Method for the treatment or prevention of dermatological disorders with a cyclooxygenase-2 inhibitor alone and in combination with a dermatological treatment agent and compositions therewith

• US 20050014729A1
• Filed: 06/03/2004
• Published: 01/20/2005
• Est. Priority Date: 07/16/2003
• Status: Abandoned Application

• Current Assignee: Pharmacia Corporation (Pfizer Inc.)
• Original Assignee: Pharmacia Corporation (Pfizer Inc.)
• Inventors: Pulaski, Steven P.
• Application Number:
  US10/860,307
• Publication Number:
  US 20050014729A1
• Time in Patent Office: Days
• US Class Current: 514/165
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

A method for preventing or treating dermatological disorders and dermatological disorder-related complications in a subject involves a monotherapy with a Cox-2 inhibitor or a combination therapy with a Cox-2 inhibitor and a dermatological treatment agent. Also described are therapeutic compositions comprising a Cox-2 inhibitor and a dermatological treatment agent. Pharmaceutical compositions and kits for implementing the present method are also described.

Claims

1. A method of preventing or treating dermatological disorders and dermatological disorder-related complications in a subject comprising administering to the subject a Cox-2 inhibitor.

2. The method according to claim 1, wherein the Cox-2 inhibitor is administered to the subject in combination with one or more dermatological treatment agents.

3. The method according to claim 1 or 2, wherein the subject is one that is in need of the prevention or treatment of a dermatological disorder or a dermatological disorder-related complication.

4. The method according to claim 1, wherein the Cox-2 inhibitor comprises a non-steroidal anti-inflammatory drug.

5. The method according to claim 1, wherein the Cox-2 inhibitor is selected from the group consisting of ibuprofen, naproxen, benoxaprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, indoprofen, pirprofen, carprofen, oxaprozin, prapoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, diclofenac, fenclofenec, alclofenac, ibufenac, isoxepac, furofenac, tiopinac, zidometacin, acetyl salicylic acid, indometacin, piroxicam, tenoxicam, nabumetone, ketorolac, azapropazone, mefenamic acid, tolfenamic acid, diflunisal, podophyllotoxin derivatives, acemetacin, droxicam, floctafenine, oxyphenbutazone, phenylbutazone, proglumetacin, acemetacin, fentiazac, clidanac, oxipinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid, flufenisal, sudoxicam, etodolac, piprofen, salicylic acid, choline magnesium trisalicylate, salicylate, benorylate, fentiazac, clopinac, feprazone, isoxicam and 2-fluoro-a-methyl[1,1′

-biphenyl]-4-acetic acid, 4-(nitrooxy)butyl ester, and mixtures thereof.

6. The method according to claim 1, wherein the Cox-2 inhibitor comprises a Cox-2 selective inhibitor.

7. The method according to claim 6, wherein the Cox-2 selective inhibitor is selected from the group consisting of celecoxib, parecoxib, deracoxib, valdecoxib, etoricoxib, meloxicam, rofecoxib, lumiracoxib, RS 57067, T-614, BMS-347070, JTE-522, S-2474, SVT-2016, CT-3, ABT-963, SC-58125, nimesulide, flosulide, NS-398, L-745337, RWJ-63556, L-784512, darbufelone, CS-502, LAS-34475, LAS-34555, S-33516, SD-8381, prodrugs of any of them, and mixtures thereof.

8. The method according to claim 6, wherein the Cox-2 selective inhibitor comprises a tricyclic Cox-2 selective inhibitor.

9. The method according to claim 8, wherein the tricyclic Cox-2 selective inhibitor comprises at least one compound that is selected from the group consisting of celecoxib, parecoxib, deracoxib, valdecoxib, etoricoxib, rofecoxib, prodrugs of any of them, and mixtures thereof.

10. The method according to claim 8, wherein the Cox-2 selective inhibitor comprises at least one compound that is selected from the group consisting of celecoxib, parecoxib, valdecoxib, prodrugs of any of them, and mixtures thereof.

11. The method according to claim 8, wherein the Cox-2 selective inhibitor comprises celecoxib.

12. The method according to claim 6, wherein the Cox-2 selective inhibitor is a chromene Cox-2 selective inhibitor.

13. The method according to claim 12, wherein the chromene Cox-2 selective inhibitor is selected from the group consisting of

(S)-6-chloro-7-(1,1-dimethylethyl)-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid,

(2S)-6,8-dimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(2S)-6-chloro-8-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(2S)-8-ethyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid, and

(2S)-6-chloro-5,7-dimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, and mixtures thereof.

14. The method according to claim 2, wherein the dermatological treatment agent is selected from the group consisting of antibiotics, retinoids, antifungals, antiparasitics, corticosteroids, astrigents, antiseptics, antivirals, keratolytic agents, comedolytic agents, immunosuppressive agents, antihistamines, anaesthetics, and mixtures thereof.

15. The method according to claim 14, wherein the antibiotic is selected from the group consisting of penicillin, penicillin G, penicillin V, procaine, benzathine, cloxacillin, dicloxacillin, methicillin, nafcillin, oxacillin, azlocillin, carbenicillin, piperacillin, piperacillin plus tazobactam, ticarcillin, mezlocillin, cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, cephradine, cefaclor, cefamandole, cefmetazole, cefonicid cefotetan, cefoxitin, cefprozil, cefuroxime, loracarbef, cefepime, cefixime, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten ceftizoxime, ceftriaxone, Imipenem, meropenem, aztreonam, clavulanic acid, sulbactam, tazobactam, ampicillin, ampicillin plus sulbactam, amoxycillin, amoxicillin, amoxicillin plus clavulanate potassium, bacampicillin, clavulanic acid plus amoxycillin, aztreonam, imipenem, streptomycin, kanamycin, neomycin, gentamycin, tobramycin, amikacin, netilmicin, gentamicin, vancomycin, clindamycin, azithromycin, clarithromycin, clindamycin, roxithromycin, dirithromycin, spiramycin, josamycin, erythromycin, lincomycin, bacitracin, colistin, polymyxin B, bacitracin, amphotericin, nystatin, rifampicin, tetracycline, chlortetracycline, oxytetracycline, demeclocycline, minocycline, doxycycline, chloramphenicol, ciprofloxacin, enoxacin, grepafloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, cinoxacin, nalidixic acid, clindamycin, linezolid, spectinomycin, quinupristin, dalfopristin, trimethoprim, trimethoprim-sulfamethoxazole, sulfanilamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfamethizole, silver sulfadiazine, mafenide, and mixtures thereof.

16. The method according to claim 14, wherein the retinoid is selected from the group consisting of tretinoin, adapalene, isotretinoin, tazarotene, tretinoin trans retinoic acid, 2,4,6,8-nonatetraenoic acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl, ethyl ester, (all-E)-, Ro-40-0655, Ro-25-6760, Ro-25-9022, Ro-25-9716, benzoic acid, 4-[[3,5-bis(trimethylsilyl)benzoyl]amino]-, retinamide, N-(4-hydroxyphenyl)-, (2E,4E,6E)-7-(3,5-Di-tert-butylphenyl)-3-methylocta-2,4,6-trienoic acid, MDI-101, MDI-403, benzoic acid, 4-(1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl)-, benzoic acid, 4-(1-(5,6,7,8-tetrahydro-3,5,8,8-pentamethyl-2-naphthalenyl)ethenyl), (2E,4E)-3-methyl-5-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)- thiopen-2-yl]-penta-2,4-dienoic acid, SR-11262 F, BMS-181162, N-(4-hydroxyphenyl) retinamide, AGN-193174, LGD 1550, ALRT 1550, LG 100550, AGN 193101, LG 1550, ALRT 550, MX6, trans-retinoic acid, alitretinoin, 9-cis-retinoic, and mixtures thereof.

17. The method according to claim 14, wherein the antifungal is selected from the group consisting of clotrimazole, griseofulvin, undecylenic, econazole, miconazole, ketaconazole, sulconazole, oxiconazole, fluconazole, itraconazole, nystatin, naftifine, terbinafine, ciclopirox, butenafine, haloprogin, tolnaftate, and mixtures thereof.

18. The method according to claim 14, wherein the corticosteroid is selected from the group consisting of hydrocortisone, prednisone, fluprednisolone, dexamethasone, betamethasone, betamethasone valerate, methylprednisolone, fluocinolone acetonide, flurandrenolone acetonide, fluorometholone, cortisone, prednisolone, alclometasone, amcinonide, betamethasone, clobetasol, clocortolone, desonide, desoximetasone, diflorasone, fluocinonide, flurandrenolide, fluticasone, halcinonide, halobetasol, mometasone, flumethasone, prednicarbate, triamcinolone, and mixtures thereof.

19. The method according to claim 14, wherein the astrigent is selected from the group consisting of isopropyl alcohol, ethanol, methanol, propylene glycol, and mixtures thereof.

20. The method according to claim 14, wherein the antiseptic is selected from the group consisting of acetic acid, boric acid, gentian violet, hydrogen peroxide, carbamide peroxide, chlorhexidine, saline, mercurochrome, povidone iodine, polyhyroxine iodine, cresylate, aluminum acetate, and mixtures thereof.

21. The method according to claim 14, wherein the antihistamine is selected from the group consisting of azatadine, meclizine, promethazine bromodiphenhydramine, brompheniramine, brompheniramine maleate, carbinoxamine, chlorpheniramine, dexchlorpheniramine, diphenhydramine, doxylamine, phenindamine, pheniramine, phenyltoloxamine, pyrilamine, triprolidine, clemastine, dimenhydranate, cetirzine, terfenadine, astemizole, loratadine, acrivastine, hydroxyzine, meclozine, compazine, imipramine, doxopin, amitryptoline, tripelennamine, fexofenadine, azatadine, and mixtures thereof.

22. The method according to claim 14, wherein the anaesthetic is selected from the group consisting of benzocaine, butamben picrate, tetracaine, dibucaine, carbocaine, cocaine, chloroprocaine, mepivacaine, etidocaine, prilocaine, etidocaine, bupivicaine, lidocaine, fenamates, pyrrolealkanoic acids, pyrazolone derivatives, oxicams, pramoxine, and mixtures thereof.

23. The method according to claim 14, wherein the antiviral is selected from the group consisting of acyclovir, gancyclovir;

interferons, mono and polyclonal antibodies, thimerasol, idoxuridine, vidarabine, trifluridine, famciclovir, valacyclovir, penciclovir, ganciclovir, dipyridamole, impulsin, pleconaril, foscarnet, ribavirin, amantadine, rimantadine, cidofovir, ICI 130,685, zanamivir, oseltamivir, valganciclovir, aciclovir, idoxuridine, vidarabine, valacyclovir, and mixtures thereof.

24. The method according to claim 2, wherein the dermatological agent is selected from the group consisting of tretinoin, adapalene, azelaic acid, benzoyl peroxide, isotretinoin, triamcinolone acetonide, clindamycin, trimethoprim, spironolactone, sulfur in combination with an alcohol, sulfur in combination with sodium sulfacetamide, salicylic acid, tazarotene, minocycline, erythromycin, doxycycline, tetracycline, norgestimate/ethinyl estradiol, progesterone, estrogen/progesterone, ethinyl estradiol in combination with levonorgestrel, flutamide, sulfonamide, erythromycin in combination with benzoyl peroxide, resorcinol in combination with sulfur, diphenhydramine, prednisone, hydrocortisone, acetic acid, propylene glycol, clindamycin in combination with benzoyl peroxide, isopropyl alcohol, ethanol, methanol, chlorpheniramine, loratadine, cotrimoxazole, witch hazel, hydrogen peroxide, zinc oxide, fluocinonide, sulfur in combination with salicylic acid, glycolic acid, triclosan, tretinoin in combination with erythromycin, fexofenadine, zinc gluconate, cyclosporine, azathioprine, and mixtures thereof.

25. The method according to claims 1, 2 or 3, wherein the subject suffers from or is predisposed to one or more dermatological disorders selected from the group consisting of dermatological pain, dermatological inflammation, acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections, skin neoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneous infections, scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infections, rashes, erythrasma, impetigo, ecthyma, yeast skin infections, warts, molluscum contagiosum, trauma or injury to the skin, post-operative or post-surgical skin conditions, scabies, pediculosis, creeping eruption, eczemas, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme, erythema nodosum, grannuloma annulare, epidermal necrolysis, sunburn, photosensitivity, pemphigus, bullous pemphigoid, dermatitis herpetiformis, keratosis pilaris, callouses, corns, ichthyosis, skin ulcers, ischemic necrosis, miliaria, hyperhidrosis, moles, Kaposi'"'"'s sarcoma, melanoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, poison ivy, poison oak, contact dermatitis, atopic dermatitis, rosacea, purpura, moniliasis, candidiasis, baldness, alopecia, Behcet'"'"'s syndrome, cholesteatoma, Dercum disease, ectodermal dysplasia, gustatory sweating, nail patella syndrome, lupus, hives, hair loss, Hailey-Hailey disease, chemical or thermal skin burns, scleroderma, aging skin, wrinkles, sun spots, necrotizing fasciitis, necrotizing myositis, gangrene, scarring, and vitiligo.

26. The method according to claims 1, 2 or 3, wherein the subject suffers from or is predisposed to acne.

27. The method according to claims 1 or 2, wherein the administering is by a route selected from the group consisting of oral, topical, bucal, inhalation, intravenous, intramuscular, parenteral, subcutaneous, and infusion techniques.

28. The method according to claim 1 or 2, wherein the administering comprises a topical route.

29. The method according to claim 2, further comprising administering an amount of a Cox-2 inhibitor and an amount of a dermatological treatment agent wherein the amount of the Cox-2 inhibitor and the amount of the dermatological treatment agent together comprise a therapeutically effective amount.

30. A therapeutic composition comprising at least one Cox-2 inhibitor and one or more dermatological treatment agents.

31. The therapeutic composition according to claim 30, wherein the Cox-2 inhibitor comprises a Cox-2 selective inhibitor.

32. The therapeutic composition according to claim 30, wherein the Cox-2 selective inhibitor is selected from the group consisting of celecoxib, parecoxib, deracoxib, valdecoxib, etoricoxib, meloxicam, rofecoxib, lumiracoxib, RS 57067, T-614, BMS-347070, JTE-522, S-2474, SVT-2016, CT-3, ABT-963, SC-58125, nimesulide, flosulide, NS-398, L-745337, RWJ-63556, L-784512, darbufelone, CS-502, LAS-34475, LAS-34555, S-33516, SD-8381, prodrugs of any of them, and mixtures thereof.

33. The therapeutic composition according to claim 30, wherein the Cox-2 selective inhibitor comprises celecoxib.

34. The therapeutic composition according to claim 30, wherein the Cox-2 selective inhibitor is a chromene Cox-2 selective inhibitor.

35. The therapeutic composition according to claim 30, wherein the chromene Cox-2 selective inhibitor is selected from the group consisting of

(S)-6-chloro-7-(1,1-dimethylethyl)-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid,

(2S)-6,8-dimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(2S)-6-chloro-8-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(2S)-8-ethyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid, and

(2S)-6-chloro-5,7-dimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, and mixtures thereof.

36. A pharmaceutical composition comprising a Cox-2 inhibitor, a dermatological treatment agent, and a pharmaceutically acceptable carrier.

37. The pharmaceutical composition according to claim 36, wherein the Cox-2 inhibitor comprises a Cox-2 selective inhibitor.

38. The pharmaceutical composition according to claim 36, wherein the Cox-2 selective inhibitor is selected from the group consisting of celecoxib, parecoxib, deracoxib, valdecoxib, etoricoxib, meloxicam, rofecoxib, lumiracoxib, RS 57067, T-614, BMS-347070, JTE-522, S-2474, SVT-2016, CT-3, ABT-963, SC-58125, nimesulide, flosulide, NS-398, L-745337, RWJ-63556, L-784512, darbufelone, CS-502, LAS-34475, LAS-34555, S-33516, SD-8381, prodrugs of any of them, and mixtures thereof.

39. The pharmaceutical composition according to claim 36, wherein the Cox-2 selective inhibitor comprises celecoxib.

40. The pharmaceutical composition according to claim 36, wherein the Cox-2 selective inhibitor is a chromene Cox-2 selective inhibitor.

41. The pharmaceutical composition according to claim 36, wherein the chromene Cox-2 selective inhibitor is selected from the group consisting of

(S)-6-chloro-7-(1,1-dimethylethyl)-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid,

(2S)-6,8-dimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(2S)-6-chloro-8-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(2S)-8-ethyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid,

(S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid, and

(2S)-6-chloro-5,7-dimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid, and mixtures thereof.

42. A kit comprising one dosage form comprising a Cox-2 inhibitor and a second dosage form comprising a dermatological treatment agent.