FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"TOPICAL FORMULATION CONTAINING ALCLOMETASONE DIPROPIONATE 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:
The present invention relates to a topical formulation for treatment of dermatoses, acne vulgaris caused by Propionibacterium acne and Staphylococcus species and sycosis vulgaris comprising corticosteroid along with broad-spectrum anti-bacterial agent of synthetic quinolone group.
Particularly, the instant invention relates to a combination of Alclometasone dipropionate and Nadifloxacin in topical formulation, specifically, in the form of cream, ointment, lotion, gel etc and the process for manufacturing thereof.
BACKGROUND OF INVENTION:
The present invention provides a combination of Alclometasone dipropionate and Nadifloxacin, which is used for the management of corticosteroid responsive dermatoses, acne vulgaris caused by Propionibacterium acne and Staphylococcus sp and sycosis vulgaris.
Acne vulgaris (commonly called acne) is a skin condition caused by changes in the pilosebaceous units (skin structures consisting of a hair follicle and its associated sebaceous gland). Severe acne is inflammatory, but acne can also manifest in non¬inflammatory forms. Acne lesions are commonly referred to as pimples, blemishes, spots, zits, or acne.
Sycosis vulgaris, more popularly known as Barber's itch, caused by pus germs which enter openings of the skin such as the hair sacs. This disease may be contracted in shaving, through use of towels, brushes, or combs in public establishments, and also through contact with pillows, lounges, and reclining chairs of public resting places. Neither heredity, nor the act of shaving favors this condition; however, a lowering of the body resistance would appear to be a contributing factor, as these particular germs seem to be present on the skin of most persons. The constant bathing of the upper lip .by
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discharges from colds is a rather common source of barber's itch confined to the upper
up.
Essentially, these skin diseases are characterized by itching and inflammation. The constant scratching of the inflamed region results in loss of barrier functions of the skin, which leads to invasion of the lower epidermal layers by pathogenic bacteria. Many patients resort to home remedies or OTC preparations which are inherently irritant, this complicates the clinical picture. The treating physician needs to control signs and symptoms of inflammation and at the same time control associated bacterial infection. 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 a speedy recovery.
Alclometasone dipropionate was first disclosed in US4124707. Alclometasone dipropionate is a synthetic glucocorticoid steroid for topical use in dermatological preparation as an anti-inflammatory, anti-puritic agent, anti-allergic, anti-proliferative and vasoconstrictive agent. Chemically Aloclometasone is known as [7-chloro-ll-hydroxy- 10,13,16-trimethyl-3-oxo-17- (2-propanoyloxyacetyl)- 7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl] propanoate, having a following structure;
CHzOCCHjCHs
l

Alclometasone dipropionate inhibits phospholipase A2 by inducing production of lipocortins; inhibits synthesis of arachidonic acid, prostaglandins and leukotrienes acid;
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reduce release of cytokines from lymphocytes and other mediators of inflammation, Thereby reducing inflammation.
Nadifloxacin was first discloses in US patent no. US4399134. Nadifloxacin is a fluoroquinolone antibiotic used for treatment of acne vulgaris. It is also used to treat bacterial skin infections. Chemically Nadifloxacin is known as 9-Fluoro-8-(4-hydroxy-piperidin-l-yl)-5-methyl-l-oxo-6, 7-dihydro-l/f, 5H-pyrido [3,2,l-ij]quinoline-2-carboxylic acid, C19H21FN2O4, having structural formula as follows:
o o

Nadifloxacin inhibits the enzyme DNA gyrase that is involved in bacterial DNA synthesis and replication, thus inhibiting the bacterial multiplication.
A patented combination of a DNA gyrase inhibitor or quinolones/fluoroquinolones and corticosteroid for treatment of skin disease has been disclosed in US4844902 assigned to Bayer Aktiengesellschaft, Germany. The said patent discloses a topical pharmaceutical formulation for treatment or prophylaxis of skin diseases. The said composition comprising a quinolone selected from ciprofloxacin, norfloxacin, perfloxacin, amifloxacin, pirfloxacin, ofloxacin and enoxacin, and the corticosteroid. The patent particularly describes use of this combination in therapy of oral cavity; however, it does not disclose specific combination comprising Alclometasone dipropionate and Nadifloxacin.
OBJECT OF THE INVENTION:
The main object of present invention is to provide a topical formulation comprising therapeutically effective amounts of Alclometasone dipropionate and Nadifloxacin for
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treatment of dermatoses, acne vulgaris caused by Propionibacterium acne as well as sycosis vulgaris.
SUMMARY OF THE INVENTION:
This invention discloses the topical formulation comprising a corticosteroid, Alclometasone dipropionate along with a broad-spectrum anti-bacterial agent, Nadifloxacin of synthetic quinolone group; in form of cream , ointment, lotion , gel etc having synergistic effect against acne vulgaris caused by Propinibacterium acne and Staphylococcus sp. susceptible bacteria as well as sycosis vulgaris.
DETAILED DESCRIPTION OF INVENTION:
The invention will now be described in details in connection with certain preferred and optional embodiments so that various aspects thereof may be more fully understood and appreciated
The present invention relates to a topical formulation comprising Alclometasone dipropionate, a corticosteroid along with Nadifloxacin, a broad-spectrum anti-bacterial agent of synthetic quinolone group; specifically in the form of cream and ointment for treatment of acne vulgaris and sycosis vulgaris. Further, the present invention relates to process for manufaturing thereof.
In preferred embodiment the topical cream comprises therapeutically effective amounts of Alclometasone dipropionate in combination with Nadifloxacin. The formulation of embodiment further comprises a penetration enhancer, a chelating agent, an emulsifying agent, a preservative, and an antioxidant.
The formulation of instant invention comprises a penetration enhancer. For the purpose of present invention penetration enhancer can be selected form fatty alcohols, fatty acid esters, fatty acids, fatty alcohol esters, solvents either alone or in combination. The preferred penetration enhancers are selected from the glycols, more preferably propylene glycol or Hexylene Glycol in range of 10-24%.
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The said cream formulation further comprises a chelating agent. The chelating agents used in present invention is ethylenediaminetetraacetic acid, more preferably the chelating agent is disodium salt of EDTA or Disodium edtate in range of 0.005-0.2%.
One or more emulsifying agents selected form group of Cetostearyl alcohol, Cetomacrogol 1000 and microcrystalline wax.
Preservatives are selected from the group of chlorocresol, methyl paraben and propyl paraben.
The antioxidant is selected from tocopherols, preferably a-Tocopherol in range of 0.01 -0.05% or Butylated Hydroxy Toluene in range of 0.1 - 0.5%
The buffering agent is citric acid in range of 0.01 - 0.1%
In further embodiment, a process for manufacturing of said topical cream formulation comprises following steps;
(a) Mixing oil phase and water phase under stirring for the emulsion formation at 60-70°C;
(b) Cooling emulsion as formed in step (a) till cream formation takes place; and
(c) Adding preservatives, penetration enhancer, antifoaming agent and active ingredient etc to cream formed in step (b) to form a stable cream formulation
(d) Active ingredient may be added before cream formation or while the cream formation is taking place


In another embodiment the formulation is in form of topical ointment. The ointment of current embodiment comprises therapeutically effective amounts of Alclometasone dipropionate and Nadifloxacin. The formulation further comprises one or more anti-oxidizing agents, surfactants, solubilizers, ointment base, and fatty base.
The anti-oxidizing agent as per the instant invention is any molecule capable of slowing or preventing the oxidation of other molecules or active pharmaceutical ingredient. The anti-oxidants used herein can be a natural antioxidants or synthetic antioxidants. The antioxidant is selected from vitamin E or other related tocopherols, Butylaied -hydroxytoluene (BHT), burylated hydroxyanisole (BHA). The preferred antioxidant is selected from a-Tocopherol and Butylated -hydroxytoluene (BHT).
The preferred surfactant for present invention is Sorbitan Sesquioleate in range of 0.1-2.0%.
The solubilizer selected from propylene glycol or Hexylene Glycol in the range of 5-15%.
An ointment base selected from the group of white soft paraffin, white bees wax and Cetyl alcohol.
A fatty base selected from lanolin anhydrous and liquid paraffin.
A further embodiment provides process for manufacturing of said topical ointment formulation comprises following steps;
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(a) Melting and mixing the oil base excipients;
(b) Adding the active ingredient under constant stirring, in oil base of step (a); and


(c) Adding penetration enhancer, surfactant, antioxidant to the mixture formed in step (b) for stable ointment preparation.
The instant invention is more specifically explained by following examples. However, it should be understood that the scope of the present invention is not limited by the examples in any manner. It will be appreciated by any person skilled in this art that the present invention includes following examples and further can be modified and altered within the technical scope of the present invention.
EXAMPLES:
Example 1:


Formulation for the Preparation of Cream:

Ingredients Concentration % w/w
Active Ingredients Alclomerasone
dipropionate
Dipropionate 0.05% w/w

Nadifloxacin 1.0% w/w
Emulsifier Cetostearyl alcohol 2-8%
Cetomacrogol 1000 0.5-4%
Macrocrystalline wax 2-5%
Oil base Light liquid paraffin 2-8%
White soft paraffin 2-8%
Preservative Methyl paraben 0.05-0.25%
Propyl paraben 0.01-0.1%
Chlorocresol 0.05-0.15%
Antioxidant a - Tocopherol 0.01-0.05%
Butylated Hydroxy Toluene 0.1 -0.5%

Penetration enhancer Propylene glycol 10-24%
Hexylene Glycol 10-24%
Chelating agent Disodium EDTA 0.005-0.2%
Buffering agent Citric acid 0.01-0.1%
Purified water Vehicle q. s.
Formulation for the Preparation of Ointment:

Ingredients Concentration
Active Ingredients Alclometasone
dipropionate
Dipropionate 0.05% w/w

Nadifloxacin 1.0% w/w
Antioxidant ct-Tocopherol 0.01-0.15%
Butylated-hydroxy toluene 0.1-0.5%
Surfactants Sorbitan Sesquioleate 0.1-2.0%
Solubilizer Propylene glycol 5-15%
Hexylene Glycol 5-15%
Ointment base White soft paraffin 80-95%
White bees wax 2-10%
Cetyl alcohol 2-10%
Fatty base Lanolin anhydrous 15-65%
Liquid paraffin 2-8%
Dated this the 03rd day of June, 2009
Dr. P. Aruna Sree Agent for the Applicant