FORM 2
THE PATENTS ACT 1970 (Act 39 of 1970)
PROVISIONAL SPECIFICATION (SECTION 10)
"PHARMACEUTICAL COMPOSITION CONTAINING LATANOPROST"
Glenmark Pharmaceuticals Limited, an Indian Company,
registered under the Indian company's Act 1957 and
having its registered office at
Glenmark Pharmaceuticals Limited, Glenmark House,
HDO - Corporate Bldg, Wing -A,
B.D. Sawant Marg, Chakala,
Andheri (East),
Mumbai - 400 099, India
THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION: AND THE MANNER IN,
WHICH IT IS TO BE PERFORME
1

PHARMACEUTICAL COMPOSITION CONTAINING LATANOPROST
BACKGROUND OF THE INVENTION
Technical Field
The present invention relates to a pharmaceutical composition containing Latanoprost in therapeutically effective in the treatment of Vitiligo and the process for preparing the same.
Description of the Related Art
Latanopost, a prostaglandin is a hormone-like substance (autacoid) that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid.
Latanoprost is a prostaglandin F2a analogue. Its chemical name is isopropyl-(Z)-7[(lR, 2R, 3R, 5(S)3, 5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate. Its molecular formula is C26H40O5 and its chemical structure is:

Latanoprost is a colorless to slightly yellow oil which is very soluble in acetonitrile and freely soluble in acetone, ethanol, ethyl acetate, isopropanol, methanol, and octanol. It is practically insoluble in water.
Prostaglandins exert considerable biologic activity. In order to enhance delivery and to improve chemical stability of prostaglandins, the carboxylic acid moiety on the omega chain
2

can be esterified, for instance with alkyl groups containing 1-10 carbons, especially 1-6 carbons e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, neopentyl or benzyl. Such esterified prodrugs of prostaglandins have been described in several patents and patent applications (see for instance EP 093380, EP 0364417 and W092/02496). Depending on the specific prostaglandin analogue other derivatives such as salts, e.g. the sodium salt, may also be used.
Latanoprost (la-TA-noe-prost) is used to treat certain kinds of glaucoma, a condition in relation to increased tension of the eye. Latanoprost appears to work by increasing the outflow of fluid (aqueous humour) from the anterior chamber of the eye. This lowers the intra-ocular pressure in the eye.
The present invention relates to the new use of latanoprost pharmaceutical composition for the treatment of Vitiligo.
Vitiligo (vit-ill-EYE-go) is a pigmentation disorder in which melanocytes (the cells that make melanin pigment) in the skin, the mucous membranes (tissues that line the inside of the mouth and nose and genital and rectal areas), and the retina (inner layer of the eyeball) are destroyed. As a result, white patches of skin appear on different parts of the body. The hair that grows in areas affected by vitiligo usually turns white.
The cause of vitiligo is not known, but researchers have several different theories. One theory is that people develop auto-antibodies that destroy the melanocytes of their own bodies. Another theory is that there is accumulation of indoles and free radicals in the melanocytes that are destructive to melanocytes. Finally, some people have reported that a single event such as sunburn or emotional distress triggered vitiligo; however, these events have not been scientifically proven to cause vitiligo. About 1 to 2 percent of the world's population have vitiligo.
Vitiligo seems to be more common in people with certain autoimmune diseases (diseases in which a person's immune system reacts against the body's own organs or tissues). These autoimmune diseases include hyperthyroidism (an overactive thyroid gland), adrenocortical insufficiency (the adrenal gland does not produce enough of the hormone called
3

corticosteroid), alopecia areata (patches of baldness), and pernicious anemia (a low level of red blood cells caused by failure of the body to absorb vitamin B-12). Scientists do not know the reason for the association between vitiligo and these autoimmune diseases.
Vitiligo may also be hereditary, that is, it can run in families. Children whose parents have the disorder are more likely to develop vitiligo.
People who develop vitiligo usually first notice white patches (depigmentation) on their skin. These patches are more common in sun-exposed areas, including the hands, feet, arms, face, and lips. Other common areas for white patches to appear are the armpits and groin and around the mouth, eyes, nostrils, navel, and genitals.
Vitiligo generally appears in one of three patterns. In one pattern (focal pattern), the depigmentation is limited to one or only a few areas. Some people develop depigmented patches on only one side of their bodies (segmental pattern). But for most people who have vitiligo, depigmentation occurs on many different parts of the body (generalized pattern). In addition to white patches on the skin, people with vitiligo may have premature graying of the scalp hair, eyelashes, eyebrows, and beard. People with dark skin may notice a loss of color inside their mouths.
W09511003 application assigned to STJERNSCHANTZ JOHAN SE; PHARMACIA AB SE; RESUL BAHRAM SEA claims the method for producing a composition containing prostaglandins, derivatives or analogues thereof for increasing pigmentation of tissues or modified tissues, e.g. hair, is disclosed. Among these, derivatives and analogues of prostaglandin F2a and prostaglandin E2 in particular, have been found suitable for the purpose .This application discloses prostaglandins very broadly and discloses its use in the treatment of vitiligo generically, but does not specify latanoprost for the treatment of Vitiligo.
Also, EP 1178833 patent assigned to NEXMED HOLDINGS INC US claims composition of a semi-solid consistency is provided for use in the manufacture of a topical medicament for the transdermal application of prostaglandin E 1. Latanoprost used as active by the inventors
4

of this present patent application used prostaglandin F2a agonist for dermal application and not for the transdermal application of prostaglandin E 1.
Surprisingly inventors of the present invention discovered after clinical trials that Latanoprost specifically from the category of prostaglandin is effective in the treatment of Vitiligo and can be manufactured in a cost efficient manner on a commercial scale in various dosage forms for topical application.
SUMMARY OF THE INVENTION
The first object of the invention is to provide a treatment for Vitiligo using therapeutically effective amount of prostaglandin such as latanoprost in a suitable therapeutic composition form.
The second object of this invention is treating vitiligo using Latanoprost composition to restore the function of the skin and to improve the patient's appearance.
Further aspect of the invention is to provide the choice of therapy depends on the number of white patches and how widespread they are and on the patient's preference for treatment.
Yet another aspect of the invention is to provide a latanoprost composition for the treatment for vitiligo and the drug is administered in the form of dermal applied in the form of a semisolid dosage form.
In accordance with further embodiment of the present invention, Latanoprost can be administered in the form of topical applications such as gel, cream, ointment or in any other suitable topical dosage form known to the person skilled in the art.
In accordance with the further embodiment present invention is to provide the process for preparing latanoprost composition for the treatment of Vitiligo.
5

Further aspect of the invention is the said process of preparation of Latanoprost composition for the treatment of vitiligo is cost effective and commercially viable.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is directed to a pharmaceutical compositions containing Latanoprost for the treatment of vitiligo. Prostaglandins are well known in the prior art for the treatment of vitiligo, but Latanoprost is not specifically mentioned in the prior art as effective drug for the therapy of vitiligo. Inventors of the present invention discovered that Latanoprost gel in the treatment of Vitiligo can be very effective and can be manufactured in a cost efficient manner on a commercial scale. Latanoprost can be formulated in the form of cream, gel, ointment or in any suitable topical dosage form known to the person skilled in the art that can effectively delivered the active compound.
The Latanoprost composition described herein in this invention contains inert excipients. The inert excipients includes but are not limited to polymers , buffering agents ,surface active agent, preservative, viscolizing agent, diluents, polymers, glidants, lubricants, and the like and mixtures thereof known to the person skill in the art to make suitable latanoprost pharmaceutical composition for the treatment of vitiligo.
The terms "active agent" "active pharmacological ingredient" and "drug" are used interchangeably herein to refer to Latanoprost and its salts,solvates, hydrates thereof.
The term "effective amount" as used herein means the amount of a compound that, when administered to a mammal for treating a state, disorder, condition or causing an action, is sufficient to effect such treatment or action. The "effective amount" will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.
The term "delivering" as used herein means providing a therapeutically effective amount of an active ingredient to a particular location within a host means causing a therapeutically effective blood concentration of the active ingredient at the particular location. This can be
6

accomplished, e.g., by topical, local or by systemic administration of the active ingredient to the host.
By "pharmaceutically acceptable" is meant those salts and esters which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use.
As used herein, the term "polymer" is intended to mean an agent who forms a closed chain structures used to delay the drug release. Such compounds include, by way of example and without limitation, those known to one of ordinary skill in the art.
As used herein, the term "buffering agent" is intended to mean a compound used to resist a change in pH upon dilution or addition of acid of alkali. Such compounds include, by way of example and without limitation, sodium hydroxide, potassium hydroxide, ammonium hydroxide and the like.
As used herein, the term "chelating agent" is intended to mean a compound which complexes with the metal ions in the formulation and avoids the unrequired/unwanted chemical reactions from occurring. Such compounds include, by way of example and without limitation, EDTA, and the like.
As used herein, the term "surface active agent" is intended to mean an agent that reduces the surface tension between the two different phases to distribute them to form a homogenous phase. Such compounds include, by way of example and without limitation, Poloxamer which is a water soluble Polymeric Surfactant
As used herein, the term "preservative " is intended to mean an agent that protects the formulation from degradation or detonation by avoiding oxidation, hydrolysis, or photolytic chemical reactions. Such compounds include, by way of example and without limitation, phenoxyethanol, methylparaben and the like which specifically avoids the oxidative degradation of the formulation.
7

As used herein, the term "viscolyting agent" is intended to mean an agent that increases the viscosity of the formulation by forming a cross linking structure in contact with water. Such compounds include, by way of example and without limitation, carbomer and the like.
Useful glidants include, but are not limited to, silicon dioxide, magnesium laurylsulfate or magnesium oxide can be added to the formulation to reduce interparticulate friction and to eliminate the problem associated with the flow of materials from larger to smaller apertures in the manufacturing presses. Useful lubricants include, but are not limited to, magnesium stearate, stearic acid ,polyethylene glycol, Glyceryl Behenate, calcium stearate, glyceryl monostearate etc. Binder used in this invention includes but are not limited to polyvinyl pyrrolidone, ethyl cellulose, water, gelatine, starch, pregelatinized starch etc.
Most of these excipients are described in detail in, e.g., Howard C. Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, (7th Ed. 1999); Alfonso R. Gennaro et al., Remington: The Science and Practice of Pharmacy, (20th Ed. 2000); and A. Kibbe, Handbook of Pharmaceutical Excipients, (3rd Ed. 2000), the contents of which are incorporated by reference herein. The examples of the excipients described harein should not be read as limiting scope of the invention and can be elaborated to the excipients that are suitable to make topical application of Latanoprost for the person skilled in the art..
The present invention is also directed to articles of manufacture which include the active ingredients of the invention in suitable pharmaceutical compositions packaged for distribution in conjunction with labeling or package inserts describing indications and giving dosage instructions. Packaging can be accomplished by any of a number of means utilized in the pharmaceutical industry. Other modes of packaging would be readily apparent to one skilled in the pharmaceutical packaging arts.

Taranpreet Lamba. ( Sr. Manager-IPM )
8
Dated this Eighteenth (18th) day of August, 2006