sign in sign up
<<
Home , Demecolcine

US 200701 40999A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0140999 A1 Puglia et al. (43) Pub. Date: Jun. 21, 2007

(54) TOPCAL SKIN CARE COMPOSITION tinuation-in-part of application No. 10/622,560, filed CONTAINING REFINED PEANUT OIL on Jul. 18, 2003, now abandoned. (75) Inventors: Nancy Puglia, Sanford, FL (US); Jerry Publication Classification Roth, Sanford, FL (US); Rosario Ramirez, Sanford, FL (US) (51) Int. C. A6IR 36/48 (2006.01) Correspondence Address: A 6LX 3L/7072 (2006.01) BELL, BOYD, & LLOYD LLP A6II 3L/203 (2006.01) P.O. BOX 1135 CHICAGO, IL 60690 (US) (52) U.S. Cl...... 424/62; 424/757: 514/559; (73) Assignee: Hill Dermaceuticals, Inc., Sanford, FL 514/731: 514/49 (21) Appl. No.: 11/668,257 (57) ABSTRACT (22) Filed: Jan. 29, 2007 Related U.S. Application Data A vehicle containing refined peanut oil for topical use in skin care and for use in skin care therapeutics, and a process for (60) Division of application No. 10/892,153, filed on Jul. making the vehicle and a composition and therapeutic 16, 2004, now Pat. No. 7,169,401, which is a con composition made from that process. US 2007/O 140999 A1 Jun. 21, 2007

TOPCAL SKN CARE COMPOSITION use on keratinized or cornified skin, as compared to non CONTAINING REFINED PEANUT OL keratinized or mucous membranes as found in the mouth, 0001. This application is a continuation-in-part of U.S. esophagus, anus and Vagina. Ser. No. 10/662,560 filed 18 Jul. 2003. This application also 0009. It has been suspected that creams containing peanut claims benefit to U.S. Ser. No. 60/507,117 filed 1 Oct. 2003. oil may be a cause of nut allergy (Lever, British Medical Journal 313:299-300, 1996). A recent study revealed that FIELD OF THE INVENTION infants sensitized to peanuts might have been exposed to peanut oil (Lack et al., New England Journal of Medicine 0002 The invention relates generally to medicated skin 348:977-985, 2003). Yet, peanut oil can be found in certain treatment compositions and more particularly to a vehicle, compositions. Such as in injectables, where the oil serves as Such as a cream, lotion, balm, ointment, gel and the like a reservoir of a drug. Thus, there remains no appreciation of containing a medicament for the treatment of a skin condi employing peanut oil that is non-allergenic, and there is no tion. appreciation of the skin hydrating properties of non-aller BACKGROUND OF THE INVENTION genic, refined peanut oil in a topical formulation. 0010. The refined peanut oil of interest is commercially 0003 Medicinal topical preparations can serve as drug available (Welch, Holme & Clark, Newark, N.J.). A refined delivery means. The vehicles thereof carry the pharmaco peanut oil of interest is one that is suitable for pharmaceu logically active agents to the skin, but also can serve as a tical use and is substantially free of proteins, and particularly depot for delivery of the drugs intradermally or transder those proteins known to be allergenic in humans, such as the mally. area h glycoproteins. Thus, a peanut oil of interest is treated 0004) Other topical preparations do not serve to deliver a to deactivate, to remove the biological activity, and at the therapeutic agent but may serve to treat various skin con least, the immunogenicity of Such proteins and thus essen ditions, by, for example, softening of the skin, tightening of tially is hypoallergenic and preferably non-allergenic. the skin or moisturizing the skin. 0011 For example, a refined peanut oil of interest is 0005 There remains a need in the art for a therapeutic treated with alkali (or other refining solution) and/or heat. product and approach that can contain one or more active Many peanut oil impurities, including the proteinaceous agents or medicines using a vehicle with beneficial proper allergens can be hydrated, and then separated. A water ties. Such a vehicle, for example, a cream, would be one that washing can be used to remove such impurities, the bulk of has hydrating effects on human skin. Such a therapeutic which often are removed in the form of soaps, with the carrier would ameliorate any drying, irritating or debilitating proteins attached or associated with the Soaps. Alternatively, effect of the medicaments on the skin and thus, make the proteins and the like which are water soluble, are removed course of treatment more tolerable for the patient, improving by partitioning into the aqueous phase. patient compliance and thus, the therapeutic effectiveness of 0012. The refined peanut oil of interest optionally then the pharmaceutically active agent(s). can be bleached to remove other impurities, such as colored compounds and other remaining impurities. Generally, the SUMMARY OF THE INVENTION bleaching process involves adsorption onto a carrier, such as 0006 The invention provides a skin care composition activated carbon or a silicate, such as clay, Such as bentonite. containing hypoallergenic or non-allergenic or refined pea Generally the refined oil is passed over a bed of adsorbent nut oil for topical application to the skin and particularly or the adsorbent is mixed in the oil and then removed. keratinized skin. The invention also provides a preparation 0013 The refined peanut oil of interest optionally then containing non-allergenic or refined peanut oil for the topi can be further treated with a steam distillation process, often cal application of a medicament to the skin and particularly under vacuum. keratinized skin. The medicament can be a skin care thera peutic. The invention also provides a process for making the 0014) A refined peanut oil of interest can be exposed to all vehicle. three of the above treatments, in the order of refining, bleaching and then vacuum steam distillation. DETAILED DESCRIPTION OF THE 0015. A refined peanut oil of interest can be treated by INVENTION other methods, the goal being to inactivate or remove the 0007. The instant invention relates to a novel and useful peanut oil allergens. vehicle for topical non-pharmaceutical and pharmaceutical 0016 Inactivation of the peanut oil allergens can be applications. The topical vehicle is a mixture, Suspension or monitored using any of a variety of methods, for example, emulsion of a variety of hydrophobic and hydrophilic the tests available from Neogen (Lansing, Mich.). Antibody reagents. The instant formulation can be in the form of a to the various areah glycoproteins is commercially available cream, paste, unguent, lotion, ointment, gel, serum, balm, or can be made practicing known immunology methods. salve, mousse, and other known compositions. Both polyclonal or monoclonal antibodies can be made and 0008. The instant topical vehicle is one that carries supe used. Current commonly used antibodies are polyclonal, rior and unexpected properties, such as excellent skin being raised to a collection of peanut protein, and thus to a hydrating properties, and Such properties are obtained by the variety of allergens. The use of such antibodies for the inclusion of a non-allergenic, refined peanut oil in the detection of peanut allergens can rely on any of the known vehicle. To obtain the enhanced skin hydrating properties of assay formats, such as an ELISA. Commercially available a formulation of interest, the topical vehicle preferably is for tests can detect as little as 2.5 parts per million (ppm) of US 2007/O 140999 A1 Jun. 21, 2007

peanut protein. Using an antibody directed to peanut pro animals, plant seeds and nuts are similar to fats and conse teins in an ELISA, the refined peanut oil of interest was quently, and can contain one or a significant number of one found to contain less than 1 ppm of peanut protein. or more polar acids and/or ester groups. Alternatively, oils derived from petroleum are usually aliphatic or aromatic 0017 Most topical preparations are substantially lipo hydrocarbons that are essentially free of polar substitution philic but also may be an emulsion of both lipophilic and hydrophilic ingredients. An artisan would well recognize and therefore may be preferred for certain applications. It is how to formulate Such topical preparations containing preferable for the oil to be refined so as to be compatible refined peanut oil comprising hydrophilic reagents and with human tissue. hydrophobic (or lipophilic) reagents. 0023. Other oil-based products that can be used include hydrocarbons or mineral fats obtained by the distillation of 0018. The topical preparation of interest contains at least petroleum (petroleum jelly): vegetable oils and liquid trig 1% by weight of refined peanut oil, at least 2% by weight, lycerides; animal fats or solid natural triglycerides; and at least 3% by weight, at least 4% by weight, at least 5% by waxes or Solid ethers of fatty acids and organic alcohols. weight, at least 6% by weight, at least 7% by weight, at least Lanolin or wool fats that are obtained from sheep wool and 8% by weight, at least 9% by weight or at least 10% by made up of fatty acids and cholesterol esters; and cetyl and weight of refined peanut oil. stearyl alcohols, which are solid alcohols obtained by hydro 0019. The topical formulation can contain at least 15% by genation of their respective acids are also useable. weight of refined peanut oil, at least 20%, at least 25%, at Amphiphilic compounds such as Soaps or salts offatty acids, least 30%, at least 35%, at least 40%, at least 45% or at least that may be acidic or basic depending on whether the 50% or more by weight of refined peanut oil. The properties lipophilic group is anionic or cationic, Sulfated alcohols of the final vehicle and the compatibility thereof with the one which are semi-synthetic Substances and synthetic Surface or more pharmaceutically active agents incorporated therein active agents are known in the art and can be used in the will determine the amount of refined peanut oil used. topical preparation of interest. Glycerine is obtained from fats and, due to its hydrophobicity, has the property of 0020. The compositions of the instant invention can extracting water from the Surface of the mucosa or denuded comprise a wide range of components as known in the art. skin. Glycerin does not damage intact skin. Because glyc The “CTFA Cosmetic Ingredient Handbook’, Second Edi erine has hydrophilic properties, it is a useful humectant in tion, 1992, which is incorporated by reference herein in its a preparation of interest. entirety, describes a wide variety of cosmetic and pharma ceutical ingredients commonly used in the skin care indus 0024. Other materials that may be used in a topical try, which are suitable for use in the compositions of the preparation of interest include liquid alcohols, liquid gly instant invention. Reference also can be made to U.S. Pat. cols, liquid polyalkylene glycols, liquid esters, liquid Nos. 6,013,271; 6,267,985; 4,992,478; 5,645,854; 5,811, amides, liquid protein hydrosylates, liquid alkylated protein 111; and 5,851,543. Examples of functional classes of hydrosylates, liquid lanolin and lanolin derivatives, and ingredients are absorbents, abrasives, anti-acne agents, anti other like materials. Particular examples include monohy caking agents, antifoaming agents, antimicrobial agents, dric and polyhydric alcohols, e.g., ethanol, isopropanol, antioxidants, binders, biological additives, buffering agents, glycerol, Sorbitol, 2-methoxyethanol, diethylene glycol, eth such as sodium hydroxide, sodium citrate and EDTA, bulk ylene glycol, hexylene glycol, mannitol, cetyl alcohol and ing agents, chelating agents, chemical additives, colorants, propylene glycol; ethers, such as diethyl or dipropyl ether; cosmetic astringents, cosmetic biocides, denaturants, dis polyethylene glycols and methoxypolyoxyethylenes; carbo persants, deodorants, lubricants, drug astringents, external waxes having molecular weights ranging from 200 to analgesics, fragrance components, such as menthol, mois 20,000; polyoxyethylene glycerols; polyoxyethylene; sorbi turizers, flavorants, humectants, thickeners, such as car tols; and Stearoyl diacetin. The topical carriers often include boxymethylcellulose, opacifying agents, plasticizers, preser both an alcohol and water so as to accommodate lipophilic Vatives, such as dichlorobenzyl alcohol, benzoic acid, and hydrophilic components. methylparaben and phenyl, propellants, reducing agents, 0025. A number of different emulsifiers or surfactants can skin bleaching agents, opacifiers, such as Zinc oxide, mag be used to prepare a topical preparation of interest. Emul nesium aluminum silicate and titanium dioxide, skin-condi sifiers can be ionic or non-ionic. Examples of amphoteric tioning agents (emollients, humectants, miscellaneous and Surfactants useful in the compositions of the instant inven occlusive), skin protectants, solvents, foam boosters, hydro tion include those disclosed in McCutcheons, “Detergents tropes, Solubilizing agents, Suspending agents (nonsurfac and Emulsifiers”, North American edition (1986) and tant), gelling agents, such as petrolatum and mineral wax, McCutcheons, "Functional Materials”, North American Sunscreen agents, ultraviolet light absorbers, and viscosity Edition (1992); both of which are incorporated by reference increasing agents (aqueous and nonaqueous). herein in their entirety. Surfactants that can used include the betaines, Sultaines and hydroxysultaines. Examples of 0021. In addition, the topical carrier may include a pen betaines include the higher alkyl betaines, such as coco etration enhancer defined as a material that increases the dimethyl carboxymethyl betaine, lauryl dimethyl carboxym permeability of the skin to one or more active agents so as ethyl betaine, lauryl dimethyl alphacarboxyethyl betaine, to enhance permeability of one or more active agents, such cetyl dimethyl carboxymethyl betaine, cetyl dimethyl as dimethylsulfoxide, dimethyl formamide, dimethylaceta betaine, lauryl bis-(2-hydroxyethyl)carboxymethyl betaine, mide, decylmethylsulfoxide and polyethylene glycols. steryl bis-(2-hydroxypropyl) carboxymethyl betaine, oleyl 0022 Lipids may be used in a topical preparation of dimethyl gamma-carboxypropyl betaine, lauryl bis-(2-hy interest. As is known in the art, oils may be derived from droxypropy 1)alpha-carboxyethyl betaine, coco dimethyl animals, plants, nuts, petroleum etc. Those derived from sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, US 2007/O 140999 A1 Jun. 21, 2007

stearyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl thereof including cortodoxone, flucetonide, fludrocortisone bis-(2-hydroxyethyl) sulfopropyl betaine, and amidobe acetate, flurandrenolone acetonide, medrysone; prednisone, taines and amidosulfobetaines, oleyl betaine, and cocami and derivatives thereof including amcinafal, dopropyl betaine). Examples of Sultaines and hydroxysul amcinafide, betamethasone benzoate, Valerate and dipropi taines include cocamidopropyl hydroxysultaine. Examples onate, chloroprednisone acetate, descinalone acetonide, des of other amphoteric Surfactants are alkyliminoacetates, imi onide, , dichlorisone acetate, difluprednate, nodialkanoates and aminoalkanoates. flucloronide, flumethasone, flunisolide acetate, fluocinolone acetonide, fluocinonide, fluocortolone, , 0026. Examples of anionic surfactants also are disclosed fluperoline acetate, fluprednisolone Valerate, meprednisone, in McCutcheons, “Detergents and Emulsifiers', North methyl prednisolone, parametbaSone acetate, prednisolo American edition (1986) and McCutcheons, “Functional mate, prednisolone acetate, butylacetate and phosphate Materials”, North American Edition (1992). Examples Sodium, triamcinolone acetonide, hexacetonide, diacetate, include the alkoylisethionates, and the alkyl and alkyl ether hydrocortisone butyrate, flumethasone pivalate, halcininide Sulfates, such as, ammonium cocoyl isethionate, sodium and clobetasol propionate. cocoyl isethionate, sodium lauroyl isethionate, sodium Stearoyl isethionate and mixtures thereof, the sarcosinates, 0030 Examples of other active ingredients that can be Such as Sodium lauroyl sarcosinate, sodium cocoyl sarcosi used in a topical preparation of interest include acebutolol. nate, and ammonium lauroyl sarcosinate, sodium lauryl acetaminophen, acetohydoxamic acid, acetophenazine, acy Sulfate, ammonium lauryl Sulfate, ammonium cetyl sulfate, clovir, allopurinol, alprazolam, aluminum hydrexide, aman Sodium cetyl Sulfate, sodium Stearyl Sulfate, ammonium tadine, ambenonium, amiloride, aminobenzoate potassium, cocoyl isethionate, sodium lauroyl isethionate, sodium lau amobarbital, amoxicillin, amphetamine, amplicillin, andro royl sarcosinate, and mixtures thereof. gens, anesthetics, anticoagulants, anticonvulsants, antithy roids, appetite Suppressants, aspirin, atenolol, atropine, aza 0027. The instant vehicle can be used alone or as a carrier tadine, bacampicillin, baclofen, beclornethasone, for one or more pharmaceutically active agents for topical belladonna, bendroflumethiazide, benzoyl peroxide, benz use, preferably on keratinized skin. Examples of active thiazide, benztropine, bethanechol, biperiden, bisacodyl, agents include, Vitamins, such as A, D, E and K, corticos bromocriptine, bromodiphenhydramine, brompheniramine, teroids, hormones, anti-metabolites, cytostatic agents, alky buclizine, burnetanide, , butabarbital, butaperazine, lating agents, antimicrobials, such as antibacterials, antifun caffeine, calcium carbonate, captopril, arbamazepine, carbe gals and antivirals, keratolytics and the like. The amounts of nicillin, carbidopa & levodopa, carbinoxamine inhibitors, the active agent are as known in the art or which can be carbonic anhydrase, carisoprodol, carphenazine, cascara, determined empirically as known in the art. cefaclor, cefadroxil, cephalexin, cephradine, chliophedianol, 0028. A wide variety of cytostatic agents may be used. chloral hydrate, , chloramphenicol, chlordiaz Examples include alkylating agents, enzyme inhibitors, pro epoxide, chloroquine, chlorothiazide, chlorotianisene, chlo liferation inhibitors, DNA synthesis inhibitors, lytic agents, rpheniramine, , chlorpropamide, chlorpro DNA intercalators, and the like. Illustrative thixene, chlorthalidone, chlorZoxaZone, cholestyramine, agents include steroids, , ionomycin, , cimetidine, cinoxacin, clemastine, clidinium, , such as , , , clofibrate, clomiphere, clonidine, cloraZepate, cloxacillin, actinomycin D. meclorethamine, buSulfan, chlorambucil, , coloestlipol, estrogens, contraceptives, andro cactinomycin, carzinophilin, chlornaphazine, 6-chloropu gens, cromolyn, cyclacillin, cyclandelate, cyclizine, rine, azathioprine, , hydroxyurea, thioguanine, cyclobenzaprine, , cyclothiazide, , mitomycin, , , canthari cycrimine, cyproheptadine, danazol, danthron, dantrolene, din, camptothecin, , ricin, pseudomonas exo dapsone, dextroamphetamine, dexchlorpheniramine, dex toxin, interferons, interleukins, TNF, , methchlo tromethorphan, diazepan, , dicyclomine, dieth rethamine, , nitracine, nitoxantrone, ylstilbestrol, diflunisal, digitalis, diltiazen, dimenhydrinate, , nogalamycin, Streptonigrin, Streptozocin, dimethindene, diphenhydramine, diphenidol, diphenoxylate, , tetramin, , demecolcine and dactinomy diphenylopyraline, dipyradamole, disopyramide, disulfiram, cin. Other compounds that can be used include cytophamide, divalporex, calcium, docusate potassium, docusate cyclosporin, , biantrene hydrochloride, camo.stat Sodium, doxyloamine, dronabinol ephedrine, epinephrine, mesylate, campothecin, enocitabine, etoposide, ergoloidmesylates, ergonovine, ergotamine, , hydrochloride, phosphate, flutamide, fotemus estropipute, etharynic acid, ethchlorVynol, ethopropazine, tine, hydrochloride, ionomycin, onidaminie, ethoSaximide, ethotoin, fenoprofen, ferrous fumarate, fer mitoxantronie hydrochloride, nilutamide, paclitaxel, piraru rous gluconate, ferrous Sulfate, flavoxate, flecainide, bicin, toremifene, , didemnin, bactracyclin, mito fluphenazine, fluprednisolone, flurazepam, folic acid, furo quidone, penclomedine, phenazinomycin, U-73975, Sain semide, gemfibrozil, glipizide, glyburide, glycopyrrolate, topin, 9-aminocamptothecin, amonafide, merbarone and the gold compounds, griseofuwin, guaifenesin, guanabenz, gua like. Additional agents that can be used include mitomycin nadrel, guanethidine, halazepam, haloperidol, , C, , mechlorethamine, pyrazine diaZohydroxide, hexobarbital, hydralazine, hydrochlorothiazide, hydroflun fumagillin, rhyZOXin, dynemicin A, chlorambucil, Semustine ethiazide, hydroxychloroquine, hydroxy Zine, hyoscyamine, and the like. ibuprofen, indapamide, indomethacin, insulin, iofoquinol, iron-polysaccharide, isoetharine, isoniazid, isopropamide, 0029 Corticosteroids including halogenated corticoster isoproterenol, isotretinoin, isoxSuprine, kaolin, pectin, keto oids that can be used in the topical preparations of interest conazole, lactulose, levodopa, lincomycin, liothyronine, lio generally are known and are commercially available. trix, lithium, loperamide, lorazepam, magnesium hydroxide, Examples include cortisone, hydrocortisone and derivatives magnesium Sulfate, magnesium trisilicate, maprotiline, US 2007/O 140999 A1 Jun. 21, 2007 , medofenamate, medroxyproyesterone, melena 0033 Examples of non-steroidal anti-inflammatories that mic acid, , mephenyloin, mephobarbital, mep can be used in the instant invention include propionic acid robamate, , mesoridazine, metaproterenol, derivatives; acetic acid derivatives; fenamic acid deriva metaxalone, methamphetamine, methaqualone, metharbital, tives; biphenylcarboxylic acid derivatives; and oxicams, and methenamine, methicillin, methocarbamol, methotrexate, include acetyl salicylic acid, ibuprofen, naproxen, benox methSuximide, methyclothinzide, methylcellulose, methyl aprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, dopa, methylergonovine, methylphenidate, methylpredniso indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, lone, methysergide, metoclopramide, metolaZone, meto microprofen, tioxaprofen, Suprofen, alminoprofen, tiapro prolol, metronidazole, minoxidil, , monamine fenic acid, fluprofen and bucloxis acid. oxidase inhibitors, nadolol, , nalidixic acid, 0034) Examples of topical anesthetic drugs that can be naproxen, narcotic analgesics, neomycin, neostigmine, nia used in the topical preparation of interest include ben cin, , , nitrates, nitrofurantoin, Zocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, nomifensine, nylidrin, nystatin, orphenadrine, oxacillin, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, oxazepam, oXprenolol, oxymetazoline, oxyphenbutaZone, procaine, cocaine, ketamine, pramoxine, phenol, and phar pancrelipase, pantothenic acid, papaverine, paraminosali maceutically acceptable salts thereof. cylic acid, paregoric, pemoline, penicillamine, penicillins, pentobarbital, perphenazine, phenacetin, phenazopyridine, 0035) Some medicaments, pharmaceuticals and drugs pheniramine, , phenolphthalein, phenprocou that can be used for dermatological uses, or which previ mon, phensuximide, phenylbutaZone, phenylephrine, phe ously may not have been amenable to dermatologic use for nylpropanolamine, phenyl toloxamine, phenyloin, pilo any of a variety of reasons, can be irritating to the skin or can carpine, pindolol, piperacetatine, piroxicam, poloxamer, have other debilitating effects. For example, fluorouracil is polycarbophil calcium, polythiazide, potassium Supple irritating to skin. ments, pruzepam, prazosin, primidone, probenecid, probu 0036) The refined peanut oil-containing formulations of col, procainamide, , prochlorperazine, procy interest can overcome or mitigate those side effects because clidine, prornazine, promethazine, propantheline, of the unexpected and beneficial skin hydrating property of propranolol, pseudoephedrine, psoralens, psyllium, pyri refined peanut oil. The formulations of interest enhance dostigmine, pyrodoxine, pyrilamine, pyrvinium, quinestrol, intradermal and transdermal penetration of the pharmaco quinethaZone, quinidine, quinine, ranitidine, rauwolfia alka logically active agent or agents, minimize residence time of loids, riboflavin, rifampin, ritodrine, salicylates, scopola same on the skin and minimize untoward side effects. Those mine, secobarbital, Senna, Sannosides, simethicone, sodium results are obtained in part, by the hydrating effect of refined bicarbonate, sodium phosphate, Sodium fluoride, Spirono peanut oil on skin. lactone. Sucrulfate, Sulfacytine, Sulfamethoxazole, Sulfasala Zine, Sulfinpyrazone, Sulfisoxazole, Sulindac, talbutal, 0037. In the various embodiments, the compositions of tamazepam, terbutaline, terfenadine, terphinhydrate, teracy the invention are useful for application to any Subject in need clines, thiabendazole, thiamine, thioridazine, thiothixene, thereof. The subject can be any vertebrate, especially a thyroblobulin, thyroid, thyroxine, ticarcillin, timolol, tocain mammal, and most especially a human. The composition is ide, tolaZamide, tolbutamide, tolmetin, troZodone, , amenable to self-application. The amounts used are essen triamcinolone, trianterene, triazolam, trichlormethiazide, tri tially as known in the art, although amounts can be modified cyclic antidepressants, trifluoperazine, triflupromazine, tri based on empirical data and routine experimentation. hexyphenidyl, trimeprazine, trimethobenzamine, trimethop 0038. Other features, objects, and advantages of the rim, tripclennamine, triprolidine, Valproic acid, Verapamil invention will be apparent from the description and from the and Xanthine. claims. In the specification and the appended claims, the 0.031) Suitable keratolytic agents include salicylic acid, singular forms include plural references unless the context derivatives of salicylic acid such as 5-octanoyl salicylic acid, clearly dictates otherwise. Unless defined otherwise, all and resorcinol; such as retinoic acid and deriva technical and Scientific terms used herein have the same tives thereof (e.g., cis and trans); Sulfur-containing D and L meaning as commonly understood by one of ordinary skill amino acids and derivatives and salts thereof, particularly in the art to which this invention belongs. N-acetyl derivatives, such as N-acetyl-L-cysteine; lipoic 0.039 The following EXAMPLES are presented to more acid; antibiotics and antimicrobials such as benzoyl peroX fully illustrate the invention. The EXAMPLES should in no ide, actopiroX, , trichlorobanilide, azelaic acid, way be construed as limiting the scope of the invention, as phenoxyethanol, phenoxypropanol, phenoxyisopropanol, defined by the appended claims. ethyl acetate, clindamycin and meclocycliue; sebostats Such as flavonoids; and bile salts such as Scymnol sulfate and EXAMPLE 1. derivatives thereof, deoxycholate and cholate. Test of Hydrating Effects on Human Skin by 0032 Examples of antiwrinkle and antiskin atrophy Refined Peanut Oil actives that can be used in the topical preparations of interest include retinoic acid and derivatives; retinol; retinyl esters: 0040. A test was performed to determine whether pure salicylic acid and derivatives thereof. Sulfur-containing D peanut oil or a corticoid oil formulation and its components and L, amino acids and their derivatives and salts, particu could improve hydrating effects on human skin. The mea larly the N-acetyl derivatives, thiols, e.g. ethane thiol: alpha Suring was performed using biometric techniques. Transepi hydroxy acids, e.g. glycolic acid, and lactic acid; phytic acid, dermal water loss (TEWL) was used as a parameter of ; lysophosphatidic acid, and skin peel agents, e.g., monitoring the irritant response and capacitance as param phenol. eters of skin hydration. The side effects were also observed US 2007/O 140999 A1 Jun. 21, 2007 in the test. The testing was done by visual grading and by single application as compared to water or no treatment. bioengineering techniques on ten healthy Subjects (3 male There was no statistical difference between plain peanut oil, and 7 female, mean ages 45+9). The results showed that the moisturizing vehicle that contains peanut oil and the plain peanut oil, the corticoid oil formulation containing corticoid oil formulation that contains peanut oil. peanut oil and the moisturizing vehicle containing peanut oil significantly improve skin hydration after one application. 0049) No VS alternation was observed. 0041. Three parameters were selected to evaluate the 0050 Hydrated skins can increase the penetration of effects of test formulations: applied medicaments or active ingredients, such as fluoci nolone acetonide. 0.042 Clinical visual scoring (scaling, adverse effect-if any). EXAMPLE 2 0051 A cream was prepared with the following ingredi ents in the amounts indicated. Ole slight (weak spotty erythema) moderate erythema TABLE 1. severe erythema with edema or palpable infiltration 800 g Batch Ingredient Quantity Formula 0.043 Transepidermal water loss (TEWL) was assessed magnesium aluminum silicate NF 24 g 3.00% by a Tewameter (Tewameter TM 210, Courage, Cologne, butylated hydroxytoluene NF 320 mg O.04% cetyl alcohol NF 32 g 4.00% Germany, and Acaderm Inc., Menlo Park, Calif.). TEWL stearic acid NF 24 g 3.00% documents integrity of stratum corneum water barrier func stearyl alcohol NF 32 g 4.00% tion and is a sensitive indicator of skin water barrier alter methylparaben NF 1.440 g O.18% ation. The value of TEWL was expressed g/m per h. propylparaben NF 160 mg O.02% Arlacel (R) 165 glycerol 28 g 3.50% 0044 Skin hydration (i.e., electrical capacitance) was stearate and PEG-100 stearate measured by a Corneometer (CM 820, Courage & Khazaka, glycerol monostearate Cologne, Germany). Capacitance was expressed digitally in methyl gluceth-10 32 g 4.00% glycerin USP 24 g 3.00% arbitrary units (a.u.). isopropyl myristate 32 g 4.00% peanut oil NF refined 40 g S.00% 0045. The measurements were conducted in a room with tretinoin USP 400 mg O.05% daily ranges of relative humidity (RH) from 55.0+4.6% and fluocinolone acetonide USP 80 mg O.01% temperature from 18.4+0.5° C. The values (RH and C.) citric acid USP 400 mg O.05% were recorded daily. Each subject was rested at least 30 min hydroquinone USP 32 g 4.00% for acclimation before measurements. sodium metabisulfite NF 1.6 g. O.20% purified water USP 495.60 g 61.95% 0046 Basal values of TEWL and capacitance were mea Sured on each test site prior to treatment with test materials. Total 100.00% The flexor aspects of both forearms of subjects were used for testing. The test sites on the left and right forearm of each Subject were randomized. One test site served as normal skin 0052 Fluocinolone acetonide is a synthetic fluorinated control (without treatment). Other sites were wetted by corticosteroid for topical dermatological use and is classified spraying distilled water (approximately 0.1 ml) over a 3 cm therapeutically as an anti-inflammatory. It is a white crys skin Surface area. This saturation procedure was repeated on talline powder that is odorless and stable in light. The the same site each 5 minutes, for a total of 3 applications. chemical name for fluocinolone acetonide is (6,11,16)-6.9- Five minutes after the last application, 0.2 ml of a corticoid difluoro-11,21-dihydroxy-16,17-(1-methylethylidene)bi oil formulation (Derma-Smooth/FSR, Hill Dermaceuticals, S(oxy)-pregna-1,-4-diene-320-dione. The molecular for Sanford, Fla.), a moisturizing vehicle and plain peanut oil mula is CHFO and the molecular weight is 452.5. The were applied to the each pre-designated site (3 cm). One amount of fluocinolone acetonide in the composition of the site was kept blank as a control (water Saturation only). invention can be in an amount understood by those of skill Thirty minutes later, the test sites were gently wiped with in the art to be effective. In particular, the amount can be in paper tissues, and then clinical scores, TEWL, and capaci the range of between 0.005% and 0.02%. tance were recorded at each test site. These were repeated at 0053 Tretinoin is all-trans-retinoic acid formed from the 2 and 3 hours. oxidation of the aldehyde group of retinene to a carboxyl 0047 Statistics were performed using a computer pro group. It is highly reactive to light and moisture. Tretinoin gram SigmaStat(R) (SPSS Science, Chicago, Ill.). Values of is classified therapeutically as a keratolytic. The chemical TEWL and capacitance between blank plus water only site name for tretinoin is (all-E)-3,7-dimethyl-9-(2,6,6-trim and other test sites were analyzed with the paired t test. ethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid. The One-way repeated-measures ANOVA was utilized to evalu molecular formula is CHO and the molecular weight is ate the differences among the plain peanut oil, the corticoid 300.44. The amount of tretinoin in the composition of the oil formulation and the moisturizing vehicle-treated sites. invention can be in amount understood by those of skill in Levels of significance were marked as follows: *p-0.05, the art to be effective. In particular, the amount can be in the **p-0.01, ***p-0.001. range of between 2% and 10%. 0.048. The results showed that plain peanut oil signifi 0054 Hydroquinone is classified therapeutically as a cantly improved skin hydration after 30 minutes of each depigmenting agent. It is prepared from the reduction of US 2007/O 140999 A1 Jun. 21, 2007 p-benzoquinone with sodium bisulfite. It occurs as fine 0066. The resulting composition of the invention can be white needles that darken on exposure to air. The chemical stored at controlled room temperature of 68 to 77 F. (20-25° name for hydroquinone is 1,4-benzenediol. The molecular C.). formula is CHO, and the molecular weight is 110.11. The amount of hydroquinone in the composition of the invention EXAMPLE 3 can be in amount understood by those of skill in the art to be effective. In particular, the amount can be in the range of 0067. In another embodiment, the composition contains between 0.02% and 0.1%. tretinoin (0.05%) as the medicament in a cream base con 0.055 The method for making a therapeutic cream taining isopropyl myristate and refined peanut oil. This employs the following steps: embodiment is useful for the treatment of acne. 0056 To a 1000 ml beaker add: TABLE 2 800 g Batch Ingredient Quantity Formula Water 495.6 g. magnesium aluminum silicate NF 24.00 g 3.00% magnesium aluminum silicate NF 24 g butylated hydroxytoluene NF 1.60 mg O.20% butylated hydroxytoluene 0.32 g cetyl alcohol NF 32.00 g 4.00% stearic acid NF 24.00 g 3.00% stearyl alcohol NF 32.00 g 4.00% methylparaben NF 1.44 g O.18% 0057 Heat this mixture to 75-80° C. with continued propylparaben NF 0.16 g O.02% mixing. Arlacel (R) 165 glycerol 28.00 g 3.50% stearate and PEG-100 stearate 0.058 To a 400 ml beaker add: glycerol monostearate methyl gluceth-10 32.00 g 4.00% glycerin USP 24.00 g 3.00% isopropyl myristate 32.00 g 4.00% cetyl alcohol 32 g peanut oil NF refined 40.00 g S.00% Stearic acid 24 g tretinoin USP 0.40 g O.05% Stearyl alcohol 32 g citric acid USP anhydrous 0.40 g O.05% methyl glueth-10 32 g purified water USP 528.00 g 66.00% methylparaben 1.44 g propylparaben 0.16 g Total 100.00% glycerin 24 g isopropyl myristate 32 g peanut oil 40 g EXAMPLE 4 0059) Heat this mixture to 75-80° C. and mix until 0068. In another embodiment, the composition contains dissolved. hydroquinone (4.0%) as the medicament in a cream base containing isopropyl myristate and peanut oil. This embodi 0060. With good agitation transfer the mixture in the 400 ment is useful for the treatment of hyperpigmentation or ml beaker to the 1000 ml beaker. Allow cooling to begin. postinflammatory conditions. An embodiment is provided in TABLE 3.

TABLE 3 When the temperature reaches 70° C. add: 800 g Batch Arlace (R) 165 28 g Ingredient Quantity Formula tretinoin 0.4 g fluocinolone acetonide 0.08 g magnesium aluminum silicate NF 24.00 g 3.00% Continue mixing and cooling. butylated hydroxytoluene NF 0.320 g O.04% When the temperature reaches 60° C. add: cetyl alcohol NF 32.00 g 4.00% stearic acid NF 24.00 g 3.00% citric acid anhydrous 0.4 g stearyl alcohol NF 32.00 g 4.00% When the temperature reaches 55° C. add: methylparaben NF 1.44 g O.18% propylparaben NF 0.16 g O.02% hydroquinone 32 g Arlacel (R) 165 glycerol 28.00 g 3.50% Continue mixing and cooling. stearate and PEG-100 stearate glycerol monostearate and polyoxyethylene stearate methyl gluceth-10 32.00 g 4.00% 0061. When the temperature reaches 50° C., place the glycerin USP 24.00 g 3.00% beaker under a counter top homogenizer. Start the homog isopropyl myristate 32.00 g 4.00% enizer and continue mixing and cooling. peanut oil NF refined 40.00 g S.00% citric acid USP anhydrous 0.40 g O.05% 0062) When the temperature reaches 45° C. add: hydroquinone USP 32.00 g 4.00% sodium metabisulfite NF 1.60 g O.20% 0063 sodium metabisulfite 1.6 g. purified water USP 527.52 g 65.94% 0064 Continue mixing and cooling. Total 100.00% 0065 Mix the completed batch for at least 30 minutes. US 2007/O 140999 A1 Jun. 21, 2007

EXAMPLE 5 What is claimed is: 1. A medicament for use on keratinized skin comprising: 0069. In another embodiment, the composition contains (a) a vehicle comprising hydrophilic reagents and lipo fluocinolone acetonide (0.01%) as the medicament in a philic reagents, wherein said vehicle comprises refined cream base containing isopropyl myristate and refined pea peanut oil; and nut oil. This embodiment is useful for the treatment of (b) a pharmaceutically active agent. inflammatory conditions. An embodiment is provided in 2. The medicament of clan 1, wherein said refined peanut TABLE 4. oil is present in a range of between about 1% and about 10% by weight. TABLE 4 3. The medicament of claim 1, wherein said pharmaceu tically active agent is a corticosteroid, a keratolytic agent, a 800 g Batch Ingredient Quantity Formula depigmenting agent or a combination thereof. 4. The medicament of claim3, wherein said corticosteroid magnesium aluminum silicate NF 24.00 g 3.00% is fluocinolone. butylated hydroxytoluene NF 0.320 g O.04% 5. The medicament of claim 3, wherein said keratolytic cetyl alcohol NF 32.00 g 4.00% stearic acid NF 24.00 g 3.00% agent is tretinoin. stearyl alcohol NF 32.00 g 4.00% 6. The medicament of claim 3, wherein said depigmenting methylparaben NF 1.44 g O.18% agent is hydroquinone. propylparaben NF 0.16 g O.02% 7. The medicament of claim 3, wherein said pharmaceu Arlacel (R) 165 glycerol 28.00 g 3.50% tically active agent is a combination of fluocinolone, tretin stearate and PEG-100 stearate oin and hydroquinone. glycerol monostearate and polyoxyethylene stearate 8. The medicament of claim 1, wherein said pharmaceu methyl gluceth-10 32.00 g 4.00% tically active agent is fluorouracil. glycerin USP 24.00 g 3.00% 9. The medicament of claim 1, wherein said pharmaceu isopropyl myristate 32.00 g 4.00% tically active agent is betamethasone. peanut oil NF refined 40.00 g S.00% 10. A process of making a composition, comprising the citric acid USP anhydrous 0.40 g O.05% steps of fluocinolone acetonide USP 80.0 mg O.01% (a) combining water and at least one hydrophilic reagent Sodium metabisulfite NF 1.60 g O.20% purified water USP 528 g 66% to form an aqueous phase; (b) combining peanut oil with at least one other hydro Total 100.00% phobic compound to form a non-aqueous phase; (c) combining the aqueous phase and non-aqueous phase to form a biphasic mixture; 0070 The foregoing description has been presented only (d) adding at least one emulsifier, and for the purposes of illustration and is not intended to limit (e) homogenizing the mixture to form the composition. the invention to the precise form disclosed, but by the claims 11. The process of claim 10, wherein at least one medi appended hereto. cament is added during step (c) or (d). 0071 All patents and publications cited in this specifi 12. A composition made by the process of claim 9 or 10. cation are incorporated by reference herein in entirety. k k k k k