Claims:We Claim:
1. An antidandruff composition comprising
(i) an azole compound;
(ii) aminoacid based silver salt;
(iii) surfactants;
wherein the ratio of azole: amino acid based silver salt: surfactant varies from 1:0.04: 15 to 1:0.05:50 to synergistically enhance the antidandruff efficacy of an azole compound.

2. An antidandruff composition as claimed in preceding claim 1 having antidandruff activity within 30 mins.

3. An antidandruff composition as claimed in anyone of preceding claims 1 or 2 wherein said surfactants are selected from at least one or more of anionic, amphoteric, non-ionic or mixtures thereof.

4. An antidandruff composition as claimed in anyone of preceding claims 1-3 comprising azole compounds in an amount the range of from 0.1 to 5% by weight, more preferably in an amount in the range of from 0.1 to 3 % by weight, more preferably in an amount in the range of from 0.3 to 2% by weight.

5. An antidandruff composition as claimed in anyone of preceding claims 1-4 comprising amino acid based silver salts preferably from negatively charged acidic aminoacids, hydrophobic non-polar amino acids and more preferably from hydropobic non-polar aminoacids in the levels of in an amount atleast 0.01% .
6. An antidandruff composition as claimed in anyone of preceding claims 1-5 wherein said at least one or more surfactants are present in the levels of range from 5% to 35% ,preferably from 8% to 20% more preferably from 10% to 15% and are selected from anionic, amphoteric , nonionic surfactants or mixtures thereof.

7. A process for the preparation of the antidandruff composition as claimed in anyone of preceding claims 1-6 comprising the steps of
providing an azole compound, aminoacid based silver salt; surfactants; in the ratio of azole: amino acid based silver salt: surfactant from 1:0.04:15 to 1:0.05:50 and obtaining therefrom said antidandruff composition that synergistically enhances the antidandruff efficacy of an azole compound.

8. A process for the preparation of antidandruff composition as claimed in claim 7 that is surfactant based comprising the steps of
i. adding at least one or more surfactants selected from anionic, amphoteric/ zwitterionic and non-ionic surfactants or mixtures thereof along with the required quantity of salicylic acid and azole compound in deionized water followed by heating the mixture to a temperature in the range of 70-90 Deg C and mixing well until a homogenous solution is obtained;
ii. dispersing the acrylate polymer followed by adding deionized water equal or greater than 10 times the quantity of acrylate polymer and mixing under stirring conditions until the acrylate polymer is dispersed and adding the dispersed acrylate polymer obtained in step (ii) to the composition obtained in step (i);
iii. dispersing the Guar hydroxypropyltrimoniumchloride followed by adding deionized water equal to or greater than about 10 times the quantity of Guar hydroxypropyltrimoniumchloride and mixing under stirring conditions until the Guar hydroxypropyltrimoniumchloride is dispersed;
iv. adding the dispersed Guar hydroxypropyltrimoniumchloride solution obtained in step (iii) to the solution added in step (ii);
v. adding silicone emulsion and amino acid based silver salt to the solution obtained in step (iv) above and mixing the resulting mixture thoroughly until a homogenous solution is obtained;
vi. optionally, adding other hair benefiting ingredients under stirring conditions with moderate agitation to prevent heavy aeration until the composition is uniform.

Dated this the 24th day of September, 2015 Anjan Sen
Of Anjan Sen and Associates
(Applicants Agent)
, Description:FIELD OF THE INVENTION
The present invention provides for antidandruff formulation/composition wherein the antidandruff efficacy of an azole compound is synergistically enhanced in the presence of surfactant and amino acid based silver salt, when taken in selective ratios. The formulation/composition of the present invention thus advantageously can be provided in various surfactant based personal care compositions to effectively treat dandruff conditions in a subject in a short span of time lesser than 30 minutes.
BACKGROUND ART
The antimicrobial effect of silver ions is well known. An excellent product containing silver sulphadiazine is known and widely available and based on the belief that resistant organisms may still arise and that it would be advantageous to include a second antimicrobial agent along with the silver salt, following which it was found that including an azole derivative with a silver salt boosted the antibacterial and antifungal effect against several important pathogenic organisms. The use of azole derivatives enables the use of composition against topical fungal infections as well as against topical bacterial infections. There are several prior arts employing silver or azole either alone or in combination with other ingredients actives towards variety of organisms.
JP2011178731A2 principally teaches N-acetylmethionine silver complex, a liquid composition containing N-acetylmethionine silver complex and a germicide composition containing N-acetylmethionine silver complex. The composition of this prior art is used as an antifungal agent apart from being used as a germicide to annihilate microorganisms, such as bacteria, mold, and algae. The patent describes about preparing the N-acetylmethionine silver complex in the liquid form which is also stable and has long lasting activity.
US6939566 in relating to a microbiocidal composition comprising a silver salt or colloidal silver together with at least one organic chelating moiety formed from an alpha amino acid does not teach any azole for its activity.
US4803066 relates to a pharmaceutical composition for topical administration comprising a synergistic mixture of an antimicrobial silver compound and an antimicrobial azole compound or a pharmaceutically acceptable acid addition salt thereof in the weight ratio of 10:1 to 1:10 in combination with a topically acceptable carrier. The silver compound of interest is silver sulphadiazine and silver sulphamides. The topical acceptable carrier is reported to have commonly used ingredients like fatty alcohols, emulsifying agents and non-ionic surfactants. Even though the patent describes about the synergy about silver compound and azole, the composition is not directed to anti bacterial/ anti microbial efficacy attainable within a short span of time.
US20060115440 discloses a personal care composition, comprising silver dihydrogen citrate and a physiologically acceptable medium and also provides for hair care compositions and methods that confer an anti-dandruff effect, particularly by combining silver dihydrogen citrate with other antimicrobials such as zinc pyrithione, octopirox, climbazole, sulfur, imidazole derivatives such as ketoconazole and itraconazole or salicylic acid.
US8574608B2 discloses a antimicrobial polymeric compositions containing surfactants which can be used as coating. This prior art particularly relates to anionic surfactants and anionic polyelectrolytes that are monodentate ligands for cations such as silver or sodium ions and also surfactants that form reverse micelles and reverse micro emulsions. But anti microbial efficacy of the composition could be realized only after 12 or 24 hours of leave on application of the composition .
Metal complexes as anti microbials from the book A search for Anti bacterial agents( www. Intechopen.com) in Chapter 5 reveals azoles in combination with various metal ions as antimicrobial active and antifungal actives.
Molecules, 2010, 15, 2499-2508 teaches imidazolidin-2-ylidene silver complexes found to display effective antimicrobial activity against a series of bacteria and fungi though it does not teach any antidandruff activity.
Inorg.Chem.2003, 42, 8028-8032 deals with an entirely different silver compound that is water-soluble anionic silver 2-mercaptonicotinate complex having effective antibacterial and antifungal properties and also discloses gold-phosphine complexes involving imidazole ligands that reveals a very similar spectrum of selective activities against Gram-positive Bacteria but does not disclose any selective antidandruff activity.
While it is evident from the state of the art that there are several azole based antimicrobial compositions there is still a need in the art to explore such compositions further that are specifically active against dandruff to treat dandruff conditions in short application time when applied to find diverse end use/ application while at the same time being stable as a product in surfactant based formulation/composition to show its desired activity.

OBJECTS OF THE INVENTION
It is thus the primary object of the present invention to provide for formulation/composition for treating dandruff conditions in a subject which would be effective in less contact time wherein the efficacy of an azole compound would be synergistically enhanced in the presence of the ingredients of the formulation/ composition. It is another object of the present invention to provide for formulation/compositions that is azole based and would be efficacious against dandruff causing organism for topical application that would also be effective in reduced application time to deliver superior antidandruff efficacy in surfactant based personal care compositions such as shampoo, rinse–off conditioners and the like.
It is yet another object of the present invention to provide for said formulation/composition and a process for its preparation thereof that would be stable on shelf without any loss of anti-dandruff activity.

SUMMARY OF THE INVENTION
Thus according to the basic aspect of the present invention there is provided an antidandruff formulation/composition comprising
(i) an azole compound;
(ii) aminoacid based silver salt;
(iii) surfactants; wherein the ratio of azole: amino acid based silver salt: surfactant varies from 1:0.04: 15 to 1:0.05:50 to synergistically enhances the antidandruff efficacy of an azole compound.
Advantageously, said antidandruff composition of the present invention shows antidandruff activity within 30 mins.
According to another preferred aspect of the present invention there is said antidandruff formulation/composition wherein said surfactants are selected from at least one or more of anionic, amphoteric, non-ionic or mixtures thereof.
The present Invention relates to the development of antidandruff formulation/composition which is efficacious within 30 minutes contact time where in the antidandruff efficacy of the azole compound is significantly improved by the presence of surfactant and amino acid based silver salt, comprising in addition to water
(i) an azole compound
(ii) aminoacid based silver salt
(iii) atleast one surfactant selected from anionic, amphoteric, non-ionic and mixtures thereof
(iv) with or without other conditioning benefit agents
wherein the ratio of Azole to Silver to surfactant is from 1:0.04:15 to 1:0.05:50.
It is thus the surprising finding of the present invention that the antidandruff efficacy of an azole compound is synergistically enhanced in the presence of surfactant and amino acid based silver salt when taken in selective ratios of Azole to Silver to surfactant of from 1:0.04:15 to 1:0.05:50, which is significantly efficacious within 30 minutes contact time.
According to another aspect of the present invention there is provided said antidandruff composition comprising azole compounds in an amount of from 0.1 to 5% by weight, more preferably in an amount in the range of from 0.1 to 3 % by weight, more preferably in an amount in the range of from 0.3 to 2% by weight.
According to yet another aspect of the present invention there is provided said antidandruff composition comprising amino acid based silver salts preferably from negatively charged acidic amino acids, hydrophobic non-polar amino acids and more preferably from hydropobic non-polar aminoacids in the levels of in an amount atleast 0.01%.
According to another aspect of the present invention there is provided said antidandruff composition wherein said at least one or more surfactants selected from anionic, amphoteric, non-ionic and mixtures thereof are present in the levels of range from 5% to 35%, preferably from 8% to 20% more preferably from 10% to 15% and are selected from anionic, amphoteric, nonionic surfactants or mixtures thereof.
According to another aspect of the present invention there is provided a process for the preparation of said antidandruff composition comprising the steps of
providing an azole compound, amino acid based silver salt, surfactants, in the ratio of azole: amino acid based silver salt: surfactant from 1:0.04: 15 to 1:0.05:50 and obtaining therefrom said antidandruff composition that synergistically enhances the antidandruff efficacy of an azole compound.

Preferably a process for the preparation of antidandruff composition is provided that is surfactant based comprising the steps of
(i) adding at least one or more surfactants selected from anionic, amphoteric/ zwitterionic and non-ionic surfactants or mixtures thereof along with the required quantity of salicylic acid and azole compound in deionized water followed by heating the mixture to a temperature in the range of 70-90 Deg C and mixing well until a homogenous solution is obtained;
(ii) dispersing the acrylate polymer followed by adding deionized water equal or greater than 10 times the quantity of acrylate polymer and mixing under stirring conditions until the acrylate polymer is dispersed and adding the dispersed acrylate polymer obtained in step (ii) to the composition obtained in step (i);
(iii) dispersing the Guar hydroxypropyltrimoniumchloride followed by adding deionized water equal to or greater than about 10 times the quantity of Guar hydroxypropyltrimoniumchloride and mixing under stirring conditions until the Guar hydroxypropyltrimoniumchloride is dispersed;
(iv) adding the dispersed Guar hydroxypropyltrimoniumchloride solution obtained in step (iii) to the solution added in step (ii);
(v) adding silicone emulsion and amino acid based silver salt to the solution obtained in step (iv) above and mixing the resulting mixture thoroughly until a homogenous solution is obtained;
(vi) optionally, adding other hair benefiting ingredients under stirring conditions with moderate agitation to prevent heavy aeration until the composition is uniform.
The present invention is described hereunder in greater details in relation to the non-limiting exemplary illustrations.
DETAILED DESCRIPTION OF THE INVENTION
As discussed hereinbefore the present invention provides for antidandruff formulation/composition wherein the antidandruff efficacy of an azole compound was surprisingly found to be synergistically enhanced in the presence of surfactant and amino acid based silver salt, when taken in selective ratios, and which synergy was found to be established based on the log difference values recorded by time-kill assay method. Log difference is calculated as follows Log10 (Initial count)-Log10 (x time interval)= Log10 reduction (African Journal of Microbiology Research Vol. 7(46), pp. 5248-5252, 21 November, 2013) . Advantageously, the formulation/ composition of the present invention can be provided in surfactant based various personal care compositions to effectively treat dandruff conditions in a subject.
The time-kill method has been used widely for the evaluation of new antimicrobial agents and allows the determination of whether an agent produces concentration-dependent killing (where the extent of killing increases with increased drug concentrations) As is well known to a person proficient in micro biological evaluation, a decrease in CFU per milliliter =2 -log10-unit in the presence of added components is defined as synergy between the combinations of agents/ components as per time kill kinetics. (Clinical Microbiology Reviews pg. 268-280 Vol17, No.2, April 2004).

Azoles
An important group of active ingredients that are currently being used in the treatment of dandruff are antimycotics for topical and systemic administration from the group of the azoles. Anti-dandruff agents known in the art are climbazole as well as further azoles such as, for example, benzimidazole, benzothiazole, bifonazole, butaconazole nitrate, clotrimazole, croconazole, eberconazole, econazole, elubiol, fenticonazole, fluconazole, flutimazole, isoconazole, ketoconazole, lanoconazole, metronidazole, miconazole, neticonazole, omoconazole, oxiconazole nitrate, sertaconazole, sulconazole nitrate, thioconazole, as well as diazoles and triazoles, such as, for example, terconazole and itraconazole, as well as any desired combinations of the mentioned azoles.
The composition of present invention contains azoles in an amount the range of from 0.1 to 5% by weight, more preferably in an amount in the range of from 0.1 to 3 % by weight, more preferably in an amount in the range of from 0.3 to 2% by weight.
Amino acid based Silver salt
Since ancient times, the silver ion has been known to be effective against a broad range of microorganisms. Silver is active at very low concentrations and is reported to have low toxicity.It has been found that the silver–oxygen bonding properties rather than chiral helical or achiral polymer structure play a role in exhibiting antimicrobial activities. The antimicrobial acitivity of Silver–oxygen bonding complex is due to silver ion itself i.e. due to direct interaction of silver ion and biological ligands such as protein, enzymes and membrane. Commonly used silver salts while are silver nitrate, silver sulphadiazine, silver benzoate, silver oxide, Silver bonded complexes of 2- mercaptonicotinic acid, 2- mercaptobenzoic acid etc., the synergistic enhancement of the composition of the present invention is attained only by the amino acid based silver salts such as Silver L-histidine complex, Silver cysteine complexes, Silver (I) complexes of glycine, alanine,valine, leuicine,iso leuicine,serine,threonine, aspartic acid,proline, phenylalanine, aspartic acid, phenyl alanine, glutamic acid, tyrosine, aspargine, tryptophan, glutamine, methionine etc. Silver compound dosage in composition beyond a particular level is not practiced since efficacy is achieved at very low dose levels as well as the cost is very high in addition to its nature to affect the aesthetics of the composition. In addition, there are regulations pertaining the use of silver salts for cosmetic applications wherein the recommended dose level for silver salt is 0.2% (ref. AnnexureIII1223/2009 List of substances which cosmetic product must not contain except subject to restriction laid down ref.no.48.EU cosmetic directive-which is a Internal cosmetic regulatory body set up by European union
The formulation/composition of present invention contains amino acid based silver salt selected from negatively charged acidic amino acids, positively charged basic amino acids, non charged hydrophilic polar amino acids, hydrophobic non-polar amino acids preferably from negatively charged acidic aminoacids , hydrophobic non-polar amino acids and more preferably from hydropobic non-polar amino acids in an amount of atleast 0.01% .
Surfactant
The preferred anionic surfactants for use in the shampoo compositions include but not limited to ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, and combinations thereof.
Other anionic surfactants suitable for use in the shampoo compositions include but not limited to the succinates, examples of which include disodium N-octadecylsulfosuccinnate; disodium lauryl sulfosuccinate; diammonium lauryl sulfosuccinate; tetrasodium N-(1,2- dicarboxyethyl)-N-octadecylsulfosuccinnate; diamyl ester of sodium sulfosuccinic acid; dihexyl ester of sodium sulfosuccinic acid; and dioctyl esters of sodium sulfosuccinic acid, and combinations thereof.
Suitable amphoteric or zwitterionic surfactants for use in the shampoo compositions herein include those which are known for use in hair care or other personal care compositions.
Amphoteric / Zwitterionic surfactants suitable for use in the shampoo compositions are well known in the art, and include those surfactants broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic water solubilizing group such as carboxy, sulfonate, sulfate, phosphate, or phosphonate. Preferred amphoteric / zwitterionic surfactants for use in the present invention include cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate, lauroamphodiacetate, and mixtures thereof. Zwitterionics such as betaines are preferred.
The nonionic surfactant may be selected from Amides, including alkanol amides, which are the condensation products of fatty acids with primary and secondary amines or alkanolamines to yield products of the general formula:

wherein RCO is a fatty acid radical and R is C8-20 ; X is an alkyl, aromatic or alkanol (CHR'CH2OH wherein R' is H or C1- 6 alkyl) ; Y is H. Suitable amides include, but are not limited to cocamide, lauramide, oleamide and stearamide. Suitable alkanolamides include, but are not limited to, cocamide DEA, cocamide MEA, cocamide MIPA, isostearamide DEA, isostearamide MEA, isostearamide MIPA, lanolinamide DEA, lauramide DEA, lauramide MEA, lauramide MIPA, linoleamide DEA, linoleamide MEA, linoleamide MIPA, myristamide DEA, myristamide MEA, myristamide MIPA, Oleamide DEA, Oleamide MEA, Oleamide MIPA, palmamide DEA, palmamide MEA, palmamide MIPA, palmitamide DEA, palmitamide MEA, palm kernelamide DEA, palm kernelamide MEA, palm kemelamide MIPA, peanutamide MEA, peanutamide MIPA, soyamide DEA, stearamide DEA, stearamide MEA, stearamide MIPA, tallamide DEA, tallowamide DEA, tallowamide MEA, undecylenamide DEA, undecylenamide MEA and PPG-2 hydroxyethyl coco/isostearyamide.The composition may also contain amino acid based surfactants sold under the trade name Amilite GCK-12 , Amilite ACS-12 by Ajinomoto Co.Inc, Sodium cocoyl glutamate, Sodium cocoyl glycinate, Sodium cocoyl taurate,sodium lauryl sarcosiante,Sodium cococyl apple aminoacids,Sodium lauroyl oat amino acids,Sodium methyl cocoyl taurate etc.
Use of surfactants in cosmetic preparations is well known for person skilled in the art. Commercially available anti dandruff shampoo compositions also use surfactants as wetting or dispersing agents to deliver the performance benefit of shampoo like cleansing , foam, spreadability etc.
The amount of the total surfactant present in the composition may range from 5% to 35%, preferably from 8% to 20% more preferably from 10% to 15%
Table 1
Examples for Synergy of few surfactants with Azole & Silver compound
S.No Ingredient Log difference in 15 mins Synergy
1 Sodiumlaureth sulphate 0.4 Absent
2 Silver salt @0.025% 0.14 Absent
3 Climbazole @0.5% 0.31 Absent
4 Silversalt @0.025%+climbazole @0.5% 0.082 Absent
5 Sodiumlaureth sulphate+ azole @0.5% 0.4 Absent
6 Sodium laureth sulphate + azole @0.5% + Silver compound @0.025% 4.1 Present
7 Sodium lauroyl sarconsinate 0.2
8 Sodium lauroyl sarcosinate+azole@0.5% 0.3 Absent
9 Sodium lauroyl sarcosinate + azole @0.5% +Silver compound@0.025% 4.1 Present
10 Cocoamidopropylbetaine 0.7
11 Cocoamidopropylbetaine +azole@0.5% 0.9 Absent
12 Cocoamidopropylbetaine + azole @ 0.5% +Silver compound @ 0.025% 4.1 Present
13 Disodiumcocoamphodiacetate 0.2
14 Disodiumcocoamphodiacetate+ azole @0.5% 0.3 Absent
15 Disodiumcocoamphodiacetate + azole @0.5% + Silver compound @0.025% 4.1 Present

The above table 1 illustrates the synergy between the anionic, amphoteric and non-ionic surfactant with Azole & Silver based on the time kill kinetic study and values thus attained.

Table 2
S.No. Ingredients Log difference values
in 15 mins Synergy
1 Guar Hydroxypropyltrimmoniumchloride 0.1
2 Guar Hydroxypropyltrimmoniumchloride + 0.5% azole 0.2 Absent
3 Guar Hydroxypropyltrimmoniumchloride +0.5% azole + 0.025% silver compound 0.0 Absent
4 Dimethiconol emulsion 0.1
5 Dimethiconol emuslion +0.5% azole 0.3 Absent
6 Dimethiconol emulsion +0.5% azole +0.025% silver compound 0.4 Absent
7 EDTA-disodiumsalt 0.3
8 EDTA-disodiumsalt +0.5% azole 0.3 Absent
9 EDTA disodium salt +0.5% azole +0.025% silver compound 0.4 Absent
10 DMDMhydantoin 0.3
11 DMDMhydantoin+0.5% azole 0.0 Absent
12 DMDMhydantoin +0.5% azole +0.025% silver compound 0.0 Absent
13 Fragrance 0.0
14 Fragrance +0.5% azole 0.1 Absent
15 Fragrance +0.5% azole +0.025% silver compound 0.1 Absent
16 Acrylate polymer 0.0
17 Acrylate polymer +0.5% azole 0.2 Absent
18 Acrylate polymer +0.05% azole+0.025% silver compound 0.2 Absent
19 Sodium chloride 0.1
20 Sodium chloride +0.5%azole 0.1 Absent
21 Sodiumchloride+0.5%azole+0.025%silver compound 0.1 Absent
22 Salicylic acid 0.1
23 Salicylic acid +0.5% azole 0.2 Absent
24 Salicylic acid +0.5% azole +0.025% silver compound 0.2 Absent
25 Cocmonoethanolamide 0.1
26 Cocmonoethanolamide+0.5%azole 0.1 Absent
27 Cocmonoethanolamide+0.5%azole+0.025%silver compound 0.1 Absent

The above table 2 illustrates that there is no synergy between the other ingredients used in the composition in the absence of surfactant with Azole & Silver.
Examples of personal care compositions involving a combination of surfactant, azole and silver compound:
Table 3:
Example for shampoo composition
S.No. Name of the ingredient A B C D E
1 Sodium laureth sulphate 13 13 13 13 13
2 EDTA-disodiumsalt 0.05 0.05 0.05 0.05 0.05
3 Salicylic acid 0.5 0.5 0.5 0.5 0.5
4 Azole compound(1) 0.5 - 0.5 0.4 0.5
5 Amino acid based Silver salt (2) - 0.025 0.025 0.0175 0.02
6 Cocomonoethanolamide 1.5 1.5 1.5 1.5 1.5
7 Acrylate polymer(3) 0.2 0.2 0.2 0.2 0.2
8 Guarhydroxypropyltrimmoniumchloride(4) 0.1 0.1 0.1 0.1 0.1
9 DMDM hydantoin 0.25 0.25 0.25 0.25 0.25
10 Silicone emulsion (5) 1 1 1 1 1
11 Fragrance 0.5 0.5 0.5 0.5 0.5
12 Sodium chloride 0.75 0.75 0.75 0.75 0.75
13 DM water q.s.to100 q.s.to100 q.s.to 100 q.s.to 100 q.s.to100
14 Ratio 1:0.05:26 1:0.044:32.5 1:0.04:26

(1) Azole compound used is selected from commonly used azoles benzimidazole, benzothiazole, bifonazole, butaconazole nitrate, climbazole, clotrimazole, ketoconazole, croconazole etc. supplied by Hi-media
(2) Silver salt used is selected fromSilver L-histidine complex, Silver cysteine complexes, Silver (I) complexes of glycine, alanine, valine, leuicine, iso-leuicine, serine, threonine, aspartic acid, proline, phenylalanine, aspartic acid,phenyl alanine, glutamic acid ,tyrosine, aspargine, tryptophan, glutamine, methionine etc
(3) Silicone emulsion included is pre-dispersed emulsion of dimethicone or dimethiconol or trimethysilylamodimethicone or mixtures, which are commercially supplied by DowCorning, Momentive, Wacker etc.

(4) Carbomer used is selected from Carbopol range supplied by Lubrizol
(5) Guar hydroxypropyltrimmonium chloride used is selected from JaguarC13s, supplied by Solvay
Time Kill Kinetic study results
Composition Time Log difference value
A 15 mins 0.27
B 15 mins 0.49
C 15 mins 4.17
D 30 mins 4.2
E 30 mins 4.2

Based on the above log difference data it is established that the azole and silver salt work in synergy and deliver superior antidandruff efficacy in surfactant based personal care compositions like shampoo.
The Anti dandruff efficacy of azole compound is significantly boosted by the presence of silver salt and surfactant wherein the ratio of azole to amino acid based silver salt to surfactant is from 1:0.04: 15 to 1:0.05:50
Method of manufacture:
A process for manufacturing the shampoo composition as described in example A to comprising the steps of
(i) adding at least one or more surfactants selected from anionic, amphoteric/ zwitterionic and non-ionic surfactants or the mixtures thereof along with the required quantity of salicylic acid and azole compound in deionized water followed by heating the mixture to a temperature in the range of 70-90 Deg C and mixing well until a homogenous solution is obtained;

(ii) dispersing the acrylate polymer followed by adding deionized water equal or greater than 10 times the quantity of acrylate polymer and mixing under stirring conditions until the acrylate polymer is dispersed and adding the dispersed acrylate polymer obtained in step(ii) to the composition obtained in step (i);

(iii) dispersing the Guar hydroxypropyltrimoniumchloride followed by adding deionized water equal to or greater than about 10 times the quantity of Guar hydroxypropyltrimoniumchloride and mixing under stirring conditions until the Guar hydroxypropyltrimoniumchloride is dispersed;
(iv) adding the dispersed Guar hydroxypropyltrimoniumchloride solution obtained in step (iii) to the solution obtained in step (ii);
(v) adding Silicone emulsion and amino acid based silver salt to the solution obtained in step (iv) above and mixing the resulting mixture thoroughly until a homogenous solution is obtained.
(vi) optionally, adding other hair benefiting ingredients under stirring conditions with moderate agitation to prevent heavy aeration until the composition is uniform.
Table 4:
Example of shampoo composition
Name of the ingredient F G H C
Sodium laureth sulphate 13 13 13 13
EDTA-disodiumsalt 0.05 0.05 0.05 0.05
Salicylic acid 0.5 0.5 0.5 0.5
Azole compound(1) 0.5 0.5 0.5 0.5
Silver Sulphadiazine 0.025 0 0 0
Silver benzoate 0 0.025 0 0
Silver oxide 0 0 0.025 0
Aminoacid based Silver salt (2) 0 0 0 0.025
Cocmonoethanolamide 1.5 1.5 1.5 1.5
Acrylate polymer(3) 0.2 0.2 0.2 0.2
Guarhydroxypropyltrimmoniumchloride(4) 0.1 0.1 0.1 0.1
DMDMhydantoin 0.25 0.25 0.25 0.25
Dimethiconol emulsion (5) 1 1 1 1
Fragrance 0.5 0.5 0.5 0.5
Sodiumchloride 0.75 0.75 0.75 0.75
DM water q.s.to 100 q.s.to 100 q.s.to
100 q.s.to100
Log difference (15 mins) 1.03 1.59 0.86 4.17

From the examples under table 4 given above it is clear that compositions containing amino acid based silver salt shows higher log difference value as per time kill assay method compared to the compositions containing other silver salts indicating synergy and higher efficacy.
Table 5:
Example of shampoo composition
Name of the ingredient I J K L M N
Sodium laureth sulphate 10 5 15 7.5 20 30
EDTA-disodiumsalt 0.05 0.05 0.05 0.05 0.05 0.05
Salicylic acid 0.5 0.5 0.5 0.5 0.5 0.5
Azole compound (1) 0.5 0.5 0.5 0.5 0.5 0.5
Amino acid based Silver salt (2) 0.025 0.025 0.025 0.02 0.025 0.025
Cocomonoethanolamide 1.5 1.5 1.5 1.5 1.5 1.5
Acrylate polymer(3) 0.2 0.2 0.2 0.2 0.2 0.2
Guarhydroxypropyltrimmoniumchloride(4) 0.1 0.1 0.1 0.1 0.1 0.1
DMDMhydantoin 0.25 0.25 0.25 0.25 0.25 0.25
Dimethiconol emulsion (5) 1 1 1 1 1 1
Fragrance 0.5 0.5 0.5 0.5 0.5 0.5
Sodium chloride 0.75 0.75 0.75 0.75 0.75 0.75
DM water q.s.to 100 q.s.to 100 q.s.TO
100 q.s.to100 q.s.to100 q.s.to100
Log difference (5 mins) 4.10 0.23 4.1 2.08 2.5 0.67
Ratio 1:0.05:20 1:0.05:10 1:0.05:30 1:0.04:15 1:0.05:40 1:0.05:60

Examples above under table 5 clearly illustrates that in Composition J shows when the surfactant concentration is 5% the efficacy is lost which is represented by low log difference value where in the ratio of Azole to silver to Surfactant is 1:0.05:10
Example illustrated in Composition I and K show that when the surfactant concentration is 10% & 15% the efficacy is established which is represented by an acceptable log difference value.
Example illustrated in Composition N show that when the ratio of azole to silver to surfactant is 1:0.05:60 the efficacy is lost which is represented by lower log difference value.
From the above examples it is established that the anti dandruff efficacy of Azole compound is significantly boosted by the presence of silver salt and surfactant wherein the ratio of azole to silver salt to surfactant is from 1:0.04:15 to 1:0.05:50.
It is therefore possible by way of the present advancement to provide for surfactant based anti-dandruff formulation/composition wherein the antidandruff efficacy of an azole compound is synergistically enhanced in the presence of surfactant and silver salt when taken in selective ratios of 1:0.04: 15 to 1:0.05:50. Advantageously, the formulation/ composition of the present invention can be provided in various surfactant based personal care compositions including shampoos, rinse off conditioner compositions and the like to effectively treat dandruff conditions in a subject within a very short application time of less than 30 mins.