7, 8, 9, 1 0, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or about 95 wt.-%, based on the total weight of the plant extract.
  • a plant extract comprising at least one compound according to Chemical Formula (I), as herein defined and described above, may be selected from the group consisting of extracts of plants belonging to the genus Ptholobium, Psoralea and Pterocarpus.
  • a plant extract comprising at least one compound according to Chemical Formula (I) of the present invention may be selected from the group consisting of Phtolobium pubescens, Psoralea corylifolia seed, Psoralea grandulosa leaves, Psoralea drupaceae, Ulmus davidiana (bark of root and stem), Otholobium pubescens, Piper longum, Aerva sangulnolenta Blume Pterocarpus marsupium (heartwood) and Vaccinium species (berries), grape leaves and vines and almonds.
  • the sebum reducing agents of the present invention i.e. the compounds according to Chemical Formula (I) defined above, may be provided in any cosmetic or pharmaceutical form normally used in the cosmetics and dermatological fields.
  • the present invention further relates to a composition
  • a composition comprising at least one compound according to Chemical Formula (I), as defined and described herein above, and at least one pharmaceutically or cosmetically acceptable carrier.
  • a composition according to the present invention is a topical composition, a cosmetic composition and/or a dermatological composition.
  • compositions may, in particular, be in the form of an aqueous, optionally gelled, solution, of a dispersion of the optionally two-phase lotion type, of an emulsion obtained by dispersion of a fatty phase (oil) in an aqueous phase (O/W) or vice versa (W/O), of a triple emulsion (W/O/W or O/W/O) or of a vesicular dispersion of the ionic and/or nonionic type.
  • a dispersion of the optionally two-phase lotion type of an emulsion obtained by dispersion of a fatty phase (oil) in an aqueous phase (O/W) or vice versa (W/O), of a triple emulsion (W/O/W or O/W/O) or of a vesicular dispersion of the ionic and/or nonionic type.
  • compositions according to the present invention may be more or less fluid and have the form of an emulsion, a cream, an ointment, a milk, a lotion, a serum, a paste, or a mousse.
  • a composition according to the present invention may optionally be applied in the form of an aerosol. It may also be provided in solid form, in particular in the form of a stick. It may be used as a care product and/or as a cosmetic product for the skin. It may also be used as a shampoo or a conditioner.
  • the compounds of Chemical Formula (I), as herein described and defined, can be formulated in various cosmetic and pharmaceutical consumer products utilizing a variety of delivery systems and carrier bases, depending on the desired form of end-use.
  • shampoos, aftershaves, sunscreens, body and hand lotions skin creams, liquid soaps, bar soaps, bath oil bars, shaving creams, conditioners, permanent waves, hair relaxers, hair bleaches, hair detangling lotion, styling gel, styling glazes, spray foams, styling creams, styling waxes, styling lotions, mousses, spray gels, pomades, shower gels, bubble baths, hair coloring preparations, conditioners, hair lighteners, coloring and non-coloring hair rinses, hair grooming aids, hair tonics, spritzes, styling waxes, band-aids, and balms may be mentioned.
  • the at least one compound according to Chemical Formula (I), as herein defined above is present in an amount of at least about 0.05 wt.-%, preferably in an amount of at least about 0.1 wt.-%, based on the total weight of the composition.
  • the at least one compound according to Chemical Formula (I), as herein defined above is present in an amount of at least about 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .5, 2.0, 2.5, 3.0,
  • the at least one compound according to Chemical Formula (I), as herein defined above is present in a composition according to the present invention an amount of about 0.05 independently to 50 wt.-%, preferably in an amount of about 0.1 independently to 40 wt.- %, more preferably in an amount of about 0.1 independently to 30 wt.-%, even more preferably in an amount of about 0.5 independently to 25 wt.-%, based on the total weight of the composition.
  • a plant extract containing one or more compounds, as disclosed and defined herein above can be present in a composition according to the present invention, for instance and without limitation, in an amount in the range of about 0.0001 independently to 20 wt.-%, and any ranges thereinbetween based on the total weight of said composition.
  • the at least one plant extract containing at least one compound according to Chemical Formula (I), as herein defined above is present in an amount of at least about 0.0001 , 0.001 , 0.01 , 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0,
  • the herein described delivery system may be in the form of a traditional water and oil emulsion, a suspension, a colloid, a micro emulsion, a clear solution, a suspension of nanoparticles, an emulsion of nanoparticles, or an anhydrous composition.
  • compositions that contain the compound of the present invention may also contain adjuvants, which are used in the cosmetics field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, pigments, odor absorbers and dyestuffs.
  • adjuvants used in the cosmetics field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, pigments, odor absorbers and dyestuffs.
  • the amounts of these various adjuvants may be those conventionally used in the field considered.
  • These adjuvants depending on their nature, can be introduced into the fatty phase, into the aqueous phase or into the lipid vesicles.
  • moisturizers may complete the effect obtained using the compounds according to the present invention.
  • a further class of useful ingredients are anti-inflammatory agents.
  • a composition according to the present invention further, i.e. in addition to the at least one compound according to Chemical Formula (I), comprises one or more excipient, i.e. one or more pharmaceutically or cosmetically acceptable carrier, which may be selected from, but is not limited to, the group consisting of water, saccharides, surface active agents, humectants, petrolatum, mineral oil, fatty alcohols, fatty ester emollients, waxes and silicone-containing waxes, silicone oil, silicone fluid, silicone surfactants, volatile hydrocarbon oils, quaternary nitrogen compounds, amine functionalized silicones, conditioning polymers, rheology modifiers, antioxidants, sunscreen active agents, long chain amines from about C10 to C22, long chain fatty amines from about C10 to C22, fatty alcohols, ethoxylated fatty alcohols and phospholipids.
  • excipient i.e. one or more pharmaceutically or cosmetically acceptable carrier, which may be selected from, but is not limited to, the group
  • composition according to the present invention further comprises at least one skin benefit agent.
  • a“skin benefit agent” is understood to mean a compound or a mixture of compounds that, upon contact with skin, lends a benefit to the skin compared to skin that was not treated with said compound or mixture of compounds.
  • This benefit can include, for example and without limitation, a moisturizing effect, a skin softening effect, U.V. protection, etc..
  • classes of skin benefit agents include moisturizing agents, antimicrobial agents, anti inflammatory agents, antioxidants, UV absorbing agents, additional anti-acne agents, skin pigmentation-inducing agents, and skin pigmentation-blocking agents, and, according to some embodiments, the composition herein described comprises at least one benefit agent selected from the above group of skin benefit agents.
  • composition as described herein may comprise at least one component selected from the group consisting of surfactants, solvents, sequestering agents, thickeners, fragrances, pH adjusters, preservatives, dyes, pigments, and opacifiers.
  • cosmetically or pharmaceutically beneficial ingredients suitable for incorporation in compositions according to the present invention may be selected from, but are not limited to, skin cleansers, cationic, anionic surfactants, non-ionic surfactants, amphoteric surfactants, and zwitterionic surfactants, skin and hair conditioning agents, vitamins, hormones, minerals, plant extracts, anti inflammatory agents, collagen and elastin synthesis boosters, UVA/UVB sunscreens, concentrates of plant extracts, emollients, moisturizers, skin protectants, humectants, silicones, skin soothing ingredients, antimicrobial agents, antifungal agents, treatment of skin infections and lesions, blood microcirculation improvement, skin redness reduction benefits, additional moisture absorbents, analgesics, skin penetration enhancers, solubilizers, moisturizers, emollients, anesthetics, colorants, perfumes, preservatives, seeds, broken seed nut shells, silica, clays, beads, luffa
  • Non-limiting examples of saccharides suitable for usage according to the present invention include nonionic or cationic saccharides such as agarose, amylopectins, amyloses, arabinans, arabinogalactans, arabinoxylans, carageenans, gum arabic, carboxymethyl guar gum, carboxymethyl(hydroxypropyl) guar gum, hydroxyethyl guar gum, carboxymethyl cellulose, cationic guar gum, cellulose ethers including methyl cellulose, chondroitin, chitins, chitosan, chitosan pyrrolidone carboxylate, chitosan glycolate chitosan lactate, cocodimonium hydroxypropyl oxyethyl cellulose, colominic acid ([poly-N acetyl-neuraminic acid]), corn starch, curdlan, dermatin sulfate, dextrans, furcellarans, dextrans, cross-linked
  • Microbial saccharides can be found in Kirk- Othmer Encyclopedia of Chemical Technology, Fourth Edition, Vol. 16, John Wiley and Sons, NY pp. 578-61 1 (1994), which is incorporated entirely by reference. Complex carbohydrates found in Kirk- Othmer Encyclopedia of Chemical Technology, Fourth Edition, Vol. 4, John Wiley and Sons, NY pp. 930-948, 1995, which is also herein incorporated by reference.
  • Non-limiting examples of surface-active agents include, without limitation, surfactants, which typically provide detersive functionality to a formulation or act simply as wetting agents.
  • Surface -active agents can generally be categorized as anionic surface-active agents, cationic surface-active agents, nonionic surface-active agents, amphoteric surface-active agents and zwitterionic surface-active agents, dispersion polymers, and combinations thereof.
  • Anionic surface-active agents useful for employment according to the present invention include, for instance, those disclosed in U.S. Pat. No. 5,573,709, incorporated herein by reference. Particular examples include alkyl and alkyl ether sulfates. Examples of alkyl ether sulfates, which may be used in compositions according to the present invention, are sodium and ammonium salts of lauryl sulfate, lauryl ether sulfate, coconut alkyl triethylene glycol ether sulfate, tallow alkyl triethylene glycol ether sulfate, tallow alkyl hexaoxyethylene sulfate, and combinations thereof.
  • Preferred alkyl ether sulfates are those comprising a mixture of individual compounds, said mixture having an average alkyl chain length of from about 12 to about 16 carbon atoms and an average degree of ethoxylation of from about 1 to about 6 moles of ethylene oxide.
  • alkyl sulfuric acid salts are also suitable classes of anionic surface-active agents.
  • alkyl sulfuric acid salts include the salts of an organic sulfuric acid reaction product of a hydrocarbon of the methane series, including iso-, neo-, and n-paraffins, having about 8 to about 24 carbon atoms, preferably about 12 to about 18 carbon atoms and a sulfonating agent, for example, sulfur trioxide or oleum, obtained according to known sulfonation methods, including bleaching and hydrolysis.
  • a sulfonating agent for example, sulfur trioxide or oleum, obtained according to known sulfonation methods, including bleaching and hydrolysis.
  • alkali metal and ammonium sulfated C12-C38 n-paraffins are preferred.
  • Additional synthetic anionic surface-active agents include the olefin sulfonates, the beta-alkyloxy alkane sulfonates, and the reaction products of fatty acids esterified with isethionic acid and neutralized with sodium hydroxide, as well as succinamates.
  • succinamates include disodium N-octadecyl sulfosuccinamate; tetrasodium N-(1 ,2-dicarboxyethyl)-N- octadecylsulfosuccinamate; diamyl ester of sodium sulfosuccinic acid; dihexyl ester of sodium sulfosuccinic acid; dioctyl esters of sodium sulfosuccinic acid, and combinations thereof.
  • Preferred anionic surface-active agents for use in compositions of the present invention include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate,
  • Non-limiting examples of suitable amphoteric surface-active agents include derivatives of aliphatic secondary and tertiary amines, in which the aliphatic substituent contains from about 8 to 18 carbon atoms and an anionic water solubilizing group e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • Representative examples include sodium 3-dodecyl-aminopropionate, sodium 3- dodecylaminopropane sulfonate, sodium lauryl sarcosinate, N-alkyltaurines such as the one prepared by reacting dodecylamine with sodium isethionate as described in U.S. Pat. No.
  • Cationic surface-active agents generally include, but are not limited to fatty quaternary ammonium compounds containing from about 8 to about 18 carbon atoms.
  • the anion of the quaternary ammonium compound can be a common ion such as chloride, ethosulfate, methosulfate, acetate, bromide, lactate, nitrate, phosphate, or tosylate and mixtures thereof.
  • the long chain alkyl groups can include additional or replaced carbon or hydrogen atoms or ether linkages.
  • substitutions on the quaternary nitrogen can be hydrogen, hydrogen, benzyl or short chain alkyl or hydroxyalkyl groups such as methyl, ethyl, hydroxymethyl or hydroxyethyl, hydroxypropyl or combinations thereof.
  • Non-limiting examples of quaternary ammonium compounds include: Behentrimonium chloride, Cocotrimonium chloride, Cethethyldimonium bromide, Dibehenyidimonium chloride, Dihydrogenated tallow benzylmonium chloride, disoyadimonium chloride, Ditallowdimonium chloride, Hydroxycetyl hydroxyethyl dimonium chloride, Hydroxyethyl Behenamidopropyl dimonium chloride, Hydroxyethyl Cetyidimonium chloride, Hydroxyethyl tallowdimonium chloride, myristalkonium chloride, PEG-2 Oleamonium chloride, PEG-5 Stearmonium chloride, PEG-15 cocoyl quaternium 4, PEG-2 stearalkonium 4, lauryltrimonium chloride; Quaternium-16; Quaternium-18, lauralkonium chloride, olealkmonium chloride, cetylpyr
  • compositions according to the present inventions are long chain (from about C10 to C22) fatty amines and their derivatives. Specific examples include dipalmitylamine, lauramidopropyidimethylamine, and stearamidopropyl dimethylamine.
  • Fatty alcohols typically monohydric alcohols
  • ethoxylated fatty alcohols and di-tail phospholipids are also suitable and can be used to stabilize emulsion or dispersion forms of the herein described compositions. They also provide a cosmetically acceptable viscosity.
  • Selection of the fatty alcohol is not critical, although those alcohols characterized as having fatty chains of C10 to C32, preferably C14 to C22, which are substantially saturated alkanols will generally be employed.
  • Non-limiting examples include stearyl alcohol, cetyl alcohol, cetostearyl alcohol, myristyl alcohol, behenyl alcohol, arachidic alcohol, isostearyl alcohol, isocetyl alcohol, and combinations thereof.
  • Cetyl alcohol is preferred and may be used alone or in combination with other fatty alcohols, preferably with stearyl alcohol.
  • the fatty alcohol is preferably included in the formulations of this invention at a concentration within the range from about 1 to about 8 weight percent, more preferably about 2 to about 6 weight percent.
  • the fatty alcohols may also be ethoxylated. Specific examples include cetereth-20, steareth-20, steareth- 21 , and mixtures thereof.
  • Phospholipids such as phosphatidylserine and phosphatidylcholine, and mixtures thereof may also be included.
  • the fatty alcohol component is included in the formulations at a concentration of about 1 to about 10 weight percent, more preferably about 2 to about 7 weight percent.
  • Non-limiting of nonionic surface-active agents include those broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound, which may be aliphatic or alkyl aromatic in nature.
  • nonionic surface -active agents are: the long chain alkanolamides; the polyethylene oxide condensates of alkyl phenols; the condensation product of aliphatic alcohols having from about 8 to about 18 carbon atoms, in either straight chain or branched chain configuration, with ethylene oxide; the long chain tertiary amine oxides; the long chain tertiary phosphine oxides; the long chain dialkyl sulfoxides containing one short chain alkyl or hydroxy alkyl radical of from about 1 to about 3 carbon atoms; and the alkyl polysaccharide (APS) surfactants such as the alkyl polyglycosides; the polyethylene glycol (PEG) glyceryl fatty esters.
  • APS alkyl polysaccharide
  • Non-limiting examples of zwitterionic surface-active agents include betaines.
  • betaines useful for employment according to the present invention include the high alkyl betaines, such as coco dimethyl carboxymethyl betaine, cocoamidopropyl betaine, cocobetaine, lauryl amidopropyl betaine, oleyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyl) carboxymethyl betaine, stearyl bis-(2-hydroxypropyl) carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, and lauryl bis-(2-hydroxypropyl)alpha-carboxyethyl betaine.
  • the sulfobetaines may be represented by coco dimethyl sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl) sulfopropyl betaine and the like; amidobetaines and amidosulfobetaines are also useful.
  • the anionic, cationic, nonionic, amphoteric or zwitterionic surface-active agents may typically be used in an amount from about 0.1 to 50 wt.-%, preferably from about 0.5 to about 40 wt.-%, more preferably from about 1 to about 20 wt.-%, based on the total weight of the respective composition.
  • Humectants act as hygroscopic agents, increasing the amount of water absorbed, held and retained.
  • Suitable humectants for the formulations of this invention include, but are not limited to: acetamide MEA, ammonium lactate, chitosan and its derivatives, colloidal oatmeal, galactoarabinan, glucose glutamate, glerecyth-7, glygeryth-12, glycereth-26, glyceryth-31 , glycerin, lactamide MEA, lactamide DEA, lactic acid, methyl gluceth-10, methyl gluceth-20, panthenol, propylene glycol, sorbitol, polyethylene glycol, 1 ,3-butanediol, 1 ,2,6-hexanetriol, hydrogenated starch hydrolysate, inositol, mannitol, PEG-5 pentaerythritol ether, polyglyceryl
  • Glycerin is a particularly preferred humectant. If present, the humectant is present in the composition at concentrations of from about 0.5 independently to about 40 wt.-%, preferably from about 0.5 independently to about 20 wt.-%, and more preferably from about 0.5 independently to about 12 wt.-%, based on the total weight of the respective composition.
  • Petrolatum or mineral oil components suitable for employment according to the present invention will generally be USP or NF grade.
  • the petrolatum may be white or yellow.
  • the viscosity or consistency grade of petrolatum is not narrowly critical.
  • Petrolatum can be partially replaced with mixtures of hydrocarbon materials, which can be formulated to resemble petrolatum in appearance and consistency. For example, mixtures of petrolatum or mineral oil with different waxes and the like may be combined.
  • Preferred waxes include bayberry wax, candelilla wax, ceresin, jojoba butter, lanolin wax, montan wax, ozokerite, polyglyceryl-3-beeswax, polyglyceryl-6-pentastearate, microcrystalline wax, paraffin wax, isoparaffin, vaseline solid paraffin, squalene, oligomer olefins, beeswax, synthetic candelilla wax, synthetic carnauba, synthetic beeswax and the like may be blended together. Alkylmethyl siloxanes with varying degrees of substitution can be used to increase water retained by the skin.
  • Siloxanes such as stearyl dimethicone, known as 2503 Wax, C30-45 alkyl methicone, known as AMS-C30 wax, and stearoxytrimethylsilane (and) stearyl alcohol, known as 580 Wax, each available from Dow Corning, Midland, Mich., USA. Additional alkyl and phenyl silicones may be employed to enhance moisturizing properties. Resins such as dimethicone (and) trimethylsiloxysilicate or Cyclomethicone (and) Trimethylsiloxysilicate fluid, may be utilized to enhance film formation of skin care products.
  • the petrolatum, wax or hydrocarbon or oil component is included in the formulations at a concentration of about 1 independently to about 20 wt.- %, more preferably about 1 independently to about 12 wt.-%, based on the total weight of the composition.
  • the silicone resins can be included from about 0.1 independently to about 10.0 wt.-%, based on the total weight of the respective composition.
  • Emollients are defined as agents that help maintain the soft, smooth, and pliable appearance of skin. Emollients function by their ability to remain on the skin surface or in the stratum corneum.
  • Composition according to the present invention may include, for instance and without limitation, fatty ester emollients, which are listed in the International Cosmetic Ingredient Dictionary, Eighth Edition, 2000, p. 1768 to 1773.
  • Suitable fatty esters for use in the formulation of this invention include isopropyl myristate, isopropyl palmitate, caprylic/capric triglycerides, cetyl lactate, cetyl palmitate, hydrogenated castor oil, glyceryl esters, hydroxycetyl isostearate, hydroxy cetyl phosphate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, PPG-5-Ceteth-20, 2- ethylhexyl isononoate, 2-ethylhexyl stearate, C12 to C16 fatty alcohol lactate, isopropyl lanolate, 2- ethyl-hexyl salicylate, and mixtures thereof.
  • the presently preferred fatty esters are isopropyl myristate, isopropyl palmitate, PPG-5-Ceteth-20, and caprylic/capric triglycerides.
  • the fatty ester emollient is preferably included in the formulations of this invention at a concentration of about 1 to about 8 wt.-%, more preferably about 2 to about 5 wt.-%, based on the total weight of the respective formulation.
  • Further suitable for employment in the context of the present invention are silicone compounds.
  • the viscosity of the silicone component is from about 0.5 to about 12,500 cps.
  • suitable materials are dimethylpolysiloxane, diethylpolysiloxane, dimethylpolysiloxane- diphenylpolysiloxane, cyclomethicone, trimethylpolysiloxane, diphenylpolysiloxane, and mixtures thereof.
  • Dimethicone a dimethylpolysiloxane endblocked with trimethyl units, is one preferred example. Dimethicone having a viscosity between 50 and 1 ,000 cps is particularly preferred.
  • the silicone oils are preferably included in the formulations of this invention at a concentration of 0.1 to 5 wt.-%, more preferably 1 to 2 wt.-%, based on the total weight of the respective formulation.
  • a composition, as herein described, may further contain volatile and non-volatile silicone oils or fluids.
  • the silicone compounds can be either linear or cyclic polydimethylsiloxanes with a viscosity from about 0.5 to about 100 centistokes. The most preferred linear polydimethylsiloxane compounds have a range from about 0.5 to about 50 centistokes.
  • One example of a linear, low molecular weight, volatile polydimethylsiloxane is octamethyltrisiloxane 200 fluid having a viscosity of about 1 centistoke.
  • the silicone oils are preferably included in the formulations of this invention at a concentration of 0.1 to 30 wt.-%, more preferably 1 to 20 wt.-%, based on the total weight of the respective formulation.
  • cyclic volatile siloxanes may be selected from polydimethyl cyclosiloxanes having an average repeat unit of 4 to 6, and a viscosity from about 2.0 to about 7.0 centistokes, and mixtures thereof.
  • Preferred cyclomethicones are available from Dow Corning, Midland, Mich., and from General Electric, Waterford, N.Y., USA.
  • the silicone oils may be included in the formulations of this invention at a concentration of 0.1 to 30 wt.-%, more preferably 1 to 20 wt.-%, based on the respective total weight of a formulation according to the present invention.
  • Silicone surfactants or emulsifiers with polyoxyethylene or polyoxypropylene side chains may also be used in compositions of the present invention.
  • Preferred examples include dimethicone copolyols and 5225C Formulation Aids, available from Dow Corning, Midland, Mich., USA and Silicone SF-1528, available from General Electric, Waterford, N.Y., USA.
  • the side chains may also include alkyl groups such as lauryl or cetyl. Preferred are lauryl methicone copolyol. 5200 Formulation Aid, and cetyl dimethicone copolyol, known as Abil EM-90, available from Goldschmidt Chemical Corporation, Flopewell, Va.
  • lauryl dimethicone known as Belsil LDM 3107 VP, available from Wacker-Chemie, MOnchen, Germany.
  • the silicone surfactants are preferably included in the formulations of this invention at a concentration of 0.1 to 30 weight percent, more preferably 1 to 15 weight percent.
  • Amine functional silicones and emulsions may be utilized in the present invention. Preferred examples include Dow Corning 8220, Dow Corning 939, Dow Corning 949, Dow Corning 2- 8194, all available from Dow Corning, Midland, Mich., USA.
  • Silicone SM 253 available from General Electric, Waterford, N.Y., USA.
  • the amine functional silicones may be included in the formulations of this invention at concentrations in the range of 0.1 to 5 wt.-%, more preferably in the range of 0.1 to 2.0 wt.-%.
  • volatile hydrocarbon oils comprising from about C6 to C22 atoms.
  • a non-limiting example of preferred volatile hydrocarbons is an aliphatic hydrocarbon having a chain length from about C6 to C16 carbon atoms.
  • An example of such a compound is isohexadecane, sold under the tradename Permethyl 101 A, available from Presperse, South Plainfield, N.J., USA.
  • Another example of a preferred volatile hydrocarbon is C12 to C14 isoparaffin, marketed under the tradename Isopar M, available from Exxon, Baytown, Tex., USA.
  • the volatile hydrocarbons are preferably included in the formulations of this invention at a concentration in the range of about 0.1 independently to 30 wt.-%, more preferably about 1 independently to 20 wt.-%.
  • compositions may further contain cationic and ampholytic conditioning polymers.
  • cationic and ampholytic conditioning polymers include, but are not limited to, those listed by the International Cosmetic Ingredient Dictionary published by the Cosmetic, Toiletry, and Fragrance Association (CTFA), 1 1 10 17 Street, N.W., Suite 300, Washington, D.C. 20036.
  • CTFA Cosmetic, Toiletry, and Fragrance Association
  • General, non-limiting examples include quaternary derivatives of cellulose ethers, quaternary derivatives of guar, homopolymers and copolymers of DADMAC, homopolymers and copolymers of MAPTAC and quaternary derivatives of starches.
  • CTFA designation examples include, but are not limited to Polyquaternium-10, Guar hydroxypropyltrimonium chloride, Starch hydroxypropyltrimonium chloride, Polyquaternium-4, Polyquaternium-5, Polyquaternium-6, Polyquaternium-7, Polyquaternium-14, Polyquaternium-15, Polyquaternium-22, Polyquaternium-24, Polyquaternium-28, Polyquaternium-32, Polyquaternium-33, Polyquaternium-36, Polyquaternium-37, Polyquaternium-39, Polyquaternium-45, Polyquaternium-47 and polymethacrylamidopropyltrimonium chloride, and mixtures thereof.
  • the conditioning polymers are preferably included in the herein described compositions at a concentration in the range of about 0.1 independently to 10 wt.-%, preferably about 0.2 independently to 6 wt.-% and most preferably about 0.2 independently to 5 wt.-%.
  • rheological modifiers include, but are not limited to, high molecular weight crosslinked homopolymers of acrylic acid, and Acrylates/C 10-30 Alkyl Acrylate Crosspolymer, such as the Carbopol and Pemulen series, both available from B. F.
  • anionic acrylate polymers such as Salcare and cationic acrylate polymers such as Salcare SC96, available from Ciba Specialties, High Point, N.C., USA; Acrylamidopropylttrimonium chloride/acrylamide; Flydroxyethyl methacrylates polymers, Steareth-10 Allyl Ether/ Acrylate Copolymer; Acrylates/Beheneth-25 Metacrylate Copolymer, known as Aculyn, available from International Specialties, Wayne, N.J., USA; Glyceryl Polymethacrylate, Acrylates/Steareth-20 Methacrylate Copolymer; bentonite; gums such as alginates, carageenans, gum acacia, gum arabic, gum ghatti, gum karaya, gum tragacanth, guar gum; guar hydroxypropyltrimonium chloride, xanthan gum or gellan gum; cellulose derivatives such as Salcare SC96, available from Cib
  • the rheology modifiers are preferably included in the composition according to the present invention at a concentration in the range of about 0.01 independently to 12 wt.-%, preferably about 0.05 independently to 10 wt.-%, and most preferably about 0.1 independently to 6 wt.-%.
  • a composition, as herein disclosed and described, may further include one or more antioxidants, which may be selected from, but are not limited to the group consisting of ascorbic acid, BHT, BHA, erythorbic acid, bisulfite, thioglycolate, tocopherol, sodium metabisulfite, vitamin E acetate, and ascorbyl palmitate.
  • the antioxidants may be present in the herein described compositions at a concentration in the range of about 0.01 independently to 5 wt.-%, preferably about 0.1 independently to 3 wt.-%, and most preferably about 0.2 independently to 2 wt.-%, based on the total weight of a respective composition.
  • sunscreen active agents suitable for incorporation in compositions as herein described include, but are not limited to octyl methoxycinnamate (ethylhexyl p-methoxycinnamate), octyl salicylate oxybenzone (benzophenone-3), benzophenone-4, menthyl anthranilate, dioxybenzone, aminobenzoic acid, amyl dimethyl PABA, diethanolamine p-methoxy cinnamate, ethyl 4-bis (hydroxypropyl) aminobenzoate, 2-ethylhexy 1 -2-cyano-3,3-diphenylacrylate, homomenthyl salicylate, glyceryl aminobenzoate, dihydroxyacetone, octyl dimethyl PABA, 2-phenylbenzimidazole-5-sulfonic acid, triethanolamine salicylate, zinc oxide, titanium oxide, and mixtures thereof.
  • octyl methoxycinnamate e
  • the amount of sunscreen used in a composition according to the present invention will vary depending on the specific UV absorption wavelength(s) of the specific sunscreen active(s) used and may, for instance, be in the range of about 0.1 independently to 10 wt.-%, preferably about 2 independently to 8 wt.-%.
  • Non-limiting example of preservatives useful in the context of the present invention include, but are not limited to 1 ,2-dibromo-2,4-dicyano butane (Methyldibromo Glutaronitrile, known as MERGUARD.
  • Non-limiting examples of further ingredients include, but are not limited to buffering agents, fragrance ingredients, chelating agents, color additives or dyestuffs which can serve to color the composition itself or keratin, sequestering agents, softeners, foam synergistic agents, foam stabilizers, sun filters and peptizing agents.
  • pigments such titanium dioxide, zinc oxide, talc, calcium carbonate or kaolin
  • treated pigments are more effective as sunscreen actives and may further be used in color cosmetics such as make up and mascara.
  • compositions can be presented in various forms. Examples of such forms include, but are not limited a solution, liquid, cream, emulsion, dispersion, gel, thickening lotion.
  • compositions according to the present invention may contain water and also any cosmetically and/or pharmaceutically acceptable solvent.
  • acceptable solvents include, but are not limited to monoalcohols, such as alkanols having 1 to 8 carbon atoms (like ethanol, isopropanol, benzyl alcohol and phenylethyl alcohol) polyalcohols, such as alkylene glycols (like glycerine, ethylene glycol and propylene glycol) and glycol ethers, such as mono-, di- and tri-ethylene glycol monoalkyl ethers, for example ethylene glycol monomethyl ether and diethylene glycol monomethyl ether, used singly or in a mixture.
  • These solvents can be present in proportions of up to as much as 70 wt.-%, for example from about 0.1 to 70 wt.-%, based on the total weight of the respective composition.
  • compositions as herein described can also be packaged as an aerosol, in which case it can be applied either in the form of an aerosol spray or in the form of an aerosol foam.
  • propellant gas for these aerosols in particular but without limitation, dimethyl ether, carbon dioxide, nitrogen, nitrous oxide, air and volatile hydrocarbons, such as butane, isobutane, and propane, may be mentioned.
  • electrolytes such as aluminum chlorohydrate, alkali metal salts, e.g., sodium, potassium or lithium salts, these salts preferably being halides, such as the chloride or bromide, and the sulfate, or salts with organic acids, such as the acetates or lactates, and also alkaline earth metal salts, preferably the carbonates, silicates, nitrates, acetates, gluconates, pantothenates and lactates of calcium, magnesium and/or strontium, and combinations thereof.
  • alkali metal salts e.g., sodium, potassium or lithium salts
  • these salts preferably being halides, such as the chloride or bromide, and the sulfate, or salts with organic acids, such as the acetates or lactates, and also alkaline earth metal salts, preferably the carbonates, silicates, nitrates, acetates, gluconates, pantothenates and lactates of
  • compositions for treating skin that contain at least one compound according to Chemical Formula (I), as herein disclosed and described, and at least one pharmaceutically or cosmetically acceptable carrier include leave-on or rinse-off skin care products such as lotions, hand/body creams, shaving gels or shaving creams, body washes, sunscreens, liquid soaps, deodorants, antiperspirants, suntan lotions, after sun gels, bubble baths, hand or mechanical dishwashing compositions, and the like. Any components of the herein described compositions must in general be safe for application to the human skin and must be compatible with the other components of the formulation. Selection of these components is generally within the skill of the art.
  • the skin care compositions may also contain other conventional additives employed in cosmetic skin care formulations. Such additives include aesthetic enhancers, fragrance oils, dyes and medicaments such as menthol and the like.
  • a composition as herein described and defined is a skin cleanser, toner, serum, lotion, cream, emulsion, gel, make-up composition (foundation, make-up, powder), skin mask, hair mask, shampoo, or conditioner.
  • the skin care compositions that contain sebum reducing agents of the present invention may be prepared as oil-in-water, water-in-oil emulsions, triple emulsions, or dispersions.
  • Preferred oil-in-water emulsions are prepared by first forming an aqueous mixture of the water-soluble components, e.g. unsaturated quaternary ammonium compounds, humectants, water-soluble preservatives, followed by adding water-insoluble components.
  • the water-insoluble components include the emulsifier, water-insoluble preservatives, petrolatum or mineral oil component, fatty alcohol component, fatty ester emollient, and silicone oil component.
  • the input of mixing energy will be high and will be maintained for a time sufficient to form a water-in-oil emulsion having a smooth appearance (indicating the presence of relatively small micelles in the emulsion).
  • Preferred dispersions are generally prepared by forming an aqueous mixture of the water-soluble components, followed by addition of thickener with suspension power for water-insoluble materials.
  • compositions that contain at least one lipid production-decreasing compound, i.e. at least one compound according to Chemical Formula (I), as herein defined above, for treating hair include bath preparations such as bubble baths, soaps, and oils, shampoos, conditioners, hair bleaches, hair coloring preparations, temporary and permanent hair colors, color conditioners, hair lighteners, coloring and non-coloring hair rinses, hair tints, hair wave sets, permanent waves, curling, hair straighteners, hair grooming aids, hair tonics, hair dressings and oxidative products.
  • the compounds of the present invention may also be utilized in styling type leave-in products such as gels, mousses, spritzes, styling creams, styling waxes, pomades, balms, and the like.
  • compositions according to the present invention generally contain anionic, cationic, nonionic, zwitterionic and/or amphoteric surface-active agents typically in an amount from about 3 independently to about 50 wt.-%, preferably from about 3 independently to about 20 wt.-%, and the pH of such compositions is generally in the range from about 3 independently to about 10.
  • Rinsing lotions according to the present invention to be applied mainly before or after shampooing, are typically aqueous or aqueous-alcoholic solutions, emulsions, thickened lotions or gels. If the compositions are presented in the form of an emulsion, they can be nonionic, anionic or cationic.
  • the nonionic emulsions consist mainly of a mixture of oil and/or a fatty alcohol with a polyoxyethyleneated alcohol, such as polyoxyethyleneated stearyl or cetyl/stearyl alcohol, and cationic surface-active agents can be added to these compositions.
  • the anionic emulsions are formed essentially from soap.
  • compositions according to the present invention are presented in the form of a thickened lotion or a gel, they contain thickeners in the presence or absence of a solvent.
  • Thickeners which can be used, may be selected from resins, Carbopol-type acrylic acid thickeners available from B.F. Goodrich; xanthan gums; sodium alginates; gum arabic; cellulose derivatives and poly-(ethylene oxide) based thickeners. It is also possible to achieve thickening by means of a mixture of polyethylene glycol stearate or distearate, or by means of a mixture of a phosphoric acid ester and an amide.
  • the concentration of thickener is generally in the range of about 0.05 to 15 wt.-%, based on the total weight of the respective composition.
  • compositions of the present invention may also contain one or more hair fixative polymers.
  • hair fixative polymers may be present in an amount of about 0.25 to about 10 wt.-%, based on the total weight of the respective composition.
  • hair fixative resins may be selected from the group consisting of acrylamide copolymer, acrylamide/sodium acrylate copolymer, acrylate/ammonium methacrylate copolymer, an acrylate copolymer, an acrylic/acrylate copolymer, adipic acid/dimethylaminohydroxypropyl diethylenetriamine copolymer, adipic acid/epoxypropyl diethylenetriamine copolymer, allyl stearate/VA copolymer, aminoethylacrylate phosphate/acrylate copolymer, an ammonium acrylate copolymer, an ammonium vinyl acetate/acrylate copolymer, an AMP acrylate/diacetoneacrylamide copolymer, an AMPD acrylate/diacetoneacrylamide copolymer, butyl ester of ethylene/maleic anhydride copolymer, butyl ester of PVM/MA copolymer, calcium/sol,
  • compositions according to the present invention may be varied depending on the type of the formulation.
  • a cosmetic composition according to the present invention comprises at least one cosmetically acceptable carrier
  • a pharmaceutical composition according to the present invention comprises at least one pharmaceutically acceptable carrier.
  • formulations in the form of ointments, pastes, creams or gels may comprise animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc, zinc oxide, or mixtures of these ingredients.
  • Spray may additionally comprise the customary propellants, for example, chlorofluorohydrocarbons, propane, butane, diethyl ether, or dimethyl ether.
  • solvents, solubilizers and emulsifiers for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyleneglycol, oils, in particular cottonseed oil, groundnut oil, maize germ oil, olive oil, castor oil and sesame seed oil, glycerol fatty esters, polyethylene glycol and fatty acid esters of sorbitan, and mixtures of the aforementioned may be mentioned.
  • solvents, solubilizers and emulsifiers for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyleneglycol, oils, in particular cottonseed oil, groundnut oil, maize germ oil, olive oil, castor oil and sesam
  • Suspension-type formulations according to the present invention may comprise liquid diluents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isosteary alcohols, polyoxyethylene sorbitol esters and poly oxyethylene sorbitan esters, micocrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, or mixtures of the aforementioned.
  • liquid diluents for example water, ethanol or propylene glycol
  • suspending agents for example ethoxylated isosteary alcohols, polyoxyethylene sorbitol esters and poly oxyethylene sorbitan esters, micocrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, or mixtures of the aforementioned.
  • Cleansing compositions according to the present invention may comprise aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosucinnate monoester, isothinate, imidazolium derivatives, methyltaurate, sarcocinate, fatty acid amide ether sulfate, alkyl amido betain, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanoline derivatives, ethoxylated glycerol fatty acid ester, or mixtures of the aforementioned.
  • Additional antioxidant ingredients can be selected from, without limitation, Ascorbic acid, Ascorbic acid derivatives, Glucosamine ascorbate, Arginine ascorbate, Lysine ascorbate, Glutathione ascorbate, Nicotinamide ascorbate, Niacin ascorbate, Allantoin ascorbate, Creatine ascorbate, Creatinine ascorbate, Chondroitin ascorbate, Chitosan ascorbate, DNA Ascorbate, Carnosine ascorbate, Vitamin E, various Vitamin E derivatives, Tocotrienol, Rutin, Quercetin, Hesperedin ( Citrus sinensis), Diosmin (Citrus sinensis), Mangiferin (Mangifera indica), Mangostin (Garcinia mangostana), Cyanidin ( Vaccinium myrtillus), Astaxanthin ( Haematococcus algae), Lutein ( Tagetes patula), Lycopene ( Lycopersicum
  • ingredients for improving blood micro-circulation can be added to compositions according to the present invention.
  • Suitabel non-limiting examples may be selected from Horse Chestnut Extract ( Aesculus hippocastanum extract)), Esculin, Escin, Yohimbine, Capsicum Oleoresin, Capsaicin, Niacin, Niacin Esters, Methyl Nicotinate, Benzyl Nicotinate, Ruscogenins (Butchers Broom extract; Ruscus aculeatus extract), Diosgenin ( Trigonella foenumgraecum, Fenugreek), Emblica extract ( Phyllanthus emblica extract), Asiaticoside ( Centella asiatica extract), Boswellia Extract ( Boswellia serrata), Ginger Root Extract ( Zingiber Officianalis), Piperine, Vitamin K, Melilot ( Melilotus officinalis extract), Glycyrrhetinic acid, Ursolic acid, Sericoside ( Terminalia sericea extract),
  • Anti-inflammatory ingredients suitable for use in the context of the present invention may be selected from the group consisting of Cyclo-oxygenase (for example, COX-1 or COX-2) or Lipoxygenase (for example, LOX-5) enzyme inhibitors such as Ascorbic acid, Ascorbic acid derivatives, Vitamin E, Vitamin E derivatives, Tocotrienol, Rutin, Quercetin, Hesperedin ( Citrus sinensis), Diosmin ( Citrus sinensis), Mangiferin ( Mangifera indica), Mangostin ( Garcinia mangostana), Cyanidin ( Vaccinium myrtillus), Astaxanthin ( Haematococcus algae), Lutein ( Tagetes patula), Lycopene ( Lycopersicum esculentum), Resveratrol ( Polygonum cuspidatum), Tetrahydrocurcumin ( Curcuma longa), Rosmarinic acid ( Rosmarinus officinalis), Hypericin ( Hypericum perforatum), Ellagic
  • Anti-inflammatory composition can additionally be selected from, but not limited to, Horse Chestnut Extract ( Aesculus hippocastanum extract)), Esculin, Escin, Yohimbine, Capsicum Oleoresin, Capsaicin, Niacin, Niacin Esters, Methyl Nicotinate, Benzyl Nicotinate, Ruscogenins (Butchers Broom extract; Ruscus aculeatus extract), Diosgenin ( Trigonella foenumgraecum, Fenugreek), Emblica extract ( Phyllanthus emblica extract), Asiaticoside ( Centella asiatica extract), Boswellia Extract ( Boswellia serrata), Sericoside, Visnadine, Thiocolchicoside, Grapeseed Extract, Ginger Root Extract ( Zingiber Officianalis), Piperine, Vitamin K, Melilot ( Melilotus officinalis extract), Glycyrrhetinic acid, Ursolic acid, Sericoside ( Terminalia se
  • compositions according to the present invention examples of which include zinc, copper, manganese, vanadium, chromium, cobalt, and iron.
  • compositions according to the present invention are for decreasing lipid production in sebocytes.
  • a composition as herein described, is manufactured using usual and known methods and processes, depending on form and intended end-use of the respective composition.
  • the present invention relates to the use of a composition, as herein described above, for decreasing lipid production in sebocytes.
  • the present invention also relates to a cosmetic method for decreasing lipid production in sebocytes or in the skin of an individual in need thereof, comprising contacting said sebocyte or skin with an effective amount, i.e. a lipid production-decreasing amount, as defined herein, of at least one compound according to Chemical Formula (I), as defined herein, or with at least one composition according to the present invention, as herein defined above.
  • an effective amount i.e. a lipid production-decreasing amount, as defined herein, of at least one compound according to Chemical Formula (I), as defined herein, or with at least one composition according to the present invention, as herein defined above.
  • contacting is meant to refer to the exposing of a sebocyte or the skin of an individual with an amount effective to bring about the desired effect, i.e. with a lipid production- decreasing amount, as herein defined, of at least one compound according to Chemical Formula (I) or at least one composition according to the present invention.
  • exposing is meant to refer to the application of at least one compound according to Chemical Formula (I), as herein defined and described, or of at least one composition, as herein defined and described, for instance in the form of a leave-on or rinse-off product composition, to said sebocytes or skin of an individual.
  • the uses, methods and compositions of the present invention thus relate to topical application of at least one compound according to Chemical Formula (I) or at least one composition, as herein described above, so as to treat, reverse, ameliorate and/or prevent signs of lipid overproduction on or within the skin.
  • the uses, methods and compositions of the present invention intended for decreasing lipid production in sebocytes and/or in the skin of an individual in need thereof, may comprise the topical application of at least one compound according to Chemical Formula (I) or at least one composition, as herein described above, over an affected area for a period of time sufficient to reduce, ameliorate, reverse or prevent dermatological signs of lipid over-production.
  • Areas affected by lipid overproduction include, but are not limited to oily areas of the skin, e.g., oily facial skin (especially in T-zone-forehead, nose, and chin) or an area of the scalp, as well as non-facial areas, such as the chest, neck, shoulders, and/or back.
  • the compounds according to Chemical Formula (I) of the present invention may provide such benefits through one or more activities including, but not limited to, decreasing triglyceride, wax ester, squalene and cholesterol levels in sebocytes, such as by bringing about one of more of a decrease in intracellular lipid and/or triglyceride, wax ester, squalene and cholesterol production, storage, and/or accumulation; and an increase in fatty acid oxidation, degradation and/or lipolysis.
  • the improvement in the condition and/or aesthetic appearance is selected from the group consisting of: reducing lipid production by sebaceous glands; reducing triglyceride synthesis; reducing wax ester synthesis; reducing squalene synthesis; reducing fatty acid synthesis; preventing and/or improving conditions related to skin associated with nonselective or partially selective FAS stimulators/up regulators, nonselective or partially selective acyl-CoA wax alcohol acyltransferase 1 (AWAT1 ) stimulators/up regulators, nonselective or partially selective squalene synthase (SQS) stimulators/up regulators; preventing, ameliorating or treating oily skin; preventing, ameliorating or treating oily hair; preventing, ameliorating or treating oily scalp; preventing, ameliorating or treating enlarged pores; preventing, ameliorating, or treating acne-prone skin; preventing, ameliorating or treating body odors associated with excess sebum production; and any combinations thereof.
  • the compounds, compositions, uses and methods of the present invention provide an anti-oil/sebum effect so as to produce a visible or palpable improvement in skin affected by excess sebum, i.e. lipid overproduction in sebocytes.
  • Such improvements include, without limitation, restoration of a matte finish to the skin; an evening of skin type; reduction in oily/greasy feel to skin and/or hair; reduction in the incidence of dandruff; reduction in the incidence of blocked/clogged pores; reduction in the incidence of comedones; reduction in the incidence of acne lesions; reduction in the area over producing lipids; reduction in thickness of skin affected by over-production of lipids.
  • an effective amount of a compound according to Chemical Formula (I) may be applied to exposed areas of the skin, such as in the form of a composition, as herein defined and described, and, if necessary, may then be spread over and/or rubbed into the skin using the hand or fingers or a suitable device.
  • the compound or composition comprising the same may be applied as frequently as needed to achieve the desired effects.
  • the composition may be applied daily, according to various embodiment multiple times per day, i.e. 2 or more times per day, such as at least three times per day, when an individual is experiencing the appearance of excess sebum to provide immediate relief and/or, eventually, maintain the desired complexion.
  • the compounds and/or compositions may be applied proactively and/or preventively to areas of the skin known to exhibit sebum overproduction. Such areas may include any area on the individual's skin he/she feels exhibits or in his/her personal experience exhibits over-production of lipids.
  • the methods, compounds, and compositions of the present invention may be used to prevent and/or reduce the incidence of various conditions such as acne and/or dandruff associated with hyper-seborrheic skin.
  • a reduction in the incidence of these conditions includes, but is not limited to, a reduction in the frequency, a reduction in the severity, and/or reduction of the area over which such conditions occur.
  • the compounds and/or compositions of the present invention are applied to skin in need of treatment, that is, skin which suffers from a deficiency or loss in any of the foregoing attributes, or which would otherwise benefit from improvement in any of the foregoing skin attributes.
  • the compounds and/or composition of the present invention are intended for use in non-therapeutic treatment methods.
  • the compounds and/or compositions are intended to be rubbed, poured, sprinkled, or sprayed on, or otherwise applied to the human body for cleansing, beautifying, attractiveness-promoting, or appearance-altering purposes.
  • Example 1 Lipid-production lowering efficiency of pure phenol compounds
  • the amount of lipid produced by sebocytes was determined by applying a fluorescent lipid dye to an Asian primary sebocyte cell line, and the fluorescent signal was measured using a fluorescent plate reader and flow cytometer in separate experiments. The fluorescent intensity for each compound treatment was compared against vehicle (DMSO) control treatment.
  • a sebocyte cell line derived from an Asian female donor was used for all experiments.
  • 30,000 sebocytes were seeded per 0.32 cm 2 along with the respective compound and incubated at 37 °C and 5 % CCte for 72 hours. After 3 days incubation, the media was discarded. The cells were fixed in 4 % paraformaldehyde for 20 minutes, then rinsed with an equal amount of PBS.
  • a solution of Hoechst and 3 % AdipoRed was used to stain for DNA content and neutral lipid respectively. Cells were incubated in the staining solution for 20 minutes at 37 °C and 5 % CO2. Cells were rinsed once with PBS, and fluorescence intensity for Hoechst and AdipoRed was measured by a fluorescence plate reader at excitation/emission wavelength of 350/461 nm and 485/572 nm, respectively.

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Abstract

La présente invention concerne des composés de phénol destinés à être utilisés dans un procédé de réduction de la production de lipides dans des sébocytes; des compositions comprenant au moins un tel composé ; l'utilisation d'une telle composition pour diminuer la production de lipides dans les sébocytes ; et un procédé cosmétique pour diminuer la production de lipides dans les sébocytes. Dans certains modes de réalisation, le composé est choisi dans le groupe constitué par le bakuchiol et le ptérostilbène.
PCT/SG2020/050366 2019-06-25 2020-06-25 Phénols qui diminuent la production de lipides dans des sébocytes Ceased WO2020263189A1 (fr)

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WO2023238058A1 (fr) * 2022-06-07 2023-12-14 Dyson Operations PTE. LTD. Compositions d'acide oléanolique pour la régulation du sébum
CN117247327A (zh) * 2023-10-13 2023-12-19 深圳市护家科技有限公司 补骨脂酚衍生物及其盐的制备方法和应用
WO2025083496A1 (fr) * 2023-10-19 2025-04-24 Dyson Operations PTE. LTD. Compositions pour la régulation du sébum
GB2641483A (en) * 2023-10-19 2025-12-10 Dyson Operations Pte Ltd Compositions for sebum control

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