Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – 9,10-seco- cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
2000-08-31
2003-12-02
Pryor, Alton N. (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
9,10-seco- cyclopentanohydrophenanthrene ring system doai
C514S171000, C514S396000
Reexamination Certificate
active
06656928
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a composition for the treatment of rashes, dermatoses or lesions, which are known to be treated topically to improve or favorably alter the disease condition. Such rashes, dermatoses or lesions include acute, inflammatory reactions of the skin resulting from exposure to an adverse local environment (e.g., diaper rash, intertrigo, lichen simplex chronicus, balanitis, balanoposthitis), rashes, dermatoses or lesions caused by a fungal or yeast infection (e.g., tinea cruris, tinea pedis, tinea corporis, tinea versicolar, Candidal infections), rashes, dermatoses or lesions caused by an allergic or irritant reaction (such as that caused by poison ivy, poison oak or poison sumac, or other forms of contact dermatitis), rashes, dermatoses or lesions of a chronic nature (e.g. seborrheic dermatitis, psoriasis, atopic dermatitis) or caused by infection, irritation or aggravation of another condition such as occurs with acne, and other rashes, dermatoses or lesions.
Diaper rash is an irritant contact dermatitis, often secondarily infected with Candida organisms. It occurs as a result of constant exposure to an adverse local environment. Constant dampness is the main causative event, but numerous irritants add to the problem, including feces, urea, intestinal enzymes, detergent in the diaper, and even some medications. Moisture from the diaper further weakens the skin barrier, making the rash worse. The rash is often very red, may become raw, and can be quite painful for the child. Erythematous papules, vesicles or erosions, oozing, and ulceration may occur.
A variety of methods exist for treating diaper rash, including hydrocortisone cream (1% by weight), zinc oxide ointment, undecylenic acid, zinc undecylenate, nystatin cream, clotrimazole cream, or miconazole cream. Individually these therapies do not treat both the irritant dermatitis and the secondary Candida or dermatophyte infection.
Bowring et al (Bowring A W, Mackay D, Taylor F R: “The treatment of napkin dermatitis: a double-blind comparison of two steroid-antibiotic combinations,”
Pharmatherapeutica
(1984) vol. 3, #9; 613-617) compared a composition containing miconazole (2% by weight) and hydrocortisone (1% by weight) with a composition containing nystatin (100,000 i.&mgr;./gm), benzalkonium chloride (0.2% by weight), dimethicone (10% by weight), and hydrocortisone (0.5% by weight) in a study of 62 infants with moderate to severe diaper rash. Clinical assessments were made of erythema, weeping, tissue maceration, and infant irritability. Both treatments were reported to produce a high and similar overall cure rate (80% and 84% respectively), with a significant improvement within 48 hours in the majority of cases. While these results are encouraging, a more rapid and complete clinical response is desired.
Shankland et al.(Shankland G S, Richardson M D: “Comparative in-vivo activity of clotrimazole and a clotrimazole/hydrocortisone combination in the treatment of experimental dermatophytosis in guinea pigs,”
Journal of Antimicrobial Chemotherapy
(1990) 25, 825-830), describe the use of formulations containing hydrocortisone and clotrimazole for the treatment of dermatophyte infections Guinea pigs infected with
Trichophyton mentagrophytes var. mentagrophytes
were treated with once daily application of 1% by weight clotrimazole alone, 1% by weight hydrocortisone alone, base alone, a combination of 1% by weight clotrimazole and 1% by weight hydrocortisone, or no treatment at all. Clinically, the animals receiving combination therapy (clotrimazole plus hydrocortisone) were reported to have improved most quickly and cultures were negative after two treatments. Histological examination showed resolution of the infection and little inflammation.
An open, non-comparative study was performed to assess the effectiveness, acceptability and tolerability of a 1% by weight clotrimazole plus 1% by weight hydrocortisone cream in the treatment of 112 infants with napkin dermatitis (diaper rash) (Jaffe G V, Grimshaw J J: “An open trial of clotrimazole plus hydrocortisone cream in the treatment of napkin dermatitis in general practice,”
Pharmatherapeutica
, (1985), 4, 314-318). There was significant improvement in erythema, irritation and pustulation in all but a few patients, and 92% of the patients were considered to have been cured or markedly improved after 7 to 14 days of twice daily application. Again, while these results are encouraging, a more rapid and complete clinical response is desired.
A variety of methods have been used for the treatment of fungal infections including the use of potassium iodide, Castellani's paint, gentian violet, Whitfield's ointment, undecylenic acid, antibiotics (e.g. nystatin, fungizone and amphotericin B), griseofulvin, the imidazole antifungal agents such as miconazole, clotrimazole, econazole, ketoconazole, oxiconizole and sulconazole, the allylamine antifungal agents such as naftifine and terbinafine, the benzylamines such as butenafine HCl, the hydroxypyridone agents such as ciclopirox, the chlorinated iodopropynyl trichlorophenyl ether agents such as haloprogin, as well as tolnaftate, thymol, and tinver. Nystatin, fungizone, naftifine, and terbinafine, however, are only effective against yeast (Candida) and the imidazole compounds while effective in treating both dermatophytes and yeasts (Arndt, Kenneth A.,
Manual of Dermatologic Therapeutics
, 5
th
edition, 1995, Little, Brown and Co., page 290) often do not provide rapid relief.
The fungal infections are commonly associated with signs of erythema and scaling and with symptoms of itching or painful burning. Clinical treatment for fungal disease requires at least two to four weeks for complete relief of symptoms. More recently, it has been found that fungal infections can be effectively treated with a combination product containing corticosteroids and imidazole antifungal agents (see above referenced studies). It is known that the sensitivity of fungal organisms varies with their life cycles; spores are more resistant to treatment than are mycelia. Steroids may induce fungal spores to produce mycelia, thereby making them more sensitive to treatment. Also, steroids are known to produce vasoconstriction at the site of application. This activity may delay or prevent the elimination of the antifungal agent from the application site, permitting the antifungal agent to remain in the epidermis for longer periods of time. It is therefore believed that a locally applied anti-inflammatory agent would offer direct and immediate relief for the inflammatory component of the lesion. The combination product should then provide fast relief of symptoms and eradicate the infection. Based on this concept, certain combinations of an antifungal agent and an anti-inflammatory agent have recently been developed for treatment of fungal disease. Currently, the commercially available combination products using this concept are Lotrisone cream (clotrimazole 1% by weight/betamethasone dipropionate 0.05% by weight), Daktacort cream (miconazole nitrate 2% by weight/hydrocortisone 1% by weight) and Canesten HC cream (clotrimazole 1% by weight/hydrocortisone 1% by weight).
It has been reported Lotrisone cream was therapeutically and mycologically better than clotrimazole 1% by weight and betamethasone dipropionate 0.05% by weight alone. See e.g., Wortzel, M.Y., H., Cutis 30: 258 (1982) and Katz et al. Cutis, 34(2), 183-8 (1984). Notwithstanding its clinical advantages, Lotrisone cream possesses some undesirable attributes. It contains a rather strong fluorinated steroid, betamethasone dipropionate, which can be cutaneously dangerous to use in intertrigious regions for extended periods. Potential side effects include skin atrophy, rebound phenomenon, telangiectasia, and danger to infants and small children due to possible suppression of the hypothalamic-pituitary-adrenal axis if used it too large a quantity. The corticosteroid triamcinalone is also a fluorinated steroid. It is mixed with nystatin in Mycolo
Pryor Alton N.
Senniger Powers Leavitt & Roedel
LandOfFree
Composition for the topical treatment of rashes, dermatoses... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Composition for the topical treatment of rashes, dermatoses..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Composition for the topical treatment of rashes, dermatoses... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3095843