FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"CLEAR STABLE SOLUTION OF ACTIVE FRAGMENT OF BFGF FOR TREATING VITILIGO AND PROCESS OF PREPARATION THEREOF"
2. APPLICANT:
(a) NAME: IND-SWIFT LIMITED
(b) NATIONALITY: Indian Company incorporated under the
Companies Act, 1956
(c) ADDRESS: 102-103, The Summit Business Bay,
Western Express Highway, Service Road, Vile Parle (East), Mumbai-400057, Maharashtra, India,
3. PREAMBLE TO THE DESCRIPTION:
The following specification describes the invention.

Field of invention
This invention relates to a clear stable solution of active fragment of bFGF, decapeptide for treatment of vitiligo. The invention further relates to a process for preparation of the clear stable solution of active fragment of bFGF.
Background and prior art
Vitiligo is a chronic, unpredictable disease causing a loss of skin color in patches. People of all ages and from all ethnic backgrounds can develop the disease, vitiligo does not cause physical symptoms but because of its unsightly appearance, particularly on dark or tanned skin it can have considerable impact both psychologically and socially. Many ways of restoring normal color to the skin have been tried but improvement is usually short-lived. The causes of vitiligo are not yet clearly understood, so many treatments have been developed on the basis of limited scientific evidence. Around 1% of the world's population has vitiligo, a disease which causes white patches on the skin. There are a variety of treatments available, most of which are unsatisfactory.
A preparation of active fragment of bFGF, namely decapeptide, is available for the treatment. However, the product in the market is not stable, and does not provide required efficacy.
Many Patent Applications and patents viz. US6143723, AU722626 (EP0894493), DE69737143 including Indian patent Nos. IN186437, INI 85703, IN185613 for the composition of active fragment of bFGF are reported. However, the reported composition contains only three excipients, and does not mention pH required for stabilizing the active fragment. Moreover, the composition does not provide any emulsifier, or stabilizer. Combinations of bFGF with psoralens and betamethasone is also reported in Indian patent application No. 42/DEL/2004.
Object of the invention
The primary object of the present invention is to provide a stable, effective composition of the active fragment of bFGF, decapeptide for long term treatment of vitiligo by overcoming the problems of haziness and problems of stability in prior art patents.

Summary of the invention
To overcome stability problems inherent in compositions based on prior art disclosures, a stabilized clear liquid composition of the active fragment of bFGF, decapeptide is conceptualized herein and is reduced to practice by describing the composition ingredients and process for preparation thereof.
Compared to hazy and unstable liquids in market based on prior art, a clear solution which is stable for over two years is obtained by the process and composition is described herein.
Detailed description of invention
The invention is described in various embodiments below. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention.
Steareth-2 as referred in the specification mean and relate to polyethylene glycol ethers of stearyl alcohol whereas Laureth refers to polyoxyethers of Iauryl alcohol and derivatives thereof.
A stabilized clear liquid composition of the active fragment of bFGF is provided along with the process for preparation of the clear liquid for external application on the vitiligo patches. The invention provides active fragment of bFGF, decapeptide dissolved in an aqueous base. The composition involves use of acidic water and dissolving of the peptide in the acidic water. It also describes the process of mixing of surfactant in the proportion 0.0001% to 1%. The co-penetrating agent, film forming agent and the emulsifier forms a thin film on the patches, and the water in the preparation hydrates the skin, allowing retention and penetration of the decapeptide.
The proportion of water used as solvent, a hydrating and penetration supporting agent is used in 3%v/v to 50%v/v, preferably 10-30% v/v.
In an embodiment, the present invention disclose a clear stable solution of the active fragment of bFGF for treatment of vitiligo characterized in that the said clear stable solution includes a composition of active fragment of bFGF, decapeptide in aqueous

acidulated medium incorporating acetate ions using sodium acetate in solution having pH 4.5 to 5.5, co-penetrating agent in the range of 5-9%w/v, emulsifier in the range of 0.35-5.00%w/v, non-ionic surfactant in the range of 0.0001% to 1% w/v and film forming agent in the range of 5-8%v/v.
The active fragment of bFGF is decapeptide in the range of 0.05%w/v to5%w/v.
The co-penetrating agent is selected from isopropyl myristate; emulsifier is selected from the ethoxylated fatty alcohol and derivatives thereof such as Steareth-2, Laureth, preferably Steareth-2; non-ionic surfactant is selected from polyoxylated derivatives such as Tween 80; the film forming agent is selected from the group of polyhydric alcohol such as propylene glycol.
The other solvent used in the present invention is selected from lower alcohols such as isopropyl alcohol in the range of 55%-90%v/v; preferably in the range of 65-75%v/v.
The process for the preparation of clear stable solution of the active fragment of bFGF for treatment of vitiligo is described below:
i. sifting preweighed quantity of sodium acetate through #40 seive and mixing with glacial acetic acid in water;
ii. making up the volume and adjusting the pH to 4.5 to 5.5;
iii. melting Steareth-2 at a temperature not more than 45°C and dissolving in 2L of IPA;
iv. dissolving non -ionic surfactant in 3L of IPA;
v. mixing together the two solutions of step (iii) and step (iv) in IPA;
vi. mixing the film forming agent and co -penetrating agent into the mixture of step (v);
vii. dissolving 0.05%w/v to 5%w/v of decapeptide in 0.5L of acidulated water of step (ii);

viii. mixing decapeptide in acidulated water with IPA solution with constant stirring;
ix. making the volume up to 10L using additional IPA as required (about 1L), thereby making aggregate amount of IPA to 65-75%; and
x. filtering the resultant mixed solution of step (ix) to obtain a clear stable and colourless solution.
The resultant clear stable solution is filled into vials and plugged. The plug is replaced by roll on lugs before use. Stability studies are carried out at 40°C and 75% RH and the stability of the prepared composition having 2 years shelf life is confirmed. The stability data is given below in Table 1.
The composition used for treating vitiligo and the best method for preparation in the form of preferred embodiment is described herein and illustrated in the following examples.
Example 1: Composition:

SR. NO. RAW MATERIAL SPECIFICATION STD. QTY UNITS
1 DECAPEPTIDE IH 012.622 GMS
2 TWEEN 80 IP 000.065 GMS
3 STEARETH-2 IH 35.000 GMS
4 PROPYLENE GLYCOL IP 000.800 LTRS
5 ISOPROPYL MYRISTATE IP 000.800 LTRS
6 ACIDULATED WATER IH 000.500 LTRS
7 ISOPROPYL ALCOHOL Q.S. IP 010.000 LTRS
ACIDULATED WATER
1 SODIUM ACETATE IP 027.200 GMS
2 GLACIAL IP 012.000 ML

ACETIC ACID
3 PURIFIED WATER Q.S. IP 002.000 LTRS
Example 2: Process of preparation:
(A) Preparation of acidulated water
i. Preweighed quantity of sodium acetate as described is sifted through #40 seive and mixed with glacial acetic acid in water;
ii. The volume is made up and pH is adjusted to 3-6.5, preferably 4.5 to 5.5.
(B) Preparation of isopropyl alcohol (IPA) solution
iii. Melting Steareth-2 at a temperature not more than 45°C and is dissolved in 2L of IPA;
iv. Non -ionic surfactant such as Tween 80 is dissolved in 3L of IPA; and
v. The solutions of Steareth-2 and Tween 80 in IPA are mixed together.
(C) Preparation of Decapeptide solution
vi. The film forming agent such as propylene glycol and co -penetrating agent selected form isopropyl myristate are mixed with the mixture of step (v);
vii. 0.05%w/v to 5%w/v of decapeptide (as required in the formulation) is dissolved in 0.5L of acidulated water as previously prepared in step (A);
viii. The decapeptide in acidulated water is mixed with IPA solution with constant stirring;
ix. The total volume is made upto 10L using additional IPA as required (about 1L); thereby making aggregate amount of IPA to 65-75%;
x. The resultant mixed solution is filtered to obtain a clear stable solution which is filled into vials and plugged. The plug is replaced by roll on lugs before use;

xi. Stability studies are carried out at ICH IV zone and the stability for 2 years shelf life is confirmed.
Example 3 : Stability data
Conditions: 40 °C, 75% RH Label Claim: 2 mg/ml Table 1:

Months B. No. 1 B. No. 2 B. No. 3
Initial 2.2mg 2.2 2.1
One 2.2mg 2.2 2.1
Two 2.2mg 2.2 2.1
Three 2.2mg 2.1 2.08
Six 2.1mg 2.1 2.05
The product is stable up to six months.
It will be readily apparent to one skilled in the art that quantity of the excipients used and the ranges disclosed in the invention is not limited to the details of the illustrative example and that the present invention may be embodied in other specific forms without departing from the essential attributes thereof. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.

We claim,
1. A clear stable solution of the active fragment of bFGF for treatment of vitiligo characterized in that the said clear stable solution comprises a composition of active fragment of bFGF, decapeptide (0.05%w/v to 5%w/v) in aqueous acidulated medium incorporating acetate ions using sodium acetate in solution having pH 4.5 to 5.5, co-penetrating agent in the range of 5-9%w/v, emulsifier in the range of 0.35-5.00%w/v, non-ionic surfactant in the range of 0.0001% to 1% w/v and film forming agent in the range of 5-8%v/v;
wherein, the clear stable solution is prepared by a process comprising;
i. sifting preweighed quantity of sodium acetate through #40 seive and mixing with glacial acetic acid in water;
ii. making up the volume and adjusting the pH to 4.5 to 5.5;
iii. melting Steareth-2 at a temperature not more than 45°C and dissolving in 2L oflPA;
iv. dissolving non -ionic surfactant in 3L of IPA;
v. mixing together the two solutions of step (iii) and step (iv) in IPA;
vi. mixing the film forming agent and co -penetrating agent into the mixture of step (v);
vii. dissolving 0.05%w/v to 5%w/v of decapeptide in 0.5L of acidulated water of step (ii);
viii mixing decapeptide in acidulated water with IPA solution with constant stirring;
viii. making the volume upto 10L using additional IPA as required (about 1L); thereby making aggregate amount of IPA to 65-75%; and
ix. filtering the resultant mixed solution of step (ix) to obtain a clear stable and colorless solution.

2. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 1, wherein the co-penetrating agent is isopropyl myristate.
3. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 1, wherein the emulsifier selected from ethoxylated fatty alcohol and derivatives thereof.
4. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 4, wherein ethoxylated fatty alcohol selected from Steareth-2, Laureth, and derivatives thereof.
5. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 4, wherein ethoxylated fatty alcohol is Steareth-2 and derivatives thereof.
6. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 1, wherein non-ionic surfactant selected from polyoxylated derivatives.
7. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 6, wherein non-ionic surfactant is Tween 80.
8. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 1, wherein the film forming agent is polyhydric alcohol such as propylene glycol.
9. The clear stable solution of the active fragment of bFGF for treatment of vitiligo according to claim 1, wherein water is used in an amount of 10%v/v to 30%v/v.