Topical composition comprising feverfew

Tag : natural emulsifier


Abstract
This invention relates to a method of treating and preventinginflammatory disorders and related conditions using an extract offeverfew. Particularly, the invention includes a method of treatingand preventing inflammatory disorders and related conditions whichcomprises applying a topical composition comprising an effectiveamount of an extract of feverfew to a patient and a method oftreating and preventing inflammatory disorders and relatedconditions of the skin by applying a topical composition containingan effective amount of an extract of feverfew to a patient. Inaddition, the invention includes a method of treating andpreventing inflammatory disorders and related conditions byapplying a topical composition containing an effective amount of anextract of feverfew to a patient where said extract issubstantially free of .alpha.-unsaturated .gamma.-lactone.
Description of the Invention
SUMMARY OF THE INVENTION

This invention relates to a method of treating or preventinginflammatory disorders and related conditions using an extract offeverfew. More particularly, the invention includes a method oftreating or preventing inflammatory disorders and relatedconditions by applying a topical composition containing aneffective amount of an extract of feverfew to a patient. The methodof this invention includes a method of treating or preventinginflammatory disorders and related conditions of the skin byapplying a topical composition comprising an effective amount of anextract of feverfew to a patient. Still further, the inventionincludes a method of treating and preventing inflammatory disordersand related conditions by applying a topical composition containingan effective amount of an extract of feverfew to a patient wheresaid extract is substantially free of .alpha.-unsaturated.gamma.-lactone. Further, the invention includes a method oftreating and preventing inflammatory disorders and relatedconditions of the skin by applying a topical composition containingan effective amount of an extract of feverfew to a patient wheresaid extract is substantially free of .alpha.-unsaturated.gamma.-lactone.

DETAILED DESCRIPTION OF THE INVENTION

This invention includes a method of treating and preventinginflammatory disorders and related conditions by applying a topicalcomposition containing an effective amount of an extract offeverfew to a patient.

Inflammatory disorders and relate conditions which may be treatedor prevented by topical use of the compositions of this inventioninclude, but are not limited to the following: arthritis,bronchitis, contact dermatitis, atophic dermatitis, psoriasis,seborrheic dermatitis, eczema, allergic dermatitis, polymorphouslight eruptions, inflammatory dermatoses, folliculitis, alopecia,poison ivy, insect bites, acne inflammation, irritation induced byextrinsic factors including, but not limited to, chemicals, trauma,pollutants (such as cigarette smoke) and sun exposure, secondaryconditions resulting from inflammation including but not limited toxerosis, hyperkeratosis, pruritus, post-inflammatoryhyperpigmentation, scarring and the like. Preferably, theinflammatory disorders and related conditions which may be treatedor prevented using the methods of the invention are arthritis,inflammatory dermatoses, contact dermatitis, allergic dermatitis,atopic dermatitis, polymorphous light eruptions, irritation,including erythema induced by extrinsic factors, acne inflammation,psoriasis, seborrheic dermatitis, eczema, poison ivy, insect bites,folliculitus, alopecia, and secondary conditions and the like.

"Feverfew" is a plant belonging to the family ofAsteraceae/Composite which is technically known as, Tanacetumparthenium, Altamisa, Crisanthemum, Leucanthemum, or Pyrethrumparthenium.

The term "effective amount" refers to the percentage byweight of the feverfew extract in the topical composition which isneeded to treat an inflammatory disorder or related condition in apatient. Preferably the effective amount is between about 0.0005 toabout 20% by weight of the composition. More preferably, theconcentration should be less than about 10% by weight of thetopical composition. Even more preferably between about 0.001% andabout 10%, and most preferably between about 0.01% and about 2%.

The term "patient" refers to a mammal which is beingtreated prophylactically for an inflammatory condition and/or foran inflammatory condition with visible symptoms. Preferably thepatient is a human.

Further, the invention includes a method of treating and preventinginflammatory disorders and related conditions of the skin byapplying a topical composition containing an effective amount of anextract of feverfew to a patient.

The terms, inflammatory disorder and related condition, feverfew,effective amount, and patient, have their aforementioned meanings.The term "skin" includes all surfaces of a patient, suchas the exposed hide or surfaces covered by hair.

The invention also includes a method of treating and preventinginflammatory disorders and related conditions which comprisesapplying a topical composition comprising an effective amount of anextract of feverfew to a patient where said extract is.alpha.-unsaturated .gamma.-lactone-deprived.

The terms, inflammatory disorders and related conditions, feverfew,effective amount, and patient have their aforementioned meanings.The term "substantially free of .alpha.-unsaturated.gamma.-lactone", refers to an extract of feverfew having aweight content of the .alpha.-unsaturated .gamma.-lactones found innatural feverfew extracts of less than about 0.2% by weight. These.alpha.-unsaturated .gamma.-lactones include but are not limited toparthenolide ([1.alpha.R-(1a R*, 4E,7a S*,10a S*,10bR*)]2,3,4,7,7a,8,10a,10b-octahydro-1a,5-dimethyl-8-4,5.alpha.-epoxy-6.bet-a.-hydroxy-germacra-1(10),11(13)-dien-12-oic acid .gamma.-lactone),3-.beta.-hydroxy-parthenolide, costunolide, 3-.beta.-constunolide,artemorin, 8.alpha.-hydroxy-estafiatin, chysanthemolide,magnoliolide, tanaparthin, tanaparthin-1.alpha.,4.alpha.-epoxide,tanaparthin-1.beta.,4.beta.-epoxide, chrysanthemonin, and othersesquiterpenes. Preferably, the feverfew extract has a weightcontent of .alpha.-unsaturated .gamma.-lactone below about 0.2.Preferably the .alpha.-unsaturated .gamma.-lactone is parthenolide.The method of preparing this parthenolide-deprived extract isdescribed in an Italian patent application (MI99A001244, filed onJun. 3, 1999) which is hereby incorporated by reference. Since the.alpha.-unsaturated .gamma.-lactones cause some of the allergicreactions to extracts of feverfew, topical compositions made from.alpha.-unsaturated .gamma.-lactone-deprived extracts are expectedto be non-irritating.

This invention also includes a method of treating inflammatorydisorders and related conditions of the skin by applying a topicalcomposition comprising an effective amount of an extract offeverfew to a patient where said extract is substantially free of.alpha.-unsaturated .gamma.-lactone.

The terms inflammatory disorders and related conditions, feverfew,effective amount, paiie-nt, skin-, and .alpha.-unsaturated.gamma.-lactone-deprived have their aforementioned meanings.

In addition to the extracts of feverfew, other substances, such asbiologically active agents, pharmaceutical excipients, and cosmeticagents may be included in the topical compositions of thisinvention.

Biologically active agents may include, but are not limited to,flavanoid/flavone compounds which include but are not limited totanetin, 3,7,3'-trimethoxyquercetagetin, apigenin and itsderivatives. When flavanoid/flavone compounds are present, they arepresent at a concentration of between about 0.001% to about 0.5%preferably, between about 0.005% and 0.2% based on the weight ofthe topical composition.

Additional biologically active agents include but are not limitedto sunscreens, anti-wrinkling/antiaging agents, antifungal agents,antibiotic agents, anti-acne and antipsoriatic agents,depigmentating agents, where such agents may be utilized so long asthey are physically and chemically compatible with the othercomponents of the topical composition.

The compositions of this invention may include additional skinactives. Actives can be but not limited to vitamin compounds. Skinlightening agents (kojic acid, ascorbic acid and derivatives suchas ascorbyl pamiltate, and the like); anti-oxidant agents such astocopherol and esters; metal chelators, retinoids and derivatives,moisturizing agents, hydroxy acids such as salicylic acid, sunscreen such as octyl methoxycinnamate, oxybenzone, avobenzone, andthe like, sun blocks such as titanium oxide and zinc oxide, andskin protectants. Mixtures of above skin actives may be used.

Sunscreens which may be used in the compositions of this inventionmay include but are not limited to organic or inorganic sunscreens,such as, octylmethoxycinnamate and other cinnamate compounds,titanium dioxide, zinc oxide and the like.

Anti-wrinkling/anti-aging agents may include but are not limited toretinoids (for example, retinoic acid, retinol, retinal, retinylacetate, and retinyl palmitate) alpha hydroxy acids, galactosesugars (for example, melibiose and lactose), antioxidants,including but not limited to water soluble antioxidants such assulfhydryl compounds and their derivatives (for example, sodiummetabisulfite and N-acetyl-cysteine, acetyl-cysteine), lipoic acidand dihydrolipoic acid, resveratrol, lactoferin, ascorbic acid andascorbic acid derivatives (for example ascorbyl palmitate andascorbyl polypeptide). Oil soluble antioxidants suitable for use inthe compositions of this invention include, but are not limited totocopherols (for example, tocopheryl acetate, .alpha.-tocopherol),tocotrienols and ubiquinone. Natural extracts containingantioxidants suitable for use in the compositions of thisinvention, include, but not limited to extracts containingflavonoids, phenolic compounds, flavones, flavanones,isoflavonoids, mono, di- and tri-terpenes, sterols and theirderivatives. Examples of such natural extracts include grape seed,green tea, pine bark and propolis extracts and legume extracts andthe like.

Antifungal agents include but are not limited to miconazole,econazole, ketoconazole, itraconazole, fluconazole, bifoconazole,terconazole, butoconazole, tioconazole, oxiconazole, sulconazole,saperconazole, clotrimazole, undecylenic acid, haloprogin,butenafine, tolnaftate, nystatin, ciclopirox olamine, terbinafine,amorolfine, naftifine, elubiol, griseofulvin, and theirpharmaceutically acceptable salts.

Antibiotic (or antiseptic agents) include but are not limited tobut are not limited to mupirocin, neomycin sulfate, bacitracin,polymyxin B, l-ofloxacin, tetracyclines (chlortetracyclinehydrochloride, oxytetracycline hydrochloride and tetrachcyclinehydrochoride), clindamycin phosphate, gentamicin sulfate,benzalkonium chloride, benzethonium chloride, hexylresorcinol,methylbenzethonium chloride, phenol, quaternary ammonium compounds,triclocarbon, triclosan, tea tree oil, benzoyl peroxide and theirpharmaceutically acceptable salts.

Acne ingredients include but are not limited to agents thatnormalize epidermal differentiation (e.g. retinoids), keratolyticagents (e.g. salicylic acid and alpha hydroxy acids), benzoylperoxide, antibiotics and compounds or plant extracts that regulatesebum.

Antipsoriatic agents include but are not limited to corticosteroids(e.g., betamethasone dipropionate, betamethasone valerate,clobetasol propionate, diflrasone diacetate, halobetasolpropionate, amcinonide, desoximetasone, fluocinonide, fluocinoloneacetonide, halcinonide, triamcinolone acetate, hydrocortisone,hydrocortisone valerate, hydrocortisone butyrate, aclometasonedipropionte, flurandrenolide, mometasone furoate,methylprednisolone acetate), Vitamin D and its analogues (e.g.calcipotriene), retinoids (e.g. Tazarotene) and anthraline.

Cosmetic agents which may be used in the compositions of thisinvention may include, but are not limited to those agents whichprevent potential skin irritation, such as emollients, vitamins andantioxidants (e.g., vitamin E) and herbal extracts (e.g., aloevera). Further, the cosmetic agents may include humectants,antioxidants/preservatives, plant extracts, flavors, fragrances,surface active agents, and the like. Examples of humectants includeglycerol, sorbitol, propylene glycol, ethylene glycol, 1,3-butyleneglycol, polypropylene glycol, xylitol, maltitol, lactitol, oatprotein, allantoin, acetamine MEA, hyaluronic acid and the like.They may be used either singly or in combination.

Cosmetic agents may also include substances which mask the symptomsof inflammatory disorders and related conditions; such substancesinclude but are not limited to pigments, dyes, and other additives(e.g., silica, talk, zinc oxide, titanium oxide, clay powders). Thepharmaceutical excipients include but are not limited to pHmodifying agents such as pH-modifying agents, organic solvents(e.g., propylene glycol, glycerol, etc.), cetyl alcohol, kaolin,talc, zinc oxide, titanium oxide, cornstarch, sodium gluconate,oils (e.g., mineral oil), ceteareth-20, ceteth-2, surfactants andemulsifiers, thickener (or binders), perfume, antioxidants,preservatives, and water.

Binders or thickeners may be used in the compositions of thisinvention to provide substantivity and physical stability to thecompositions. Binders or thickeners suitable for use in thecompositions of this invention include cellulose derivatives suchas alkali metal salts of carboxymethylcellulose, methyl cellulose,hydroxyethyl cellulose and sodium carboxymethylhydroxyethylcellulose, alkali metal alginates such as sodium alginate,propylene glycol alginate, gums such as carrageenan, xanthan gum,tragacanth gum, caraya gum and gum arabic, and synthetic binderssuch as polyvinyl alcohol, polysodium acrylate and polyvinylpyrrolidone. Thickeners such as natural gums and syntheticpolymers, as well as coloring agents and fragrances also arecommonly included in such compositions.

Examples of preservatives which may be used in the compositions ofthis invention include, but are not limited to, salicylic acidschlorhexidine hydrochloride, phenoxyethanol, sodium benzoate,methyl para-hydroxybenzoate, ethyl para-hydroxybenzoate, propylpara-hydroxybenzoate, butyl para-hydroxybenzoate and the like.

Examples of flavors and fragrances which may be used in thecompositions of this invention include menthol, anethole, carvone,eugenol, limonene, ocimene, n-decylalcohol, citronellol,a-terpineol, methyl salicylate, methyl acetate, citronellylacetate, cineole, linalool, ethyl linalool, vanillin, thymol,spearmint oil, peppermint oil, lemon oil, orange oil, sage oil,rosemary oil, cinnamon oil, pimento oil, cinnamon leaf oil, perillaoil, wintergreen oil, clove oil, eucalyptus oil and the like.

The compositions of the present invention may be prepared in anumber of forms for topical application to a patient. For example,the composition may be applied in a gel, cream, ointment, shampoo,scalp conditioners, liquid, spray liquid, paint-/brush-onpreparation, aerosol, powder or adhesive bandage. In addition thecomposition may be impregnated on a bandages, hydrocolloiddressing, treatment patch or on cloth wipe products, such as babywipes or facial wipes.

The compositions of this invention may be in the form of emulsions,such as creams, lotions and the like. Such compositions may havemore than one phase and may include surface active agents whichenable multiphase emulsions to be manufactured.

Examples of surface active agents which may be used in thecompositions of this invention include sodium alkyl sufates, e.g.,sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acylsarcosinates, e.g., sodium N-lauroyl sarcosinate and sodiumN-myristoyl sarcosinate, sodium dodecylbenzenesulfonate, sodiumhydrogenated coconut fatty acid monoglyceride sulfate, sodiumlauryl sulfoacetate and N-acyl glutamates, e.g., N-palmitoylglutamate, N-methylacyltaurin sodium salt, N-methylacylalaninesodium salt, sodium a-olefin sulfonate and sodiumdioctylsulfosuccinate; N-alkylaminoglycerols, e.g.,N-lauryldiaminoethylglyecerol andN-myristyldiaminoethylglycerol,N-alkyl-N-carboxymethylammoniumbetaine and sodium 2-alkyl-1-hydroxyethylimidazoline betaine;polyoxyethylenealkyl ether, polyoxyethylenealkylaryl ether,polyoxyethylenelanolin alcohol, polyoxyethyleneglycerylmonoaliphatic acid ester, polyoxyethylenesorbitol aliphatic acidester, polyoxyethylene aliphatic acid ester, higher aliphatic acidglycerol ester, sorbitan aliphatic acid ester, Pluronic typesurface active agent, and polyoxyethylenesorbitan aliphatic acidesters such as polyoxyethylenesorbitan monooleate andpolyoxyethylenesorbitan monolaurate. Emulsifier-type surfactantsknow to those of skill in the art should be used in thecompositions of this invention.

Another important ingredient of the present invention is adermatologically acceptable carrier. Such a suitable carrier isadequate for topical use. It is not only compatible with the activeingredients described herein, but will not introduce any toxicityand safety issues. An effective and safe carrier varies from about50% to about 99% by weight of the compositions of this invention,more preferably froma bouat 75% to about 99% of the compositionsand most preferably from about 85% to about 95% by weight of thecompositions.

The choice of which pharmaceutical excipient or biological agent,or cosmetic agent to use is often controlled or affected by thetype of inflammatory disorder or related condition which is beingtreated. For example, if the compositions of this invention wereused to treat a skin inflammation associated with athlete's foot,jock itch or diaper rash, talc would be a preferred pharmaceuticalexcipient and an antifungal agents would be preferred biologicalagents. If the compositions of this invention were to be used totreat eczema of the scalp, emulsifiers and oils would be preferredpharmaceutical excipients.

The condition of contact dermatitis may be treated by applying atopical composition comprising a feverfew extract where saidextract has 1% of feverfew which is substantially free ofparthenolides, i.e., the parthenolide concentration of said extractis <0.1%. Due to the extremely low concentration of parthenolidein such a feverfew extract, atopic composition made from thisextract will be non-irritating.

Claim 1 of 26 Claims
1. A topical composition comprising an effective amount of anextract of feverfew and a pharmaceutically acceptable excipient,wherein said extract is substantially free of .alpha.-unsaturated.gamma.-lactone.

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