US 2008011.3037A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0113037 A1 Green et al. (43) Pub. Date: May 15, 2008

(54) TOPICAL COMPOSITIONS COMPRISING Publication Classification POLYHYDROXY ACIDS AND/OR LACTONES (51) Int. Cl. FOR IMPROVED CUTANEOUSEFFECTS OF A633/40 (2006.01) OXDATIVE THERAPEUTC DRUGS A6II 3/34 (2006.01) A63L/385 (2006.01) A633/04 (2006.01) (76) Inventors: Barbara A. Green, Edison, NJ A6II 47/12 (2006.01) (US); David J. Milora, Blue Bell, A6IP 700 (2006.01) PA (US) A6II 35/04 (2006.01) A633/22 (2006.01) Correspondence Address: A633/32 (2006.01) GOODWIN PROCTER LLP (52) U.S. Cl...... 424/616; 424/640; 424/660; 424/667; 901 NEW YORKAVENUE, N.W. 424/703; 424/725.1: 514/18: 514/356; 514/440; WASHINGTON, DC 20001 514/460, 514/714: 514/785 (57) ABSTRACT (21) Appl. No.: 11/682,039 Embodiments relate generally to topical compositions useful for treating or preventing a variety of cosmetic conditions and dermatological disorders, where the composition comprises an oxidative pharmaceutical drug and an antioxidant polyhy (22) Filed: Mar. 5, 2007 droxy acid or polyhydroxylactone. The polyhydroxy acid or polyhydroxy lactone improves the cutaneous effects of the Related U.S. Application Data drug. The embodiments further relate to the treatment of a variety of cosmetic conditions and dermatological disorders (60) Provisional application No. 60/865.244, filed on Nov. comprising administering to a subject an effective amount of 10, 2006. the composition and to methods of making the compositions. US 2008/O 113037 A1 May 15, 2008

TOPCAL COMPOSITIONS COMPRISING is a method of making a composition for topical administra POLYHYDROXY ACDS AND/OR LACTONES tion that can be useful for treating a variety of cosmetic FOR IMPROVED CUTANEOUSEFFECTS OF conditions and dermatological disorders, where the compo OXDATIVE THERAPEUTIC DRUGS sition comprises an oxidative pharmaceutical drug and a polyhydroxy acid or polyhydroxy lactone. CROSS-REFERENCE TO RELATED APPLICATION DETAILED DESCRIPTION OF THE PREFERRED 0001. This application claims benefit of U.S. Provisional EMBODIMENTS Application No. 60/865,244, filed on Nov. 10, 2006, which is 0008. The terminology used herein is for the purpose of hereby incorporated by reference in its entirety. describing particular embodiments only, and is not intended to limit the scope of the present invention. As used throughout FIELD OF THE INVENTION this disclosure, the singular forms “a,” “an and “the include 0002 Embodiments relate generally to topical composi plural references unless the context clearly dictates other tions useful for treating or preventing a variety of cosmetic wise. conditions and dermatological disorders, where the compo 0009. Oxidative pharmaceutical drugs can be chemical sition comprises an oxidative pharmaceutical drug and a compounds that contain at least one oxidative functional polyhydroxy acid or polyhydroxy lactone. The polyhydroxy group or that function as oxidative Substances when topically acid or polyhydroxy lactone improves the cutaneous effects applied to the cutaneous tissue. Such as peroxide, peracid, of the drug. The embodiments further relate to the treatment Superoxide and the like. Examples of Such drugs are benzoyl of variety of cosmetic conditions and dermatological disor peroxide, carbamide peroxide, coal tar, glutathione, hydro ders comprising administering to a Subject an effective gen peroxide, iodine, juniper tar, lipoic acid, NAD", amount of the composition and to methods of making the NADP", nitrogen oxide, oxygen, pine tar, potassium per compositions. manganate, povidone-iodine, perbenzoic acid, Sulfur, Sulfur dioxide, Sodium borate, Sodium perborate, shale tar, DESCRIPTION OF RELATED ART ubiquinone and wood tar. 0010 When an oxidative pharmaceutical drug is adminis 0003 Oxidative pharmaceutical drugs can be chemical tered to cutaneous tissues including the skin for topical treat compounds that contain at least one oxidative functional ment, adverse reactions occur. The adverse reactions to the group or that function as oxidative substances when topically skin include (a) dryness, (b) irritation, (c) erythema, (d) dam applied to the skin, such as peroxide, peracid, Superoxide and age and (e) other miscellaneous side effects. These adverse the like. Examples of such drugs are benzoyl peroxide, hydro reactions are not required for or are unrelated to the therapeu gen peroxide and perbenzoic acid. tic effects of the drug. The present inventors have discovered 0004. When an oxidative pharmaceutical drug is adminis that when a polyhydroxy acid or polyhydroxy lactone is tered to cutaneous tissues including the skin for topical treat incorporated into a composition comprising the oxidative ment of dermatological disorders, the adverse reactions to the pharmaceutical drug, the adverse reactions to the skin by the skin include (a) dryness, (b) irritation, (c) erythema, (d) dam drug are eliminated or minimized, and therapeutic efficacy is age and (e) other miscellaneous side effects. Such adverse maintained or enhanced. reactions and damages to the skin are not required for or are 0011. As an illustration, when a composition containing unrelated to the therapeutic effects of the drug. oxidative benzoyl peroxide is administered for topical treat 0005 U.S. Pat. No. 6,036,963 discloses the use of glu ment of acne, the skin becomes dry, erythematous and irri conolactone or glucarolactone in cosmetic skin care compo tated. Many subjects discontinue the use of Such composi sitions as an anti-irritant. The gluconolactone or glucarolac tions because of the adverse skin reactions. When a tone are said to alleviate or control any skin irritation that may composition comprising gluconolactone and oxidative ben be caused by glycolic acid. Zoyl peroxide is administered topically, however, there is less, or even no irritation, and the acne lesions are improved. SUMMARY OF INVENTION 0012 Polyhydroxy acids and polyhydroxy lactones pref 0006. It is desirable to minimize or eliminate the adverse erably are (a) modulators for skin keratinization, (b) antioxi reactions and damages to the skin caused by oxidative phar dant compounds, (c) preventive or counter-irritants, (d) mois maceutical drugs. These adverse reactions are not required turizers, (e) skin barrier strengtheners, (f) restorers when for or are unrelated to the therapeutic effects of the drug. The topically administered to cutaneous tissues; and (g) anti-ag present inventors have discovered that when a polyhydroxy ing compounds by increasing dermal biosynthesis. Polyhy acid or polyhydroxy lactone is incorporated into a composi droxy acids and polyhydroxy lactones typically are organic tion comprising the oxidative pharmaceutical drug, the carboxylic compounds having at least two hydroxyl groups in adverse reactions to the skin by the drugs are eliminated or the molecules and with preferred molecular weight of minimized. between about 100 and about 300. These polyhydroxy acids 0007. One embodiment of this invention is a composition and polyhydroxylactones include gluconic acid, gluconolac for topical administration comprising an oxidative pharma tone, ribonic acid, ribonolactone, galactonic acid, galactono ceutical drug and a polyhydroxy acid or polyhydroxylactone. lactone, glucoheptonic acid, glucoheptonolactone, glucu Another embodiment of this invention is a method of topical ronic acid, glucuronolactone, galacturonic acid, cutaneous treatment of a variety of cosmetic conditions and galacturonolactone, glucaric acid, glucarolactone, galactaric dermatological disorders comprising administering to a Sub acid and galactarolactone. ject an effective amount of a composition comprising an 0013 The polyhydroxyacids and polyhydroxylactones of oxidative pharmaceutical drug and a polyhydroxy acid or the present embodiments can be divided into the following polyhydroxy lactone. Another embodiment of this invention three groups. US 2008/O 113037 A1 May 15, 2008

0014 (A) Aldonic Acids and Aldonolactones idoheptaric acid and idoheptarolactone, galactoheptaric acid 0015. When a common carbohydrate, also called aldose, is and galactoheptarolactone, taloheptaric acid and taloheptaro oxidized at the carbon one position from an aldehyde to a lactone). carboxyl group, the product is called aldonic acid. For 0020 (C) Alduronic Acids and Alduronolactones. example, when glucose is oxidized at the carbon one position, 0021 Alduronic acid is typically obtained from a carbo the product is gluconic acid. The aldonic acid usually has hydrate, aldose, by oxidation of the terminal carbon to car multiple hydroxyl groups. The generic structure can be boxyl group, and the carbon one position remains as aldehyde shown as follows: group, Such as glucuronic acid from glucose. Similar to aldonic acid and aldaric acid, alduronic acid also has multiple R(CHOH),CHOHCOOH hydroxyl groups attached to the carbon chain between two where R is usually Horan alkyl group and n is an integer from functional groups, one aldehyde and one carboxyl groups in 1-9. The aldonic acids can exist as stereoisomers as D. L. and this case. Many alduronic acids exist as intramolecular lac DL or R,S and RS forms. Many aldonic acids form intramo tones, alduronolactones. Such as glucuronolactone from glu lecular lactones, aldonolactones, by removing one mole of curonic acid. The generic structure can be shown as follows: water between the carboxyl group and one hydroxyl group. HOOC(CHOH),CHOHCHO 0016. The following are representative aldonic acids and where n is an integer from 1-9. The alduronic acids can exist aldonolactones: 2,3-dihydroxypropanoic acid (glyceric as stereoisomers as D. L. and DL or R, S and RS forms. acid); 2.3,4-trihydroxybutanoic acids (stereoisomers; eryth 0022. The following are representative alduronic acids ronic acid and erythronolactone, threonic acid and threono and alduronolactones: erythruronic acid and threuronic acid, lactone); 2.3.4.5-tetrahydroxypentanoic acids (stereoiso riburonic acid and riburonolactone, araburonic acid and mers; ribonic acid and ribonolactone, arabinoic acid and araburonolactone, Xyluronic acid and Xyluronolactone, lyXu arabinolactone, Xylonic acid and Xylonolactone, lyxonic acid ronic acid and lyXuronolactone, alluronic acid and allurono and lyxonolactone); 2,3,4,5,6-pentahydroxyhexanoic acids lactone, altruronic acid and altruronolactone, glucuronic acid (stercoisomers; allonic acid and allonolactone, altronic acid and glucuronolactone, mannuronic acid and mannuronolac and altronolactone, gluconic acid and gluconolactone, man tone, guluronic acid and guluronolactone, iduronic acid and noic acid and mannolactone, gulonic acid and gulonolactone, iduronolactone, galacturonic acid and galacturonolactone, idonic acid and idonolactone, galactonic acid and galactono taluronic acid and taluronolactone, allohepturonic acid and lactone, talonic acid and talonolactone); 2.3.4.5,6,7-hexahy allohepturonolactone, altrohepturonic acid and altroheptur droxyheptanoic acids (Stereoisomers; alloheptonic acid and onolactone, glucohepturonic acid and glucohepturonolac alloheptonolactone, altroheptonic acid and altroheptonolac tone, mannohepturonic acid and mannohepturonolactone, tone, glucoheptonic acid and glucoheptonolactone, manno gulohepturonic acid and gulohepturonolactone, idoheptur heptonic acid and mannoheptonolactone, guloheptonic acid onic acid and idohepturonolactone, galactohepturonic acid and guloheptonolactone, idoheptonic acid and idoheptono and galactohepturonolactone, talohepturonic acid and talo lactone, galactoheptonic acid and galactoheptonolactone, hepturonolactone. taloheptonic acid and taloheptonolactone). 0023 The compositions of the present embodiments also 0017 (B) Aldaric Acids and Aldarolactones. may contain other pharmaceutical or topical agents for Syn 0018. The aldaric acid typically has multiple hydroxyl ergetic or synergistic effects. The pharmaceutical and other groups attached to the carbon chain Surrounded by two car topical agents which can be incorporated into the composi boxyl groups. Many aldaric acids form intramolecular lac tions include those that improve or eradicate age spots, kera tones, aldarolactones, by removing one mole of water toses and wrinkles; local analgesics and anesthetics; antiacne between one of the two carboxyl groups and one hydroxyl agents; antibacterials; antiyeast agents; antifungal agents; group, Such as glucarolactone from glucaric acid. The generic antiviral agents; antidandruff agents; antidermatitis agents; structure can be shown as follows: antihistamine agents; antipruritic agents; antiemetics; antimotionsickness agents; anfiinflammatory agents; antihy HOOC(CHOH),CHOHCOOH perkeratolytic agents; antiperspirants; antipsoriatic agents; where n is an integer from 1-9. The aldaric acids can exist as antiseborrheic agents; hair conditioners and hair treatment stereoisomers as D. L. and DL or R,S and RS forms. agents; antiaging and antiwrinkle agents; Sunblock and Sun 0019. The following are representative aldaric acids and Screen agents, skin lightening agents; depigmenting agents: aldarolactones: 2,3-dihydroxybutane-1,4-dioic acids (stere Vitamins; corticosteroids; tanning agents; humectants; hor oisomers; erythraric acid and threaric acid); 2.3,4-trihydroxy mones; retinoids; gum disease or oral care agents; topical pentane-1,5-dioic acids (stereoisomers; ribaric acid and rib cardiovascular agents; corn, callus and wart removing agents; arolactone, arabaric acid and arabarolactone, Xylaric acid and and depilating agents. Xylarolactone, lyXaric acid and lyXarolactone); 2.3.4.5-tet 0024 Examples of the above agents include abacavir, ace rahydroxyhexane-1,6-dioic acids (stereoisomers; allaric acid butolol, acetaminophen, acetaminosalol, acetazolamide, and allarolactone, altraric acid and altrarolactone, glucaric acetohydroxamic acid, acetylsalicylic acid, acitretin, aclo acid and glucarolactone, mannaric acid and mannarolactone, Vate, acrivastine, actiq, acyclovir, adapalene, adefovir dipiv gularic acid and gularolactone, idaric acid and idarolactone, oxil, adenosine, albuterol, alfuZosin, allopurinol, alloxan galactaric acid and galactarolactone, talaric acid and talaro thine, almotriptan, alprazolam, alprenolol, aluminum acetate, lactone); 2.3.4.5,6-pentahydroxyheptane-1,7-dioic acids aluminum chloride, aluminum chlorohydroxide, aluminum (stereoisomers; alloheptaric acid and alloheptarolactone, hydroxide, amantadine, amiloride, aminacrine, aminoben altroheptaric acid and altroheptarolactone, glucoheptaric acid Zoic acid (PABA), aminocaproic acid, aminosalicylic acid, and glucoheptarolactone, mannoheptaric acid and manno amiodarone, amitriptyline, amlodipine, amocarzine, amodi heptarolactone, guloheptaric acid and guloheptarolactone, aquin, amorolfine, amoxapine, amphetamine, amplicillin, US 2008/O 113037 A1 May 15, 2008 anagrelide, anastroZole, anthralin, apomorphine, aprepitant, date, methyl salicylate, metiamide, metolaZone, metoprolol. arbutin, aripiprazole, ascorbic acid, ascorbyl palmitate, ata metronidazole, mexiletine, miconazole, midazolam, mido Zanavir, atenolol, atomoxetine, atropine, azathioprine, aze drine, miglustat, minocycline, minoxidil, mirtazapine, mitox laic acid, azelastine, azithiromycin, bacitracin, beclometha antrone, moexiprilat, molindone, monobenzone, morphine, SO dipropionate, bemegride, benazepril, moxifloxacin, moXonidine, mupirocin, nadolol, naftifine, bendroflumethiazide, benzocaine, benzonatate, benzophe nalbuphine, nalmefene, naloxone, naproxen, nefazodone, none, benztropine, bepridil, betamethasone dipropionate, nelfinavir, neomycin, nevirapine, nicardipine, nicotine, nife betamethasone Valerate, brimonidine, brompheniramine, dipine, nimodipine, nisoldipine, nizatidine, norepinephrine, bupivacaine, buprenorphine, bupropion, burimamide, buten nystatin, octopamine, octreotide, octyl methoxycinnamate, afine, butoconazole, cabergoline, caffeic acid, caffeine, cal octyl salicylate, ofloxacin, olanzapine, olmesartan medox cipotriene, camphor, candesartan cilexetil, capsaicin, car omil, olopatadine, omeprazole, ondansetron, oxiconazole, bamazepine, cefditoren pivoxil, cefepime, cefpodoxime oxotremorine, oxybenzone, oxybutynin, oxycodone, proxetil, celecoxib, cetirizine, cevimeline, chitosan, chlor oxymetazoline, padimate O, palonosetron, pantothenic acid, diazepoxide, chlorhexidine, chloroquine, chlorothiazide, pantoyl lactone, paroxetine, pemoline, penciclovir, penicil chloroxylenol, chlorpheniramine, chlorpromazine, chlorpro lamine, penicillins, pentazocine, pentobarbital, pentostatin, pamide, ciclopiroX, ciloStaZol, cimetidine, cinacalcet, cipro pentoxifylline, pergolide, perindopril, permethrin, phencyc floxacin, citalopram, citric acid, cladribine, clarithromycin, lidine, phenelzine, pheniramine, phenmetrazine, phenobar clemastine, clindamycin, clioquinol, clobetasol propionate, bital, phenol, phenoxybenzamine, phentolamine, phenyleph clomiphene, clonidine, clopidogrel, clotrimazole, clozapine, rine, phenylpropanolarnine, phenytoin, physostigmine, cocaine, codeine, cromolyn, crotamiton, cyclizine, cycloben pilocarpine, pimozide, pindolol, pioglitaZone, pipamazine, Zaprine, cycloserine, cytarabine, dacarbazine, dalfopristin, piperonyl butoxide, pirenzepine, podofilox, podophyllin, dapsone, daptomycin, daunorubicin, deferoxamine, dehy pratipexole, pramoxine, prazosin, prednisone, prenalterol, droepiandrosterone, delavirdine, desipramine, desloratadine, prilocaine, procainamide, procaine, procarbazine, pro desmopressin, desoximetasone, dexamethasone, dexmedeto mazine, promethazine, promethazine propionate, pro midine, dexmethylphenidate, dexraZoxane, dextroamphet pafenone, propoxyphene, propranolol, propylthiouracil, pro amine, diazepam, dicyclomine, didanosine, dihydrocodeine, triptyline, pseudoephedrine, pyrethrin, pyrilamine, dihydromorphine, diltiazem, 6,8-dimercaptooctanoic acid pyrimethamine, quetiapine, quinapril, quinethaZone, quini (dihydrolipoic acid), diphenhydramine, diphenoxylate, dipy dine, quinupristin, rabeprazole, reserpine, resorcinol, retinal, ridamole, disopyramide, dobutamine, dofetilide, dolasetron, 13-cis retinoic acid, retinoic acid, retinol, retinyl acetate, donepezil, dopa esters, dopamnide, dopamine, dorzolamide, retinyl palmitate, ribavirin, ribonic acid, ribonolactone, doxepin, doxorubicin, doxycycline, doxylamine, doxypin, rifampin, rifapentine, rifaximin, riluzole, rimantadine, dulloxetine, dyclonine, econazole, eflornithine, eletriptan, risedronic acid, risperidone, ritodrine, rivastigmine, rizatrip emitricitabine, enalapril, ephedrine, epinephrine, epinine, epi tan, ropinirole, ropivacaine, salicylamide, Salicylic acid, sal rubicin, eptifibatide, ergotarnine, erythromycin, escitalo meterol, Scopolamine, selegiline, selenium sulfide, serotonin, pram, esmolol, esomeprazole, estazolam, estradiol. sertindole, Sertraline, Sibutramine, sildenafil. Sotalol, Strepto ethacrynic acid, ethinyl estradiol, etidocaine, etomidate, fam mycin, Strychnine, Sulconazole, Sulfabenz, Sulfabenzamide, ciclovir, famotidine, felodipine, fentanyl, ferulic acid, fex Sulfabromomethazine, Sulfacetamide, Sulfachlorpyridazine, ofenadine, flecainide, fluconazole, flucytosiine, fluocinolone Sulfacytine, Sulfadiazine, Sulfadimethoxine, Sulfadoxine, Sul acetonide, fluocinonide, 5-fluorouracil, fluoxetine, fluphena faguanole, Sulfalene, Sulfamethizole, Sulfamethoxazole, Sul Zine, flurazepam, fluvoxamine, formoterol, furosemide, fanilamide, Sulfapyrazine, Sulfapyridine, Sulfasalazine, Sulfa galactarolactone, galactonic acid, galactonolactone, galan Somizole, Sulfathiazole, Sulfisoxazole, tadalafil. tamsulosin, tamine, gatifloxacin, gefitinib, gemcitabine, gemifloxacin, tartaric acid, tazarotene, tegaserol, tellithromycin, telmisar glycolic acid, griseofulvin, guaifenesin, guanethidine, tan, temozolomide, tenofovir disoproxil, teraZosin, terbin N-guanylhistamine, haloperidol, haloprogin, hexylresorci afine, terbutaline, terconazole, terfenadine, tetracaine, tetra nol, homatropine, homosalate, hydralazine, hydrochlorothi cycline, tetrahydrozoline, theobromine, theophylline, azide, hydrocortisone, hydrocortisone 21-acetate, hydrocor thiabendazole, thioridazine, thiothixene, thymol, tiagabine, tisone 17-butyrate, hydrocortisone 17-valerate, timolol, tinidazole, tioconazole, tirofiban, tizanidine, tobra hydromorphone, hydroquinone, hydroquinone monoether, mycin, tocainide, tolaZoline, tolbutamide, tolnaftate, toltero hydroxy Zine, hyoscyamine, hypoxanthine, ibuprofen, ich dine, tramadol, tranylcypromine, traZodone, triarncinolone thammol. idarubicin, imatinib, imipramine, imiquimod, indi acetonide, triamcinolone diacetate, triamcinolone hexac navir, indomethacin, irbesartan, irinotecan, isoetharine, iso etonide, triamterene, triazolam, triclosan, triflupromazine, proterenol, itraconazole, kanamycin, ketamine, ketanserin, trimethoprim, trimipramine, tripelennamine, triprolidine, ketoconazole, ketoprofen, ketotifen, kojic acid, labetalol, lac tromethamine, tropic acid, tyramine, undecylenic acid, urea, tic acid, lactobionic acid, lamivudine, lamotrigine, lanSopra urocanic acid, ursodiol, Vardenafil. Venlafaxine, Verapamil, Zole, letrozole, leuprolide, levalbuterol, levofloxacin, Vitamin E acetate, Voriconazole, warfarin, Xanthine, lidocaine, lineZolid, lobeline, loperamide, losartan, loxapine, Zafirlukast, Zaleplon, Zinc pyrithione, Ziprasidone, Zolmitrip lysergic diethylamide, mafenide, malic acid, maltobionic tan and Zolpidem. acid, mandelic acid, maprotiline, mebendazole, mecamy 0025. In accordance to one embodiment of this invention, lamine, meclizine, meclocycline, memantine, menthol, mep compositions comprising an oxidative pharmaceutical drug eridine, mepivacaine, mercaptopurine, mescaline, metaneph and a polyhydroxy acid or polyhydroxylactone, can be useful rine, metaproterenol, metaraminol, metformin, methadone, for treating a variety of cosmetic conditions. Such cosmetic methamphetamine, methotrexate, methoxamine, methyldopa conditions or dermatological disorders include disturbed esters, methyldopamide, 3.4-methylenedioxymethamphet keratinization, defective syntheses of dermal components, amine, methylactic acid, methyl nicotinate, methylpheni and changes associated with aging of skin, nail and hair, and US 2008/O 113037 A1 May 15, 2008

those indications which include dryness or loose of skin, nail 0028. In accordance with an embodiment of the invention, and hair, Xerosis; ichthyosis; palmar and plantar hyperkera there is provided a method of making a composition for toses; uneven and rough Surface of skin, nail and hair, dan topical administration comprising an oxidative pharmaceuti druff Darier's disease; lichen simplex chronicus; keratoses; cal drug and a polyhydroxy acid or polyhydroxy lactone. A acne; pseudofolliculitis barbac, eczema, psoriasis; itchy Scalp Solution comprising the polyhydroxy acid or polyhydroxy and skin; pruritus; warts; herpes; age spots; lentigines; melas lactone is prepared, preferably with mixing and heating. mas; blemished skin; hyperkeratoses; hyperpigmented skin; Water soluble oxidative pharmaceutical drugs can be pre pared in Solution. An example of an insoluble oxidative phar abnormal or diminished syntheses of collagen, glycosami maceutical drug, specifically benzoyl peroxide, is prepared noglycans, proteoglycans and elastin as well as diminished using a dispersion of the oxidative pharmaceutical drug as levels of such components in the dermis; stretch marks; skin described herein. The particle size of the oxidative pharma lines; fine lines; wrinkles; thinning of skin, nail plate and hair, ceutical drug is reduced to an appropriate distribution where skin thickening due to elastosis of photoaging, loss or reduc the dispersion contains minimal grittiness and minimal dis tion of skin, nail and hair resiliency, elasticity and recoilabil cernable feel when applied to the skin. This is achieved by wet ity; lack of skin, nail and hair lubricants and luster, dull and milling, roller milling, crushing, or other typical methods of older-looking skin, nail and hair; and fragility and splitting of reducing particle sizes. The Solution comprising the polyhy nail and hair. droxy acid or polyhydroxy lactone is mixed with the oxida 0026. The concentration of an oxidative pharmaceutical tive pharmaceutical drug dispersion. If the solution compris drug in a composition where the composition comprises an ing the polyhydroxy acid or polyhydroxy lactone was oxidative pharmaceutical drug and a polyhydroxy acid or previously heated, it is first cooled prior to mixing with the polyhydroxy lactone, preferably is a concentration Sufficient oxidative pharmaceutical drug dispersion. to provide the desired cosmetic or dermatological effect, 0029. To prepare a topical combination composition for which may vary depending on the desired cosmetic condition synergetic or synergistic effects, an additional pharmaceuti or dermatological disorder being treated, the size of the cal or topical agent is incorporated into the above composi patient, and other factors. Preferably, the concentration of the tions by dissolving or mixing the agent into the formulation. oxidative pharmaceutical drug ranges from about 0.01% to 0030 The following are illustrative examples of formula about 99.9% by weight, based on the total weight of the tions and other aspects of the present embodiments. Although composition, more preferably from about 0.1% to about 50% the examples utilize only selected compounds and formula by weight, based on the total weight of the composition, and tions, it should be understood that the following examples are most preferably from about 0.5% to 25% by weight, based on illustrative and not limiting. the total weight of the composition. Those skilled in the art are capable of determining a Suitable concentration of oxidative EXAMPLE 1. pharmaceutical drug, using the guidelines provided herein. 0027. The concentration of a polyhydroxy acid or polyhy Benzoyl Peroxide Cream Containing Gluconolactone droxylactone where the composition comprises an oxidative 0031. The following is an example of the preparation of a pharmaceutical drug and a polyhydroxy acid or polyhydroxy benzoyl peroxide cream containing the polyhydroxylactone, lactone, preferably is a concentration sufficient to provide the Gluconolactone, for improved cutaneous effects. This formu desired cosmetic or dermatological effect, which may vary lation yields, but is not limited to, a cream containing 10% depending on the desired cosmetic condition or dermatologi benzoyl peroxide and 10% gluconolactone (which is subse cal disorder being treated, the extent and type of deleterious quently hydrolyzed to gluconic acid during preparation). effects from the drug on the skin, and other factors. Clinical Other formulation percentages of both benzoyl peroxide and benefits achieved by including a polyhydroxy acid or poly gluconolactone may be employed as desired. hydroxy lactone in combination with an oxidizing drug will 0032. Ingredients: vary depending on the nature and concentration of the oxi dizing drug, as well as the formulation vehicle. It is possible to eliminate or minimize the adverse reactions on skin by the oxidative drug and maintain or enhance therapeutic efficacy ngredients 9% WW of the oxidative drug using a low, middle or high concentra PartA Purified Water 28.00 tion of polyhydroxy acid and/or polyhydroxy lactone in an Magnesium Aluminum Silicate 1.OO acceptable vehicle. Careful selection of vehicle components Glycerin 2.OO along with clinical screening can be used to determine the Xanthan Gum 0.75 Part B Purified Water 2O.OO ideal combination of oxidative drug and polyhydroxy acid Gluconolactone 1O.OO and/or polyhydroxy lactone. Those skilled in the art are Strong Ammonia Solution To desired pH capable of determining the appropriate combinations of com Part C Cetyl Alcohol 1.OO ponents, and amounts, using the guidelines provided herein. Dimethicone 1.OO Preferably, the concentration of the polyhydroxyacid or poly Glyceryl Stearate 2.85 PEG-100 Stearate 1.25 hydroxylactone ranges from about 0.01% to about 99.9% by PEG-40 Stearate 2.OO weight, based on the total weight of the composition, more Part D Purified Water 13.00 preferably from about 0.1% to about 50% by weight, based on 75% Benzoyl Peroxide 13.33 the total weight of the composition, and most preferably from Sodium Dioctylsodiumsulfosuccinate O.O6 Enhancement Defoaming Agent QS about 0.5% to 25% by weight, based on the total weight of the Additives Preservative QS composition. Those skilled in the art are capable of determin Purified Water QS to 100% ing a suitable concentration of polyhydroxy acid or polyhy droxy lactone, using the guidelines provided herein. US 2008/O 113037 A1 May 15, 2008

0033. Typical Preparation Method: Prepare Part A by add 0036 Typical Preparation Method: See example 1 for a ing water and Magnesium Aluminum Silicate to the main typical preparation method. vessel with mixing. Add a premixed mixture of Xantham Gum and Glycerin to the mixture already in the main vessel. EXAMPLE 3 Prepare Part B in a separate vessel by adding water and Benzoyl Peroxide Creamy Cleanser Containing Glu Gluconolactone with continuous mixing. Continue mixing conolactone for a minimum of 2 hours to effect complete hydrolysis of the 0037. The following is an example of the preparation of a gluconolactone to gluconic acid. After the appropriate mixing benzoyl peroxide creamy cleanser containing the polyhy time, adjust pH with Ammonium Hydroxide solution (or droxy lactone, Gluconolactone, for improved cutaneous other suitable alkali) to the desired amount of free acid and effects. This formulation yields, but is not limited to, a creamy pH. Add Part B to Part A and heat the Part AB mixture to cleanser containing 7.5% benzoyl peroxide and 10% glu 70-75° C. Prepare Part C in a separate vessel by adding all conotactone. Other formulation percentages of both benzoyl the ingredients of Part C and heat to 70-75° C. Start continu peroxide and gluconolactone may be employed as desired. ous mixing when the solid material begins to melt. In a 0038 Ingredients: separate vessel prepare Part D. Reduce the particle size of the Benzoyl Peroxide dispersion to an appropriate distribution where the dispersion contains minimal grittiness when applied to the skin. This is achieved by any of the typical Ingredients 9% WW methods such as wet milling, roller milling, or crushing to PartA Purified Water 2S.OO achieve minimal discernable feel on the skin. Prepare the Gluconolactone 1O.OO emulsion by adding and mixing continuously the Part C mix Strong Ammonia Solution To desired pH Glycerin 1.OO ture to the Part AB mixture when all the mixtures are at Xanthan Gum O.25 70°-75° C., Cool the emulsion to below 40° C. and add the Magnesium Aluminum Silicate O.45 Part D Benzoyl Peroxide dispersion with continuous mixing. Cetyl Alcohol 6.OO Homogenize the mixture if desired. Add the remaining Cocoamidopropyl Betaine 8.OO Cetearyl Alcohol 1.OO optional ingredients and Sufficient water to replace losses Part B Purified Water 27.00 incurred during preparation. 75% Benzoyl Peroxide 13.33 Cetyl Alcohol 1.OO 75% Benzoyl Peroxide 13.33 EXAMPLE 2 Sodium Dioctylsodiumsulfosuccinate O.O6 Enhancement Defoaming Agent QS Benzoyl Peroxide Low Viscosity Fluid Containing Additives Preservative QS Gluconolactone Purified Water QS to 100% 0034. The following is an example of the preparation of a 0039 Typical Preparation Method: Prepare Part A by dis benzoyl peroxide low viscosity fluid, typically used for appli Solving gluconolactone in water. When dissolved, add a por cation from a pad, Swab, dauber, or other similar device. This tion of the Cocoamidopropyl Betaine and mix for approxi formulation contains the polyhydroxy lactone, Gluconolac mately 2 hours. Adjust to desired pH and add the Magnesium tone, for improved cutaneous effects. This formulation yields, Aluminum Silicate. Premix the Xanthan Gum with the Glyc but is not limited to, a low viscosity fluid containing 7.5% erin and add to the previous mixture. Heat to 60°-70°C. Add benzoyl peroxide and 10% gluconolactone (which is subse the remaining Part A ingredients and heat to 70°-75° C. form quently hydrolyzed to gluconic acid during preparation). ing a smooth mixture with all the Solid ingredients melted. Other formulation percentages of both benzoyl peroxide and Cool the emulsion to below 40°C. and add the Part B Benzoyl Gluconolactone may be employed as desired. Peroxide dispersion with continuous mixing. Homogenize if 0035) Ingredients: desired. Add the remaining optional ingredients and Sufficient water to replace any losses incurred during preparation. 0040 STABILITY DATA: An analysis of the stability of the compositions in examples 1-4 using HPLC yielded the ngredients 9% WW following results. PartA Purified Water 18.00 0041) Stability Data of Examples 1-3 Magnesium Aluminum Silicate 1.OO Glycerin S.OO Xanthan Gum O.15 Part B Purified Water 2O.OO % Benzoyl Peroxide Analyzed by HPLC Gluconolactone 1O.OO Strong Ammonia Solution To desired pH Initial 4-Weeks 8-Weeks 13-Weeks Part C Cetyl Alcohol O.SO Dimethicone 3.00 Example 1 Steareth-20 2.31 Steareth-2 O.68 25o C. 10.0% 9.5% 9.6% 9.6% Part D Purified Water 27.00 30° C. 10.0% 9.4% 9.4% 9.6% 75% Benzoyl Peroxide 1O.OO 40° C. 10.0% 9.4% 9.3% 9.3% Cetyl Alcohol 0.75 Example 2 Enhancement Defoaming Agent QS Additives Preservative QS 25o C. 7.70% 7.8% 7.9% 7.8% Purified Water QS to 100% 30° C. 7.70% 7.8% 7.8% 7.8% 40° C. 7.70% 7.70% 7.59% 7.1% US 2008/O 113037 A1 May 15, 2008

Sulfate irritant control. Accordingly, polyhydroxy acids and -continued polyhydroxy bionic acids by themselves are not irritating compounds, although prior to the present disclosure, it was % Benzoyl Peroxide Analyzed by HPLC not known that these compounds could reduce the irritating Initial 4-Weeks 8-Weeks 13-Weeks effects and potential of oxidative drugs. Example 3 EXAMPLE 6 25o C. 7.70% 7.8% 7.8% 30° C. 7.70% 7.8% 7.9% Benzoyl Peroxide--Polyhydroxy Acid Cleanser 40° C. 7.70% 7.9% 7.0% Evaluation 0046. In order to determine whether the addition of poly EXAMPLE 4 hydroxy acid in the composition couldenhance aesthetics and tolerability of a formulation containing oxidizing agents, a Benzoyl Peroxide Invert Gel Containing Gluconolac panel of twelve volunteers compared two test wash-off tOne cleanser formulations. The first formulation contained 7.5% 0042. The following is an example of the preparation of a by weight benzoyl peroxide plus 4% gluconolactone, and the benzoyl peroxide invert gel containing the polyhydroxy lac second formulation contained 7.5% by weight benzoyl per tone, Gluconolactone, for improved cutaneous effects. This oxide plus 10% gluconolactone. After using the cleansers for formulation yields, but is not limited to, a water-in-silicone a controlled period of time, the formulation containing ben gel containing 10% benzoyl peroxide and 5% gluconolactone Zoyl peroxide plus 10% gluconolactone was preferred over (which is Subsequently hydrolyzed to gluconic acid during the formulation containing 4% gluconolactone because it preparation). Other formulation percentages of both benzoyl more effectively removed dirt and oil, and did not cause as peroxide and gluconolactone may be employed as desired. much erythema as the 4% formulation. Nearly 80% of the 0043 Ingredients: panel selected the 10% gluconolactone-containing formula tion in a forced preference test. The results of this direct comparison demonstrate the utility of including a polyhy droxyacid in a wash-off formulation containing the oxidizing Ingredients 9% WW drug benzoyl peroxide. PartA Dimethicone Copolyol 1.OO Cyclomethicone 16.00 EXAMPLE 7 Cyclomethicone/Dimethiconol 3.00 Part B Purified Water 31.00 Gluconolactone 1O.OO Benzoyl Peroxide--Polyhydroxy Acid Cleanser— Propylene Glycol 8.OO Irritation Assessment Strong Ammonia Solution To desired pH Part C Purified Water 14.00 0047. In order to evaluate the irritation potential of 7.5% 75% Benzoyl Peroxide 13.33 Sodium Dioctylsodiumsulfosuccinate O.O6 benzoyl peroxide plus 10% polyhydroxy acid containing Enhancement Preservative QS cleansers, four formulation prototypes were tested versus a Additives Purified Water QS to 100% mild, commercially available cleanser that did not contain benzoyl peroxide in a modified cumulative irritation test. 0044) Typical Preparation Method: Prepare Part A by 0048 Six subjects entered into the study, Subjects were blending all the ingredients of Part A. Prepare Part B by not currently taking any medications including anti-inflam blending all the ingredients of Part Bas described in Example matory agents, antibiotics, and/or anti-histamines. Subjects 1 and adjust to the desired pH with an alkaline base. Enhance were not pregnant or nursing and were between the ages of ment additives are added as desired. Reduce particle size of 18-70. The subjects had no known allergies to alpha or poly Part C to appropriate distribution as described in Example 1. hydroxyacids, Sunscreens, or other skin care products. Sub Mix Part B and C together and then add the Part BC mixture jects were instructed not to apply any moisturizers, lotions or to Part A with mixing to form a water-in-silicone gel. any other products to the test area. Subjects were instructed not to use body Scrubs or exfoliants, washcloths, loofahs, or EXAMPLE 5 sponges on the test area. Subjects were instructed not to Swim, use a sauna, or receive Sun exposure attanning salons on their Polyhydroxy Acid and Polyhydroxy Bionic Acid— back for the duration of the study. Subjects were permitted to Thritation Potential shower, but were instructed to avoid exposing the test area to 0045. A 14-day cumulative irritation study was conducted direct streams of water or excessive soaking. on 24 healthy subjects to evaluate irritation potential of a 0049. Prior to the first patch application, the test sites were commercially available polyhydroxy acid product containing wiped with 70% isopropyl alcohol and allowed to dry. Using 4% lactobionic acid +8% gluconolactone cream (pH 3.8). a 1 cc syringe, approximately 0.2 ml of each test material was The product was tested in comparison to a mild irritant (0.1% applied to a patch (TruMedTechnologies Inc.) and to the back sodium lauryl sulfate solution) and a negative control (0.9% on either side of the spine. Semi-occlusive patches were used sodium chloride solution (saline)). Test products were for the products containing benzoyl peroxide for the first 4 applied underfull occlusion for days 1 to 14, and observations days of the study so as to avoid any severe irritation that may were made daily including weekends. The polyhydroxy acid occur over the weekend. An occlusive patch was used for the cream scored Statistically equivalently in irritation potential non-benzoyl peroxide containing product at the onset of the to normal saline, and significantly less than the Sodium lauryl study and all products were patched occlusively starting on US 2008/011.3037 A1 May 15, 2008

Monday. The cleansers were diluted to 10% prior to applica 0065 1=Mild erythema covering most of the test site tion to simulate in-use conditions. 0.066 2–Moderate erythema, possible presence of mild 0050. Initial patching took place on a Thursday. Daily edema applications and readings took place on Friday and the fol 0067. 3-Marked erythema, edema lowing week, Monday through Friday, with the last Friday as 0068 4-Severe erythema, edema, vesiculation, bullae, a reading day only. The patches applied on the first Friday and/or ulceration remained in place over the weekend and were removed on 0069. If at any time an evaluation score of 3 was given, Monday. There were a total of 6 readings over an 8-day product application was discontinued and a score of 3 was period. The subjects wore the patches for approximately 24 assigned for the duration of the study. The prototype 7.5% hours at a time and reported to the lab each weekday to have benzoyl peroxide+10% gluconolactone cleanser was signifi the patches removed and to have fresh patches applied. cantly less irritating (score 358) than the high strength (8%) 0051. The sites were marked to ensure the continuity of comparator benzoyl peroxide foaming cleanser (score 706). repetitive patch applications. The subjects were instructed to There was a trend toward less irritation (not significant) ver take care not to wash off the marks above each patch. sus the low strength (4%) benzoyl peroxide foaming cleanser 0052 Prior to re-application, the test sites were evaluated (score 703). The 5% benzoyl peroxide--10% gluconolactone using the following scoring scale: cleanser scored lower (score 474.5) than both the 4% (score 0053 0=No visible reaction 703) and 8% (score 706) benzoyl peroxide cleanser controls, 0054 +(0.5)=Barely perceptible or spotty erythema however the results were not significant. The controls: 0.9% 0055 1=Mild erythema covering most of the test site sodium chloride solution (saline) and no treatment were sig 0056 2=Moderate erythema, possible presence of mild nificantly less irritating than the benzoyl peroxide containing edema formulations as expected. 0057. 3-Marked erythema, edema 0058 4=Severe erythema, edema, vesiculation, bullae, and/or ulceration EXAMPLE 9 0059) Ifat any time during the study a test site exhibited a Benzoyl Peroxide--Polyhydroxy Acid Leave-On score of 3 or greater, the application of the test material to the Treatment Irritation Assessment site was discontinued. The site was assigned the 3 or greater score for the duration of the test. If a subject could not tolerate 0070. In order to evaluate the irritation potential of two a test material, the patch was removed at the time of complaint benzoyl peroxide plus 10% polyhydroxy acid containing and that score was assigned for the duration of the test. leave-on treatments. One contained 5% benzoyl peroxide and 0060 Total cumulative irritation scores for the four ben one contained 7.5% benzoyl peroxide in prototype lotions. Zoyl peroxide-polyhydroxy acid containing cleansers were The prototypes were tested versus two leading, commercially between 29.5 and 34.5 out of a maximum possible score of available treatments that contained 10% benzoyl peroxide in 108. Three of four prototype cleansers caused a single 3 score a modified cumulative irritation test. on the last day of grading; the fourth prototype caused a (0071 Six subjects entered into the study. Subjects were maximum score of 2.5. The non-irritating control cleanser not currently taking any medications including anti-inflam scored 18. The benzoyl peroxide plus polyhydroxy acid matory agents, antibiotics, and/or anti-histamines. Subjects cleansers were relatively well tolerated under the exaggerated were not pregnant or nursing and were between the ages of conditions of occlusion. 18-70. The subjects had no known allergies to alpha or poly hydroxyacids, sunscreens, or other skin care products. Sub EXAMPLE 8 jects were instructed not to apply any moisturizers, lotions or Benzoyl Peroxide--Polyhydroxy Acid Cleanser— any other products to the test area. Subjects were instructed not to use body scrubs or exfoliants, washcloths, loofahs, or Irritation Assessment sponges on the test area. Subjects were instructed not to Swim, 0061. A 14-day cumulative irritation study was conducted use a sauna, or receive sun exposure attanning salons on their on 27 healthy subjects to evaluate irritation potential of a back for the duration of the study. Subjects were permitted to prototype cleanser containing 5% benzoyl peroxide--10% shower, but were instructed to avoid exposing the test area to gluconolactone; a prototype cleanser containing 7.5% ben direct streams of water or excessive soaking. zoyl peroxide--10% gluconolactone; two control benzoyl 0072 Prior to the first patch application, the test sites were peroxide containing foaming cleansers without polyhydroxy wiped with 70% isopropyl alcohol and allowed to dry. Using acids, at a lower strength (4% benzoyl peroxide) and higher a 1 cc syringe, approximately 0.2 ml of each test material was strength (8% benzoyl peroxide); and the controls: 0.9% applied to a patch (TruMedTechnologies Inc.) and to the back sodium chloride solution (saline) and no treatment. Cleansers on either side of the spine. Initial patching took place on a were diluted with water to a concentration of 10% to simulate Thursday. Semi-occlusive patches were used for the first 4 wash off conditions. All test products were applied under days of the study so as to avoid any severe irritation that may occlusion on visits 1 to 4 and were converted to open patch occur over the weekend, and all products were patched occlu (i.e. no patch) on visits 5through 10 due to observed moderate sively starting on Monday. skin irritation with some of the tested formulations. Skin 0073. Initial patching took place on a Thursday. Daily irritation scores were collected at 10 observation time points applications and readings took place on Friday and the fol on weekdays only over the 14-day testing period. lowing week, Monday through Friday, with the last Friday as 0062 Prior to re-application, the test sites were evaluated a reading day only. The patches applied on the first Friday using the following scoring scale: remained in place over the weekend and were removed on 0063 0=No visible reaction Monday. There were a total of 6 readings over an 8-day 0064 +(0.5)=Barely perceptible or spotty erythema period, The subjects wore the patches for approximately 24 US 2008/O 113037 A1 May 15, 2008 hours at a time and reported to the lab each weekday to have applications. Greater than 80% of the subjects rated the pro the patches removed and to have fresh patches applied. totype to be mild, gentle, non-stinging and non-burning on 0074 The sites were marked to ensure the continuity of skin. The benzoyl peroxide treatment with polyhydroxy acid repetitive patch applications. The Subjects were instructed to was non-irritating when applied with a pad. take care not to wash off the marks above each patch. 0075 Prior to re-application, the test sites were evaluated EXAMPLE 12 using the following scoring scale: Benzoyl Peroxide--Polyhydroxy Acid Cleanser 0076 0=No visible reaction 0077 +(0.5)=Barely perceptible or spotty erythema Evaluation Vehicle Assessment 0078 1=Mild erythema covering most of the test site 0086. In order to evaluate the effect of vehicle modifica 0079 2=Moderate erythema, possible presence of mild tions on product preference, a panel of five Volunteers com edema pared two test wash-off cleanser formulations. The first for 0080. 3-Marked erythema, edema mulation contained 7.5% benzoyl peroxide plus 10% 0081 4-Severe erythema, edema, vesiculation, bullae, gluconolactone without dimethicone, and the second formu and/or ulceration lation contained 7.5% benzoyl peroxide plus 10% plus 3% 0082 Ifat any time during the study a test site exhibited a dimethicone. The overall opinion of the product containing score of 3 or greater, the application of the test material to the 3% dimethicone was statistically preferred (p<0.05) over the site was discontinued. The site was assigned the 3 or greater formulation without dimethicone. score for the duration of the test. If a subject could not tolerate 0087 While the invention has been described with refer a test material, the patch was removed at the time of complaint ence to particularly preferred examples and embodiments, and that score was assigned for the duration of the test. those skilled in the art will appreciate that various modifica 0083. The total cumulative irritation scores for the two tions may be made to the invention without departing from the benzoyl peroxide-polyhydroxy acid containing treatments spirit and scope thereof. were nearly equivalents, scoring 21.5 and 20 for the 7.5% and What is claimed is: 5% benzoyl peroxide plus 10% gluconolactone formulations 1. A composition comprising a) an oxidative pharmaceu respectively. The 10% benzoyl peroxide formulations scored tical drug and b) a polyhydroxy acid or polyhydroxylactone. 33 and 25.5. The 5% and 7.5% benzoyl peroxide plus poly 2. The composition of claim 1, wherein the polyhydroxy hydroxy acid treatments were tolerated well under the condi acid or polyhydroxy lactone is selected from the group con tion of this study. There is no advantage pertaining to irrita sisting of gluconic acid, gluconolactone, ribonic acid, ribono tion potential in choosing a lower strength (5%) benzoyl lactone, galactonic acid, galactonolactone, glucoheptonic peroxide plus polyhydroxy acid treatment. With the addition acid, glucoheptonolactone, glucuronic acid, glucuronolac of polyhydroxy acid, the irritation potential of the test formu tone, galacturonic acid, galacturonolactone, glucaric acid, lations remains lower than commercially available bench glucarolactone, galactaric acid and galactarolactone. marks. 3. The composition of claim 1, wherein the polyhydroxy acid or polyhydroxy lactone is an aldonic acid or aldonolac EXAMPLE 10 tone comprising the following structure: Benzoyl Peroxide--Polyhydroxy Acid Treatment— Irritation Assessment R(CHOH),CHOHCOOH where R is H or an alkyl group and n is an integer from 1-9. 0084. A 14-day cumulative irritation study was conducted 4. The composition of claim 1, wherein the polyhydroxy on 27 healthy subjects to evaluate the irritation potential acid and polyhydroxylactone is an aldaric acid or aldarolac associated with a commercially available 8% benzoyl perox tone comprising the following structure: ide gel, a commercially available 4% benzoyl peroxide gel, a prototype 7.5% benzoyl peroxide+10% gluconolactone HOOC(CHOH),CHOHCOOH lotion and controls: 0.9% sodium chloride solution (saline) or where n is an integer from 1-9. no treatment. All test products were applied under occlusion 5. The composition of claim 1, wherein the polyhydroxy on visits 1 to 4, on open skin without a patch on visit 5, and acid and polyhydroxy lactone is an alduronic acid or aldu under semi-occlusion on visits 6 to 10. Product application ronolactone comprising the following structure: was changed to manage the rapid development of irritation with some of the tested formulations. The 8% benzoyl per HOOC(CHOH),CHOHCHO oxide gel was directionally more irritating than the 4% ben where n is an integer from 1-9. Zoyl peroxide gel and 7.5% benzoyl peroxide--10% glucono 6. The composition of claim 1, wherein the oxidative phar lactone. Application of 0.9% sodium chloride solution maceutical drug is a peroxide, peracid, or Superoxide. (saline) and no treatment were significantly less irritating 7. The composition of claim 1, wherein the oxidative phar than the three benzoyl peroxide formulations. maceutical drug is selected from the group consisting of benzoyl peroxide, carbamide peroxide, coal tar, glutathione, EXAMPLE 11 hydrogen peroxide, iodine, juniper tar, lipoic acid, NAD", Benzoyl Peroxide--Polyhydroxy Acid Treatment on NADP", nitrogen oxide, oxygen, pine tar, potassium per Pads—Irritation Assessment manganate, povidone-iodine, perbenzoic acid, Sulfur, Sulfur dioxide, Sodium borate, Sodium perborate, shale tar, 0085. An evaluation of a prototype lotion containing 5% ubiquinone and wood tar. benzoyl peroxide--10% gluconolactone delivered using indi 8. The composition of claim 1, wherein the oxidative phar vidual pads was carried out on 58 volunteers. Subjects maceutical drug is benzoyl peroxide and the polyhydroxy applied the product to cleansed facial skin in two separate lactone is gluconolactone. US 2008/O 113037 A1 May 15, 2008

9. The composition of claim 1, wherein the concentration 15. The method of claim 12, wherein the polyhydroxy acid of the oxidative pharmaceutical drug ranges from about 0.1% or polyhydroxy lactone is an aldonic acid or aldonolactone to about 30% by weight, based on the total weight of the comprising the following structure: composition. 10. The composition of claim 1, wherein the concentration R(CHOH),CHOHCOOH of the polyhydroxy acid or polyhydroxylactone ranges from where R is H or alkyl group and n is an integer from 1-9. about 0.1% to about 50% by weight, based on the total weight 16. The method of claim 12, wherein said polyhydroxy of the composition. acid or polyhydroxy lactone is an aldaric acid or aldarolac 11. The composition of claim 1, further comprising an tone comprising the following structure: additional pharmaceutical or topical agent for synergetic or HOOC(CHOH),CHOHCOOH synergistic effect. 12. A method for treating or preventing cosmetic condi where n is an integer from 1-9. tions or dermatological disorders, comprising topically 17. The method of claim 12, wherein said polyhydroxy applying an effective amount of a composition comprising a) acid or polyhydroxylactone is an alduronic acid or aldurono an oxidative pharmaceutical drug and b) a polyhydroxy acid lactone comprising the following structure: or polyhydroxy lactone. HOOC(CHOH),CHOHCHO 13. The method of claim 12, wherein said cosmetic condi where n is an integer from 1-9. tions or dermatological disorders are selected from the group 18. A method of making a composition for topical admin consisting of disturbed keratinization, defective syntheses of istration comprisinga) an oxidative pharmaceutical drug and dermal components, and changes associated with aging of b) a polyhydroxy acid or polyhydroxy lactone, wherein the skin, nail and hair, and those indications which include dry method comprises: ness or loose of skin, nail and hair, Xerosis; ichthyosis; palmar preparing a solution comprising the polyhydroxy acid or and plantar hyperkeratoses; uneven and rough Surface of skin, polyhydroxy lactone, nail and hair; dandruff; Darier's disease; lichen simplex preparing a dispersion comprising the oxidative pharma chronicus; keratoses; acne; pseudofolliculitis barbae; ceutical drug, wherein the particle size of the oxidative eczema, psoriasis; itchy scalp and skin; pruritus; warts; her pharmaceutical drug is reduced to an appropriate distri pes; age spots; lentigines; melasmas; blemished skin; hyper bution so that the dispersion contains minimal grittiness keratoses; hyperpigmented skin; abnormal or diminished and minimal discernable feel when applied to the skin, Syntheses of collagen, glycosatinoglycans, proteoglycans and and elastinas well as diminished levels of such components in mixing the Solution comprising the polyhydroxy acid or the dermis; stretch marks; skin lines; fine lines; wrinkles: polyhydroxy lactone with the oxidative pharmaceutical thinning of skin, nail plate and hair, skin thickening due to drug dispersion. elastosis of photoaging, loss or reduction of skin, nail and hair 19. The method of claim 18, wherein the particle size of the resiliency, elasticity and recoilability; lack of skin, nail and oxidative pharmaceutical drug is reduced by wet milling, hair lubricants and luster, dull and older-looking skin, nail roller milling, crushing, or other typical methods of reducing and hair; and fragility and splitting of nail and hair. particle sizes. 14. The method of claim 12, wherein the polyhydroxy acid 20. The method of claim 18, wherein preparing a solution or polyhydroxylactone is selected from the group consisting comprising the antioxidant polyhydroxy acid or polyhydroxy of gluconic acid, gluconolactone, ribonic acid, ribonolactone, lactone further comprises heating the Solution and then cool galactonic acid, galactonolactone, glucoheptonic acid, gluco ing the solution prior to mixing the Solution with oxidative heptonolactone, glucuronic acid, glucuronolactone, galactu pharmaceutical drug dispersion. ronic acid, galacturonolactone, glucaric acid, glucarolactone, galactaric acid and galactarolactone. c c c c c