FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"TOPICAL FORMULATION CONTAINING HALOBETASOL PROPIONATE
AND NADIFLOXACIN"


2. APPLICANT:
(a) NAME: Lyka Labs Limited.
(b) NATIONALITY: Indian Company incorporated under the
Indian Companies Act, 1956
(c) ADDRESS: 101, Shivshakti Industrial Estate, Andheri-Kurla Road,
Andheri (East), Mumbai - 400059, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention:


Technical field of invention:
This invention relates to the topical composition containing corticosteroid Halobetasol Propionate along with broad-spectrum anti-bacterial agent Nadifloxacin of synthetic quinolone group in the form of cream, ointment, gel, lotion, etc.
Background of the invention:
Halobetasol propionate, a synthetic corticosteroid is used for topical dermatological use. The corticosteroids constitute a class of primarily synthetic steroids used topically as an anti-inflammatory and anti-pruritic agent. Chemically halobetasol propionate is 21-chloro-6a, 9-difluoro-ll β -methylpregna-1, 4-diene-3-20-dione, 17-propionate, C25H31CIF2O5, having structural formula as follows:

Halobetasol propionate is used in 0.05% to treat swelling, inflammation, and itching associated with skin conditions such as eczema, dermatitis, rashes, insect bites, poison ivy, and allergies. It reduces the action of chemicals in the body that cause inflammation, redness, and swelling and itching caused by a number of skin conditions such as allergic reactions, eczema, and psoriasis.
Chemically Nadifloxacin is 9-Fluoro-8-(4-hydroxy-piperidin-l-yl)-5-methyl-l-oxo-6, 7-dihydro-lH, 5H-pyrido [3,2,l-ij]quinoline-2-carboxylic acid, C19H21FN2O4, having structural formula as follows:
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Nadifloxacin is used in concentration of 1.0% (OPC-7251) as antimicrobial agent belonging to the quinolone group and developed exclusively for topical administration. Nadifloxacin acts by inhibiting the formation of supercoiled DNA by DNA gyrase that is involved in bacterial DNA synthesis and replication, thus inhibiting bacterial multiplication. In preliminary studies, nadifloxacin has demonstrated activity against a broad range of Gram-positive (e.g., Staphylococcus aureus, methicillin-resistant S. aureus and Staphylococcus epidermidis) and Gram-negative (e.g., Pseudomonas aeruginosa) bacteria, including anaerobic (Propionibacterium acnes), as well as activity in vivo.
The present invention provides a topical formulation comprising Halobetasol Propionate (a corticosteroid) alongwith Nadifloxacin (an antimicrobial agent) as active ingredients, especially effective against inflammation and infection ensuring speedy recovery.
An article on "Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid" by Wolf- Ingo Worretl, Joachim W. Fluhr, accepted on 15.12.2005, discloses that a double-blind, vehicle-controlled study shows nadifloxacin cream to be superior to vehicle alone. The minimal inhibitory concentration of topically applied nadifloxacin towards P. acnes appears lower than that of tetracycline or minocycline. This point's to the fact that this topical antibiotic is potently bactericidal. Compared to seven other tested antibiotics (ciprofloxacin, penicillin, erythromycin, tetracycline, clindamycin, fusidic acid and gentamicin) nadifloxacin is effective against propionibacteria as well as staphylococci and exhibits the lowest rate of resistant pathogens. It further discloses typical adverse effects of topical 1 % nadifloxacin cream are local erythema and pruritus, while rare adverse effects are slight and negligible signs of skin irritation, itching, dryness and desquamation.
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"Halobetasol Propionate cream/ointment" by [E. FOUGERA & CO.] describes adverse reactions, which states that the most frequent adverse events reported for halobetasol propionate cream included stinging, burning or itching in 4.4% of the patients. Less frequently reported adverse reactions are dry skin, erythema, skin atrophy, leukoderma, vesicles and rash. The following additional local adverse reactions are reported infrequently with topical corticosteroids, and they may occur more frequently with high potency corticosteroids, such as halobetasol propionate cream. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striate and malaria.
Halobetasol propionate cream/ointment is marketed under the brand name Ultravate and it has been observed that some of the medication used in Ultravate, is inevitably absorbed through the skin and into the bloodstream. If applied over a large area, or under an airtight dressing, the drug can cause a number of unwanted side effects, including increased sugar in the blood and urine, and a set of symptoms called Cushing's syndrome, characterized by a moon-shaped face, emotional disturbances, high blood pressure, weight gain, and growth of body hair in women.
Object of the invention:
The main object of the invention is to provide the topical composition comprising Halobetasol Propionate and Nadifloxacin useful for the management of corticosteroid responsive dermatoses acne vulgaris formulations and sycosis vulgaris.
Summary:
This invention discloses the topical composition containing corticosteroid Halobetasol Propionate along with broad-spectrum anti-bacterial agent Nadifloxacin of synthetic quinolone group in the form of cream, ointment, gel, lotion etc having synergistic effect against acne vulgaris caused by propini bacterium acnes and staphylococcus sp. susceptible bacteria.
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Detailed description of the invention:
The present invention describes topical composition for treatment of acne vulgaris, which comprises of Halobetasol a synthetic corticosteroid with Nadifloxacin an antimicrobial agent in the form of cream, ointment, gel, lotion, etc.
In accordance to the above objectives, the present invention provides the topical composition which comprises therapeutically effective amount of Halobetasol with Nadifloxacin along with pharmaceutically accepted ingredients.
Majority of skin diseases present with itching and inflammation resulting into loss of barrier functions of the skin. This leads to invasion of the epidermis layers of skin by pathogenic bacteria. The combination of the present invention is used for the management of corticosteroid responsive dermatoses acne vulgaris formulations and sycosis vulgaris. The above combination works synergistically against acne vulgaris caused by propini bacterium acnes and staphylococcus sp. susceptible bacteria.
Many patients resort to home remedies or OTC preparations which are irritant in nature. This complicates the clinical picture. The treating physician needs to control signs and symptoms of inflammation and at the same time have to control associated bacterial infections. Failure to treat the bacterial infection while the patient is recommended a topical corticosteroid preparation leads to 'flare' of bacterial infection. A combination of corticosteroid with anti-infective agent takes care of inflammation and infection ensuring speedy recovery.
According to a preferred embodiment, the present invention further describes topical composition of Halobetasol with Nadifloxacin as combination of high potency corticosteroid with broad-spectrum topical anti-bacterial drug in the form of cream, ointment, gel, lotion, etc.
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The cream can be prepared by mixing oil phase and water phase under stirring for the emulsion formation at 60-70°c, this is followed by cooling till cream formation takes place followed by adding preservatives, penetration enhancer, antifoaming agent etc for the stable cream formation. Active ingredient may be added before cream formation or while the cream formation is taking place.
While the ointment is prepared by melting and mixing the oil base excipients, active ingredient is either dissolved or suspended in oil base and added under constant stirring, followed by adding penetration enhancer, surfactant, antioxidant, etc.
Lotion may be prepared by mixing oil phase and water phase under stirring for the emulsion formation at 60-70°C, followed by adding preservatives, penetration enhancer, antifoaming agent etc for the stable lotion formation. Active ingredient may be added before emulsion formation or while the emulsion formation is taking place.
Gel may be prepared by soaking carbopol in purified water overnight. Active drugs maybe dissolved in co-solvent and added to carbopol gel and mixed properly, then by adjusting pH with triethanolamine or Diethanolamine or sodium hydroxide solution. Other inactives may be added to product.
Dated this 21st day of July, 2008

Dr. Gopakumar G. Nair Agent for the Applicant