AU2005203228A1 - Synergistic Combinatorial Therapies for the Treatment of Vitiligo - Google Patents
Synergistic Combinatorial Therapies for the Treatment of Vitiligo Download PDFInfo
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Description
AUSTRALIA
Patents Act 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT Name of Applicant: Address for Service: Invention Title: Abburi Ramaiah CULLEN CO.
Level 26 239 George Street Brisbane Qld 4000 Synergistic Combinatorial Therapies for the Treatment of Vitiligo The following statement is a full description of the invention, including the best method of performing it, known to us: SField of the Invention: ci 00 ci Background of the invention: c, L, Vitiligo leucoderma is an acquired depigmentation of skin characterized by patchy loss of 0 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 therapy is perhaps the main stay in the treatment of vitiligo.
However only about 50% of cases get repigmentation. More over in a patient in response to PUV-A, many vitiligo patches may repigment partially only and the rest of the patches may remain unresponsive to PUV-A therapy even after long duration of treatment. The repigmentation 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 residues (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 placenta, keratinocytes and fibroblasts. The bFGF or its agonist 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 agonist peptides and the formulation for their penetration through intact skin include US patent 6,143,723, Australian patent 722626, Indian patents 185613,186437 and 185703.
Vitiligo is a pigmentary disorder with patchy loss of skin pigment melanin, (Ramaiah.A,Puri.N,Mojamdar M,A new hypothesis for the etiology of vitiligo,Acta 2a Derm,Venerol (Stockholm),1989,69,323-327) postulated that deprivation of a mitogen(s) like basic fibroblast growth factor (bFGF) for melanocytes or its decreased level in the skin O of vitiligo patients for as at unknown reason could result in the loss of melanin producing cells melanocytes in skin resulting in vitiligo. Basic fibroblast growth factor (bFGF) also Z 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 this product have ci been sequenced 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, oo kidney, placenta and keratinocytes, fibroblasts. The above hypothesis that a mitogen like N bFGF may be reduced in its levels in vitiligo patch resulting in loss of melanocytes and the rn pigment melanin in vitiligo skin was supported 0 Recently from studies by others (Moretti S etal Insight in to the pathogenesis of It) vitiligo,Imbalance of epidermal cytokines at sites of lesions, Pig.Cell.Res 2002,15.
0 Ci Description of Invention According to this invention there is provided a method for combinatorial synergistic therapy for treatment of generalized vitiligo and segmental vitiligo comprises local application of an effective amount of a composition 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 bFGF amino acids 1-24 (Seq ID NO Seq ID NO :2,3,4,7,and 8 as described in US patent 6143723 in the formulation as described in the US patent 6143723 along with psoralens and UV-A (PUV-A therapy)/PUV-ASOL.
The method of combinatorial synergistic therapy for treatment of vitiligo patches not responding to PUV-A therapy comprises local application of an effective amount of a composition comprising 0.02-5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-1115 (Seq ID NO bFGF amino acids 106-120 (Seq ID NO bFGF amino acids 1-24 (Seq ID N06), Seq ID NO: 2,3,4,7 and 8 as described in US patent 6143723 in the formulation as described in US patent 6143723 along with continuing the oral intake of psoralens and exposure to UV-A.
The method of combinatorial synergistic therapy for treatment of fast spreading vitiligo comprises local application of an effective amount of a composition comprising 0.02-5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-115 (Seq ID NO bFGF amino acids 106-120 (Seq ID NO bFGF amino acids 1-24 (Seq ID NO Seq ID NOs:2,3,4,7 and 8 as described in the US patent 6143723 in the formulation as described in the US patent 6143723 along with steroid therapy.
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In The method for combinatorial synergistic therapy for treatment of vitiligo comprises local Sapplication of an effective amount of composition comprising 0.02% to 5% w/w of at least N one peptide selected from a group consisting of bFGF aminoacids 106-115 (SEQ ID NO bFGF amino acids 106-120 (SEQ ID NO bFGF aminoacids 1-24 (SEQ ID NO 6), o SEQ ID: 2,3,4,7 and 8 as described in the US patent 6143723 in the formulation as N described in the US patent 6143723 along with surgical procedures. The method for Cr combinatorial synergistic therapy for treatment of vitiligo comprises local application of o the composition further comprises 10-50% w/w of solvent, 10-40% w/w of glycols, and in) 10-40% w/w of at least one penetration enhancing agent.
0 N The local application of bFGF peptide(s) in the formulation described in the US patent 6,143,723 is effective in more than 80% of cases of stable generalised vitiligo or segmental vitiligo. It is felt that the speed of repigmentation and even better out come than success rate may be accomplished if it is combined with the traditional therapies like PUV- A therapy for vitiligo. In addition bFGF peptide lotion therapy is not effective to prevent the fast spread of vitiligo and perhaps a synergistic combinatorial therapy may emerge if bFGF peptide lotion therapy is used in combination with the steroid therapy traditionally used in the case of fast spreading vitiligo. Similarly the local application bFGF peptide(s) lotion therapy may be advantageously used with any other therapy including the surgical or other therapies involving immuno modulators.
Synergistic combinatorial therapy for treatment of fast spreading vitiligo cases comprising bFGF peptide(s) in the formulation described in the US patent 6,143,723 and steroid therapy.
The bFGF peptide(s) lotion therapy is effective for stable vitiligo or segmental vitiligo but not for fast spreading vitiligo.
Steroid therapy is the only therapy available in the presently known methods of treatment to treat fast spreading vitiligo Kendel E, Vitiligo response to 02% betamethasone 17valerate in flexible collodin. Dermetologica, 1970,141,277-281). However prolonged therapy with steroid produce many side effects( Geraldiz CB, Gutierrez GT, A clinical trail of clobetasol propionate in Filipino vitiligo patients. Clinical Therapy, 1987,9,474-482, Ortonne J, Clinical Dermatol 1989,7,120-135). In addition after stoppage of treatment, the disease reoccurs. The mode of action of steroids in stopping the fast spread of vitiligo and
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Srepigmentation was thought to be brought about by its inhibitory effect on production of O auto anti bodies to melanocytes which were shown to be responsible for the fast spread of cN vitiligo macules (Han K, Chen D, Bystryn JC, Systemic steroids suppress antimelonocyte antibodies in vitilligo, J. Cutan.Med.Surg.1997,1,193-19 5 It was thought therefore oo possible that the combinatorial therapy for treatment of vitiligo with local application of N bFGF peptide(s) lotion along with oral steroids may accomplish dual goals, that is ¢ci cti In 1. Arrest of past spread of vitiligo 2. Faster repigmentation of vitiligo macules.
Description of the Accompanying drawings: Fig. 1 is the representation of vitilligo before treatment with topical bFGF peptide lotion.
Fig. 1 is the representation of vitilligo after treatment with topical bFGF peptide lotion.
Fig.2 is the representation of fast spreading vitilligo before treatment with combination of steroid and topical bFGF peptide lotion.
Fig.2 is the representation of fast spreading vitilligo after treatment with combination of steroid and topical bFGF peptide lotion.
Fig.3 is the representation of vitiligo before the treatment with combination of topical bFGF peptide lotion and PUVASOL.
Fig.3 is the representation of vitilligo after the treatment with combination of topical bFGF peptide lotion and PUVASOL.
Fig.4 is the representation of vitilligo before the treatment with topical bFGF peptide lotion and PUVASOL.
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In Fig.4 is the representation of vitilligo after the treatment with topical bFGF peptide Slotion and PUVASOL.
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CN Fig.5 is the representation of vitilligo resistant for more than a year for PUV-A before treatment with topical peptide bFGF lotion and PUV-A.
oo C Fig.5 is the representation of vitilligo resistant for more than a year for PUV-A after the n treatment with topical peptide bFGF lotion and PUV-A.
0 In Fig.6 is the representation of vitilligo resistant for more than a year for PUV-A before o the treatment with topical peptide bFGF lotion and PUV-A Fig.6 is the representation of vitilligo resistant for more than a year for PUV-A after the treatment with topical peptide bFGF lotion and PUV-A.
Fig.7 is the representation of vitilligo resistant for more than a year for PUV-A before treatment with topical peptide bFGF lotion and PUV-A Fig.7 is the representation ofvitilligo resistant for more than a year for PUVA after the treatment with topical peptide bFGF lotion and PUVA.
Fig.8 L is the representation of vitilligo after punch grafting but before start of the treatment with bFGF peptide lotion. R is the control.
Fig.8 L is the representation of vitilligo after punch grafting and after the treatment with bFGF peptide lotion for 2 months. R is the control.
EXAMPLE: 1 As a typical illustration of efficacy of bFGF peptide(s) in repigmentation of vitiligo patch of human volunteers (Fig la, Ib) were depicted. Fig la was the size of the vitiligo patch before start of treatment with bFGF peptide lotion and Ib was of the same patch after local application of the bFGF peptide(s) lotion for a period of 6 months. However the above treatment was effective in 80% of stable vitiligo and in segmented vitiligo cases (See Table -1,2 for more details).
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In Z Patents of interest describing bFGF or agonist peptides derived from it for use as Spigmentary agents include US Patent 6,143,723, Australian Patent NO: 722626, Indian N Patents 185613,186437 186703.
o0 The local application of bFGF peptide(s) in the formulation described in the US patent c 6,143,723 is effective in more than 80% of cases of stable generalised vitiligo or segmental en vitiligo. It is felt that the speed of repigmentation and even better out come than O success rate may be accomplished if it is combined with the traditional therapies like PUV- 'i A therapy for vitiligo. In addition bFGF peptide(s) lotion therapy is not effective to prevent o the fast spreading of vitiligo and perhaps a synergistic combinatorial therapy may emerge C if bFGF peptide lotion therapy is used in combination with the steroid therapy traditionally used in the case of fast spreading vitiligo. Similarly the local application bFGF peptide(s) lotion therapy may be advantageously used with any other therapy including the surgical therapies.
EXAMPLE: 2 The mode of action of steroids in stopping the fast spread of vitiligo and repigmentation was thought to be brought about by its inhibitory effect on production of auto anti bodies to melanocytes which were shown to be responsible for the fast spread of vitiligo macules (Han K, Chen D, Bystryn JC, Systemic steroids suppress antimelonocyte antibodies in vitilligo, J. Cutan.Med.Surg.1997,1,1 9 3 -1 9 5 It was thought therefore possible that the combinatorial therapy for treatment of vitiligo with local application of bFGF peptide(s) lotion along with oral steroids may accomplish dual goals, that is 3. Arrest of past spread of vitiligo 4. Faster repigmentation of vitiligo macules.
That this happens was shown in a clinical trial on human volunteers. The above twin objectives were accomplished. A typical case of such treatment was shown in Fig 2a, 2b.
Fig 2a describes two vitiligo patches at the start of treatment of oral steroids, while 2b describes the same patches at the end of 3 months of treatment with oral steroids while at 7
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In Sthe same time bFGF peptide(s) lotion was applied locally once a day on the lower vitiligo O patch for the duration of intake of oral steroids. It can be clearly seen that there was faster cN repigmentation where bFGF peptide(s) lotion was applied as compared to the upper vitiligo patch where there was no application of bFGF peptide(s) lotion. The arrest of the fast o spread of the disease was accomplished to the same extent of 88% at the end of 6 months ci of treatment with oral steroids and the result was not altered by the local application of en bFGF peptide(s) lotion (See table 3 for more details) 0 At the end of 3 months of combinatorial treatment with steroids and local application of bFGF peptide(s) lotion more than 3 fold more patients got pigmented to a marked extent ci than with steroid alone (See Table 4 for more details). The percentage of volunteers who had moderate and marked rate of repigmentation with combinatorial therapy at the end of three months of treatment is twice than with the steroid therapy alone.
Synergistic combinatorial therapy for treatment of stable vitiligo comprising-local application of bFGF peptide(s) in the formulation described in the US patent 6,143,723 and oral psoralens plus application of UV-A.
The major or main stay of treatment of stable vitiligo all over the world is at present psoralens and UV-A therapy (Mofty EL, A preliminary clinical report on the treatment of leucoderma with ami Majus Linn. Jroy.Egypt.Med.Assoc, 1948,651-660, Mofty EL, In Vitilligo, and psoralens 1968,Pregman Press Oxford, Ortonne JP, Bose Sk, Vitilligo, Wheree do we stand, Pig.Cell.Res 1993,6,61-72). However it is only partially effective (Westerhof Wiete, Ludmila Nieuwebor-krobotova, Traeatment of vitilligo with UV-B radiation VS topical psoralen Plus UV-A. arch.Dermatol 1997,1525-1528) and requires long duration of treatment. In addition it has many side effects particularly on liver and the risk of cancer in the Caucasian skin type 11 and 111 population (Henseleer T, Cristopher E, Honingsmann H, Wolff K, Skin tumors in European PUV-A study, 8year follow up of 1643 patients treated with PUV-A for psoriasis J.Am.Acad. Dermatol 1997,16,108-116, Ster RS, Lard M, The carcinogenic risk of treatment for severe psoriasis photochemotherapy follow up study.1994, 73,2759-2764). Therefore there is indeed a need to reduce the a) Duration of the treatment b) To increase success rate c) To treat cases non responsive to PUV-A therapy.
O 8 ci 0 The mechanism of action of psoralens and UV-A in repigmentation of vitiligo patches is
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still an enigma. Psoralens by themselves are ineffective in treating vitiligo unless followed by exposure of skin to UV-A (Gupta AK, Anderson TF, Psoralen photochemotherapy.
oo J.Amer.Acad.Dermatol 1987,17,703-34). The absorption maxima of psoralens lie in the S210 330 nm range (Harbar LC, Bickeers. DR," Photosensitivity Diseases" 1 st edition en Philadelphia: W.B.Saundeers 1981,PP45-55) and the action spectrum of ingested psoralens is probably in the range of 320 -335 nm (Flemming MG, Brody N, Biological tC) effectiveness of blak light fluorescent lamps for PUV-A. J.Amer.Acad.Dermatol, o 1985,12,894). The psoralens induce skin photosensitization and involves inter-chelation of ,I psoralens with the DNA of the cell, which leads eventually to the death of that cell. That this is true in the case of melanocytes also was shown by exposure of melanocytes in culture to PUV-A (KaoC, Yu H, Comparison of the effect 8-methoxy psoralen plus UV-A on human melonocytes in vitilligo vulgaris in-vitro.J.Invest.Dermatol. 1992,98,734-40).
How to explain then the beneficial effects of PUV-A in increasing the proliferation of melanocytes, their migration to vitiligo patches and thus repigment vitiligo macules? The main target of PUV-A is the epidermis, which receives UV-A radiation. This could kill keratinocytes of the epidermis. The cellular contents of keratinocytes can then leak and stimulate the proliferation of the adjacent melonacytes. The cellular contents of keratinocytes include many mitogens to melanocytes in addition to bFGF (Halban R, Tyrrell L, Longely J, Yanden Y, Rubin J, Ann.NY.Acad.sci 1993,680,290-300). That the serum from successfully treated vitiligo patients with PUV- A stimulates the proliferation of melonacytes from normal untreated vitiligo patients was shown-in 1989 (Ramaiah.A, Puri.N, Mojamdar M, A new hypothesis for the etiology of vitiligo, Acta Derm, Venerol (Stockholm), 1989,69,323-327).
In addition it was shown that the melonacytes from successfully treated vitiligo patients grow with less generation time than the melanocytes from the untreated normal individuals ((Ramaiah.A,Puri.N,Mojamdar M,A new hypothesis for the etiology of vitiligo,Acta Derm,Venerol (Stockholm); 1989,69,323-327).
These results indicated that the combinatorial treatment of vitiligo comprising local application of bFGF peptide(s) lotion with ora! psoralens plus UV-A might act synergistically and produce fasteegqi pation than with 4eher of them alone.
7, 9 0 Z EXAMPLE: 3 ci That indeed the combinatorial therapy for treatment ofvitiligo comprising local application oQ of bFGF peptide(s) lotion and PUV-A works synergistically could be seen in the typical N pictures shown in Fig 3a, 3b and 4a, 4b.The 3a and 4a are the pictures of two volunteers a before the combinatorial treatment, while 3b and 4b are the pictures of the same volunteers O respectively at the end of 3 months of combinatorial treatment where the right hand of each Lfl volunteer was in addition treated with the local application of bFGF peptide(s) lotion. As o can be seen from the pictures, the right hands of both the volunteers treated in addition ci with the local application of bFGF peptide(s) lotion repigmented many times more than that of the left hands of both the volunteers, which were treated with the PUV-A therapy only. The data presented in Table 4 clearly indicate that 7 volunteers treated with combinatorial treatment with bFGF peptide(s) lotion and PUV-A had marked repigmentation in 3 months compared to only one with PUV-A. The percentage of volunteers who had moderate to marked rate of repigmentation with the combinatorial therapy at the end of three months is about twice than the number with PUV-A therapy alone (See Table 5 for details).
Synergistic combinatorial therapy for treatment of vitiligo not responding to PUV-A comprising local application of bFGF peptide(s) and PUV-A therapy.
In response to PUV-A therapy, less than 20% of vitiligo patches repigment fully, 30-40% of vitiligo patches repigment partially (Westerhof Wiete, Ludmila Nieuwebor-krobotova, Treatment ofvitilligo with UV-B radiation VS topical psoralen Plus UV-A. arch. Dermatol 1997, 1525-1528). The vitiligo patches of volunteers, who did not respond PUV-A therapy even after prolonged treatment for a year or more were selected for the combinatorial therapy of local application of bFGF agonist peptide(s) lotion with the continued PUV-A therapy.
EXAMPLE: 4 The combinatorial therapy was very successful in repigmenting vitiligo patches with in 3 months which were unresponsive for more than year to PUV-A therapy .The typical results i Z were shown in fig 5a, 5b and 6a, 6b and 7a, 7b. The rate of repigmentation is indeed O remarkable in 5a, 5b and 6a, 6b.It is also remarkable that the vitiligo patch in the palm c which normally never responds to PUV-A therapy even after prolonged duration responded well to combinatorial therapy of bFGF peptide(s) lotion and PUV-A. The response to oo combinatorial therapy was shown in more than 90% of cases (See Table 6 for details).
ci Cr The results presented here were not exhaustive. The combinatorial therapy with local c- application of bFGF peptide(s) in the formulation described in the US patent 6,143,723 can i) be applied to almost any other therapy that are now in the market for the treatment of o various types of vitiligo with synergistic effects similar to what was observed in the cases ci described above. The bFGF peptide(s) in the formulation may be applied locally not only in the form of a lotion but also in any other form like gel /ointment/cream with similar results.
Synergistic combinatorial therapy for the treatment of vitiligo comprising punch graft surgical procedure/or other surgical procedures followed by the local application of bFGF peptide(s).
Surgical procedures as mentioned earlier are resorted to as the last chance for the treatment of vitiligo patches. They include thrish grafting, expansion of autologus melanocytes in culture and their application on to derm-abraded vitiligo patch, autologus expansion of keratinocytes and melaonocytes in culture in the form of a multi cell layered sheets and their application on the derm-abraded vitiligo patches, or punch grafting of pigmented autologus skin on to the derm-abraded vitiligo patches. In all these cases, after the surgical procedures, the vitiligo patches were surgical bandaged with appropriate antibiotic regimen for the healing of the wounds. The wounds heal with in week or so. Then the local application of the bFGF peptide(s) in the formulation described in the US patent 6,143,723 was done for 3 months. This results in faster repigmentation uniformly.
EXAMPLE: The photographs 8a and 8b describe the synergistic effect on increasing the rate of repigmentation in 8b where the local application of the bFGF peptide(s) in the formulation was done following the punch graft surgical procedure.
2005203228 20 Jul12005 Table11 I Effect of Local Application or Active P'ept)ide on [(epiginentationi of all types. Of Vitiligo Patches of Volunteers Quality of Improvement Marked Moderate Minimal Nil At 12 weeks 15 31 52 0 of total TEnd of treatmnent 15.3 31,6 29 53 .20 0 of total significant repigmentation at end of treatment 2005203228 20 Jul 2005 Table 2 Effect of Local Application of Active Peptide on Repignlentation of patches of Segmental Vitiligo of Volunteers Quality of At 12 weeks of total End of of total significant repigmentation Improvement treatment at end of treatment 16 83 Moderate Minimal 34.7 60 8 14 4 17.4 2005203228 20 Jul 2005 1 Table 3 Disease Activity of Vitiligo in Patients treat with cither OMP of beta methasone or together with local application of active peptide R No. orf patients where the disease was arrtcted with time Treatment Regimen I At 3 months At 6 months Active Peptide -OMP 12 75% I 14 87.5% OMPAlone 12I 75% 14 87.5% 2005203228 20 Jul 2005 Table 4 Effect of oralminipulse of beta methasone and local application of active peptide on repigmentation of vitiligo patches of volunteers with time 2005203228 20 JulI2005 Effect of PUV-A Sol and local application of active peptide on repigmentation of vitiligo patches of volunteers with time TetetRgmnAt 3 mionths At 6 months Minimal ModertV Marked Minimal Moderate Marked Active Peptide PUV-A Sol 6 5 7 2 4 12 PUV-A Sol Alone 11 6 7 5 6 2005203228 20 Jul 2005 Table-6 Clinical Trials on 'bvImniat oC, '1JVA rcsistanmL Y .il Mclies hycomiution with local application u[ bFlGF peptide(s)
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1)01= Duration of the disease P .11 =am.l h> iistory is posmitive whrn is gie All liC Ci~i% iImIiipCI 1 10n 1tri 3s 110i relli iii fie restinris of iIeclliricil
Claims (5)
1. A method for combinatorial synergistic therapy for treatment of generalized stable 0o vitiligo and segmental vitiligo comprising local application of an effective amount of a composition comprising 0.02 to 5% w/w of at least one peptide selected from CCr a group consisting of bFGF amino acids 106-115 (Seq ID NO bFGF amino acids o 106-12 (Seq ID NO bFGF amino acids 1-24 (Seq ID NO 6) and the other seq It IDS NOS: 2,3,4,7,and 8 as described in the US patent 6143723 in the formulation o described in the US patent 6143723 along with psoralens and UV-A (PUV-A 0 therapy)/PUVASOL
2. A method for combinatorial synergistic therapy for treatment of vitiligo patches not responding to PUV-A therapy comprising local application of an effective amount of a composition comprising 0.02-5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-115 (Seq ID NO bFGF amino acids 106-120 (Seq ID NO bFGF amino acids 1-24 (Seq ID NO Seq IDS NOS: 2,3,4,7,and 8 asdescribed in the US patent 6143723 in the formulation in the formulation as described in US patent 6143723 along with PUV-A therapy.
3. A method for combinatorial synergistic therapy for treatment of vitiligo patches not responding to PUV-A therapy comprising local application of an effective amount of a composition comprising 0.02-5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-115 (Seq ID NO bFGF amino acids 106-120 (Seq ID NO bFGF amino acids 1-24 (Seq ID NO Seq IDS NOS: 2,3,4,7,and 8 asdescribed in the US patent 6143723 in the formulation in the formulation as described in US patent 6143723 along with oral steroid therapy.
4. A method for combinatorial synergistic therapy for treatment of vitiligo patches not responding to PUV-A therapy comprising local application of an effective amount of a composition comprising 0.02-5% w/w of at least one peptide selected from a group consisting of bFGF amino acids 106-115 (Seq ID NO bFGF amino acids
106-120 (Seq ID NO bFGF amino acids 1-24 (Seq ID NO Seq IDS NOS: 2,3,4,7,and 8 as described in the US patent 6143723 in the formulation as described in US patent 6143723 along with surgical procedures. ci A method for combinatorial synergistic therapy for treatment of vitiligo patches oo not responding to PUV-A therapy comprising local application of an effective cI amount of a composition comprising 0.02-5% w/w of at least one peptide selected en from a group consisting of bFGF amino acids 106-115 (Seq ID NO 1),bFGF amino o acids 106-120 (Seq ID NO 5),bFGF amino acids 1-24 (Seq ID NO Seq IDS NOS: itn 2,3,4,7,and 8 as described in the US patent 6143723 in the formulation as 0 described in US patent 6143723 along with oral/topical application of Ci psoralens/others that act like psoralens plus UV-A/UV-B or any other radiation that help in pigmentation or oral /local steroids or any immuno modulators. Abburi Ramaiah By the patent attorneys for the applicant CULLEN CO. Date: 20 July 2005
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2019142124A1 (en) * | 2018-01-17 | 2019-07-25 | Cadila Healthcare Limited | Pharmaceutical compositions for treatment of vitiligo |
| WO2023131829A1 (en) * | 2022-01-05 | 2023-07-13 | Ramakrishna Reddy Isanaka | A formulation for treatment of pigmentary disorders |
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| US6143723A (en) * | 1996-05-20 | 2000-11-07 | Ramaiah; Abburi | Pigmentory agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2019142124A1 (en) * | 2018-01-17 | 2019-07-25 | Cadila Healthcare Limited | Pharmaceutical compositions for treatment of vitiligo |
| WO2023131829A1 (en) * | 2022-01-05 | 2023-07-13 | Ramakrishna Reddy Isanaka | A formulation for treatment of pigmentary disorders |
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