Title of Invention

"A SYNERGISTIC COMPOSITION FOR TREATMENTOF GENERALIZED STABLE/NON-STABLE AND SEGMENTAL VITILIGO, VITILIGO, PATCHES NOT RESPONDING TO PUV-A THERAPY AND FAST SPREADING VITILIGO."

Abstract "A synergistic composition for treatment of generalized stable/non-stable and segmental vitiligo, vitiligo patches not responding to PUV-A therapy and fast spreading vitiligo". Synergistic therapies for the treatment of vitiligo are provided. The major therapies for the treatment of vitiligo a pigmentary disorder characterized by patchy depigmentation of skin are Psoralens plus UV-A, steroids, basic fibroblast growth factor (bFGF) peptide location or surgical procedures. Psoralens plus UV-A is effective in about 50% of cases, steroids or limitedly effective only in fast spreading cases of vitiligo and often reoccurs on stoppage of treatment. Surgical treatment is the last resort for vitiligo therapy, when all other therapies failed. It is limitedly effective. Basic fibroblast growth factor peptide(s) location was developed as a new mode therapy tor the treatment of vitiligo. It is effective in 80% of stable vitiligo and in segmental vitiligo. Here data are provided and demonstrated that combinatorial treatment of vitiligo by local application of bFGF peptide(s) lotion in association with psoralens and UV-A, or steroids or surgical procedures produce synergistic response and that the rate of re-pigmentation increases synergistically and more efficacious results are obtained than with any of them alone. Any combinatorial therapy comprising she local application of bFGF peptide lotion on the vitiligo patch in combination with any o;her therapy for the treatment of vitiligo appears to act synergistically.
Full Text FIELD OF INVENTION
This invention relates to a synergistic composition for treatment of generalized stable/non-stable and segmental vitiligo, vitiligo patches not responding to PUV-A therapy and fast spreading vitiligo.
BACKGROUND OF THE INVENTION
Vitiligo/leucoderma is an acquired depigmentation of skin characterized by patchy loss of pigment that becomes progressive with time. This disorder affects about 1% of the world population. Traditional therapies for vitiligo mainly include photo chemotherapy with topical/oral psoralens followed by exposure to ultra violet A radiation (PUV/A) or topical/oral steroids, PUV-A therepy is perhaps the main stay in the treatment of vitiligo. However only about 50% of cases get repigmentation. Moreover in a patient in response to PUV-A many vitiligo patches may repigment partially only and the rest of the patches ma\ remain unresponsive to PUV-A therapy even after long duration of treatment. The repigmenatation in the above therapies is a result of multiplication of melanocytes, the cells, which produce the pigment melanin in the skin. The multiplication of melanocytes in response to the above therapies occur from the margins of the vitiligo patch or at the pigmented hair follicles and their migration/spread to the vitiligo patch.
Basic fibroblast growth factor (bFGF) also known as FGF2 so named because it contains a high number of basic amino acid residutes (Lysine, Arginine and Histidine) is a potent mitogen for a variety of cell types including melanocytes. Both human and bovine bFGF were isolated and the gene expressing this product were sequenced and cloned. In addition bFGF was found to be expressed in a wide variety of tissue types including placnta, keratinocyles, fibroblasts. The bFGF or its against peptides were tested on
human volunteers in the various phases of clinical trials in India and found to be successful in repigmenting about 80% of volunteers with stable generalised vitiligo and segmental vitiligo. Patents of interest describing bFGF or against peptides and the formulation for their penetrations through intact skin include US Patent 6, 143. 723 Australian patent 722626. Indian Patents 185613. 186437.
Vitiligo is a pigmetary disorder with patchy loss of skin pigment melanin Puri N. Mojamdar M, Anew hypothesis for the etiology of vitiligo.. Acta Derm. Venerol (Stochhom), 1989. 69. 323-327 that deprivation of a mitogen(s) like basic fibroblast growth factor (bFGF) for melanocytes or its decreased level in the skin of vitiligo patients for use at unknown reason could result in the loss of melanin producing cells melanocytes in skin resulting in vitiligo. Basic fibroblast growth factor (bFGF) also known as FGF2 is a potent mitogen for variety of cell types including melanocytes. Both human and bovine bFGF have been isolated and the gene expressing tin product have been sequences and cloned. In addition bFGF has been found to be expressed in a wide variety of tissue types including pituitary, brain and adrenal gland corpusluteum. retina, kidney, placenta and keratinocytes. fibroblasts. The hypothesis that a mitogen like bFGF' may be reduced in its levels in vitiligo patch resulting in loss of melanocytes and the pigment melanin in vitiligo skin and recently from others.
SUMMARY OF THE INVENTION
According to this invention there is provided a composition for combinatorial synergistic treatment of generalized stable/non-stable and segmental vitiligo comprising of 0.02 to 5% w/w of at least one peptide selected from a group comprising of bFGF amino acids 106-115 (SEQ ID NO I), bFGF amino acids 106-120 (SEQ ID NO 5), bFGF amino acids 1-24 (SHQ.ID NO 6), SEQ H): 2. SEQ 1D:3, cyclic bFGF amino acids 106-115 (SEQ ID NOl). cyclic bFGF amino acids 106-120 (SEQ ID N05), cyclic bFGF amino acids 1-24 (SEQ ID N06), cyclic SEQ ID:2 and cyclic SEQ 1D:3 in 10-15% w/w of solvent. 10-40% w/w of glycols, and 10-40% w/w of at least one penetration enhancing agent for local application, 10-40 mgs of 8methoxy psoralens and 1-5 mgs of ncopsoralens for oral intake. After 2 hours of oral administration, vitiligo patches of the patient are exposed to morning sunlight for 5-10 minutes till the patches show erythma/red or to UV-A of 2-8 Joules/Cm'.
Further according to this invention there is provided a composition for combinatorial synergistic treatment of vitiligo patches not responding to PUV-A therapy comprising 0.02 to 5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-115 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5). bFGF amino acids 1-24 (SEQ.ID NO 6). SEQ ID: 2. SEQ ID:3, cyclic bFGF amino acids 106-115 (SEQ ID NOl). cyclic bFGF amino acids 106-120 (SEQ ID N05), cyclic bFGF amino acids 1-24 (SEQ ID N06). cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15% w/w of solvent. 10-40% w/w of glycols, and 10-40% w/w of at least one
penetration enhancing agent for local application. 10-40 mgs of 8methoxy psoralens an>i 1-5 mgs of neopsoralens for oral intake. After 2 hours of oral administration, vitiligo patches of the patient are exposed to morning sunlight for 5-10 minutes till the patches show erythma/red or to UV-A of 2-8 Joules/Cm2.
Yet further, according to this invention there is provided a composition for combinatorial synergistic treatment of fast spreading vitiligo comprising 0.02 to 5% w/w o."... least one peptide selected from a group consisting of bFGF amino acids 106-115 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5). bFGF amino acids 1-24 (SEQ.ID NO 6). SEQ ID: 2. SEQ ID:x cyclic bFGF amino acids 106-115 (SEQ ID NOl), cyclic bFGF amino acids 106-120 (SEQ ID N05). cyclic bFGF amino acids 1-24 (SEQ ID N06), cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15% w'w of solvent, 10-40% w/w of glycols, and 10-40% w/w of at least one penetration enhancing agent for lcoal application along with steroid therapy using 1 -5 mgs of any steroid such as betamethasone, which is orally given to the patient on 2 consecutive days in a week.
Still further according to this invention there is provided a composition for combinatorial synergistic treatment of vitiligo comprising 0.02 to 5% w/w of at least one peptide selected from a group comprising of bFGF amino acids 106-1 15 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5), bFGF amino acids 1-24 (SEQ.ID NO 6).SEQ ID: 2, SEQ ID:3, cyclic bFGF amino acids 106-115 (SEQ ID NOl), cyclic bFGF amino acids 106-120 (SEQ ID N05), cyclic bFGF amino acids 1-24 (SEQ ID N06), cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15% w/w of solvent. 10-40% w/w of glycols, and 10-40% w/w of at least one penetration enhancing agent for local application after surgical prodecures.
1 urther. according to this invention there is provided a composition for combinatorial syungistic treatment of vitiligo comprising 0.02 to 5% w/w of at least one peptide selected from a group comprising of bFGF amino acids 106-115 (SEQ ID NO 1). bFGF amino acids 106-120 (SEQ ID NO 5), bFGF amino acids 1-24 (SEQ.ID NO 6). SEQ ID: 2. SEQ ID:3. cyclic bFGF amino acids 106-115 (SEQ ID NOl), cyclic bFGF amino acids 106-120 (SEQ ID N05). cyclic bFGF amino acids 1-24 (SEQ ID N06), cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15% w/w of solvent. 10-40% w/w of glycols, and 10-40% w/w of at least one penetration enhancing agent for local application along with oral/local application of 10-40 mgs of psoralens/or others fhat act like psoralens plus UV-A/UV-B. or any other radiation or 1-5 mgs of any oral/local steroids such as betamethasone/any immuno modulators, in the instance immuno modulator is Eevomesol. the amount is 50-150 mgs orally/0.0001-0.0003% tacrolimus topically .
DESCRIPTION OF INVENTION
According to this invention there is provided a method for combinatorial synergistic therapy for treatment of generalized stable vitiligo and segmental vitiligo comprises local application of an effective amount of a composition comprises 0.02 to 5% w/w of at least






I CLA1M:-
1. A synergistic composition for treatment of generalized stable/non-stable and segmental vitiligo and vitiligo patches not responding to PUV-A therapy comprising of 0.02 to 5% w/w of at least one peptide selected from a group comprising of bFGF amino acids 106-115 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5). bFGF amino acids 1-24 (SEQ.ID NO 6), SEQ ID: 2, SEQ ID:3, cyclic bFGF amino acids 106-115 (SEQ ID NOI). cyclic bFGF amino acids 106-120 (SEQ ID N05). cyclic bFGF amino acids 1 24 (SEQ ID N06), cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15% w/w of solvent such as isopropyl alcohol, propyl alcohol or ethyl alcohol, 10-40% w/w of glycols such as Isopropylene glycol or polyethylene glycol and 10-40% w/w of at least one penetration enhancing agent such as proply/isopropyl or ethyl myristate or propyl'isopropyl or ethyl sterate or propyl/isopropyl or ethyl palmitate for local application. 10-40 mgs of Smethoxy psoralens and 1-5 mgs of neopsoralens.
2. A synergistic composition for trea ment of fast spreading vitiligo comprising 0.02 to 5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-115 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5), bFGF amino acids 1-24 (SEQ.ID NO 6), SEQ ID: 2, SEQ 1D:3, cyclic bFGF amino acids 106-115 (SEQ ID NOI), cyclic bFGF amino acids 106-120 (SEQ ID N05). cyclic bFGF amino acids 1-24 (SEQ ID N06), cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15%. w/w of solvent. 10-40% w/w of glycols, and 10-40%) w/w of at least one penetration enhancing agent for local application along with 1 -5 mgs of any steroid such as betamethasone.
3. A synergistic composition for treatment of vitiligo comprising 0.02 to 5% w/w of at least one peptide selected from a group comprising of bFGF amino acids 106-1 15 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5). bFGF amino acids 1-24 (SEQ.ID NO 6),SEQ ID: 2. SEQ ID:3, cyclic bFGF ammo acids 106-115 (SEQ ID NOI). cyclic bFGF amino acids 106-120 (SEQ ID N05), cyclic bFGF amino acids 1-24 (SEQ ID N06). cyclic SEQ ID:2 and cyclic SEQ ID:3 in '015%) w/w of solvent. 10-40% w/w of glycols, and 10-40% w/w of at least one penetratior enhancing agent for local application.
4. A synergistic composition for treatment of vitiligo comprising 0.02 to 5% w/w of at least
one peptide selected from a group comprising of bFGF amino acids 106-115 (SEQ ID NO 1), bFGF amino acids 106-120 (SEQ ID NO 5), bFGF amino acids 1-24 (SEQ.ID NO 6), SEQ ID: 2, SEQ ID:3, cyclic bFGF amino acids 106-115 (SEQ ID NOl), cyclic bFGF amino acids 106-120 (SEQ ID N05), cyclic bFGF amino acids 1-24 (SEQ ID NC)6), cyclic SEQ ID:2 and cyclic SEQ ID:3 in 10-15% w/w of solvent. 10-40% w/w of glycols, and 10-40% w/w of at least one penetration enhancing agent for local application along with i 0-40 mgs psoralens/or others that act like psoralens or 1-5 mgs of am steroid such as -betamethasone/ any immuno modulators, in the instance immuno modulator is Levomesol, the amount is 50-150 mgs orally/0.0001-0.0003% tacrolimus topically.

Documents:

42-del-2004-abstract.pdf

42-del-2004-claims cancelled.pdf

42-del-2004-claims.pdf

42-del-2004-complete specification (granted).pdf

42-del-2004-Correspondence Others-(20-03-2012).pdf

42-del-2004-correspondence-others.pdf

42-del-2004-correspondence-po.pdf

42-del-2004-description (complete).pdf

42-del-2004-drawings.pdf

42-del-2004-form-1.pdf

42-del-2004-form-13.pdf

42-del-2004-form-18.pdf

42-del-2004-form-2.pdf

42-del-2004-form-26.pdf

42-del-2004-form-3.pdf

42-del-2004-Petition Others-(20-03-2012).pdf

42-del-2004-petition-138.pdf


Patent Number 239632
Indian Patent Application Number 42/DEL/2004
PG Journal Number 14/2010
Publication Date 02-Apr-2010
Grant Date 28-Mar-2010
Date of Filing 09-Jan-2004
Name of Patentee ABBURI RAMAIAH
Applicant Address 137, CHARAK SADAN, VIKAS PURI, NEW DELHI, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 ABBURI RAMAIAH 137, CHARAK SADAN, VIKAS PURI, NEW DELHI, INDIA.
PCT International Classification Number A61K 31/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA