US 2016037.4914A2 (19) United States (10) Pub. No.: US 2016/037.4914 A2 (12) Patent Application Publication (43) Pub. Date: Dec. 29, 2016 SHARMA et al. REPUBLICATION (54) ANT-DANDRUFF COMPOSITIONS AND Publication Classification HAR CARE FORMULATIONS CONTAINING (51) Int. Cl. ZINC PYRITHIONE AND QUATERNARY A6IR 8/58 (2006.01) AMMONUMI SALT A6IR 8/4I (2006.01) A6IR 8/49 (2006.01) Applicant: JUBILANT LIFE SCIENCES A61O 5/00 (2006.01) (71) (52) U.S. Cl. LIMITED, NOIDA, UTTAR CPC ................. A61K 8/58 (2013.01); A61O 5/006 PRADESH (IN) (2013.01); A61K 8/416 (2013.01); A61K 8/41 (2013.01); A61K 8/4926 (2013.01); A61 K (72) Inventors: VINEET SHARMA, NOIDA, UTTAR 2800/262 (2013.01); A6 IK 2800/524 PRADESH (IN); ASHUTOSH (2013.01); A6 IK 2800/591 (2013.01) AGARWAL, NOIDA, UTTAR (57) ABSTRACT PRADESH (IN) The present invention discloses a stable biocidal composi tion with enhanced anti-fungal activity at low concentration (21) Appl. No.: 14/916,267 of active(s) and a process for preparing the same. The composition comprises: Zinc pyrithione, C8-C18 quaternary (22) PCT Fed: Sep. 2, 2014 ammonium salt (preferably cetylpyridinium chloride), water miscible glycol/polyol/glycol ether/lactam, organic amine (86) PCT No.: PCT/N2014/000570 and/or alkanol amine The composition can be formulated S 371 (c)(1), into: hair care formulations, antidandruff hair care formula tions, water based paints, coatings, adhesives, hard Surface (2) Date: Mar. 3, 2016 cleaners, fabric care compositions, wood products, plastic Prior Publication Data products and medical products. The biocidal compositions and the resulting formulations are transparent or opaque and (65) US 2016/0220468 A1 Aug. 4, 2016 are stable at varying pH and humidity conditions. US 2016/037.4914 A2 Dec. 29, 2016 ANTI-DANDRUFF COMPOSITIONS AND water system using polyethylenimine has pH of about 9.0 or HAR CARE FORMULATIONS CONTAINING above and reducing pH less than 8.0 leads to precipitation of ZINC PYRITHIONE AND QUATERNARY ZPTO in the system. AMMONUMI SALT 0008 U.S. Pat. No. 4,835,149 discloses the use of alkanol and/or alkyl amines in the Solublizing a metal pyrithione salt CROSS REFERENCE TO RELATED in the preparation of a shampoo effective for the treatment APPLICATIONS of seborrhea and dandruff. The amines include etha nolamine, diethanolamine, monoisopropylamine and others 0001. This application is a National Stage of International together with a cosmetically effective amount of an amin Application No. PCT/IN2014/000570, filed on Sep. 2, 2014, opolycarboxylic acid to regulate the pH of the system which claims priority to Indian patent application no. 2640/ between 6.5-7.5. DEL/2013, filed on Sep. 6, 2013, the disclosures of which 0009 U.S. Pat. No. 6,908,912 discloses a stable, soluble, are incorporated by reference in their entirety. antimicrobial composition where insoluble metal salts of pyrithione in combination with a Zinc source (Zinc salts, FIELD OF INVENTION -Oxides, -hydroxides, -borates, -sulfates, -chlorides etc.) were solubilised in an organic amine (1.2-alkanolamines and 0002 The present invention relates to a stable, transpar 1,3-alkanolamines) alone or in combination with a second ent or opaque biocidal compositions comprising Zinc pyri organic amine (monomeric and polymeric forms of 1.2- thione alone or in combination with a C-C quaternary alkyldiamines and 1,3-alkyldiamines). These compositions ammonium salt, preferably cetylpyridinium chloride. The deliver higher concentration of pyrithione and Zinc ions to compositions possess higher bio-availability and enhanced an application (in-can preservatives and metalworking flu antifungal activity and are capable for being formulated into ids) and thus provide enhanced biocidal efficacy against various personal care and industrial formulations. microorganisms and bio-films. 0010. It is known that below pH 4.5 zinc complex dis BACKGROUND OF THE INVENTION sociates into free pyrithione and above pH 9.5., Zinc complex 0003) Zinc pyrithione (ZPTO), also known as Zinc pyri hydrolyzes to yield ionized pyrithione and Zincate species. dine-2-thiol-N-oxide or bis-(1-hydroxy-2(H) pyridinethion Both free and ionized pyrithione are biologically active but ato-zinc is a broad spectrum antimicrobial agent and has being much more water Soluble than the Zinc complex they been used as fungicide and bactericide in various personal are most susceptible to degradation from exposure to light or care and pharmaceutical products, particularly in anti-dan oxygen. In the patent applications cited above, where dif druff shampoos. ZPTO is also used as a biologically active ferent types of amines have been used to solubilize ZPTO, agent for cutting oils and coolant systems, as an agent for either require pH adjustment, pre-formulation of the actives protecting cellulosic fibres from loss of tensile strength due or give precipitate on pH adjustment. Also these prior arts do to action of fungi and as a preservative for water based not disclose any improved or enhanced antifungal or anti paints, coatings, adhesives, wet-state preservatives, hard microbial activity particularly the anti-dandruff efficacy for Surface cleaners, fabric care compositions, wood products, the resulting solubilized ZPTO as compared to ZPTO sus plastic products, medical products, fibres or any other appli pensions. Further, it is extremely difficult to simultaneously cation where microorganism growth must be stopped or attain Superior hair sensory attributes along with higher slowed. anti-dandruff efficacy from ZPTO containing compositions 0004. The antifungal and antimicrobial activity of ZPTO (US 2006/0182696). depends on the bio-availability of ZPTO molecule on scalp. (0011 WO 20010095717 discloses that cationic polymers Because of poor solubility in water (6-12 ppm), the concen can increase the efficacy of Zinc pyrithione in an anti tration of ZPTO molecules in aqueous media and thereafter dandruff shampoos by enhancing the deposition and reten on hair and scalp also remains low, leading to poor bio tion of the water insoluble ZPTO particles on scalp. Simi availability. Also, when used in personal care formulations, larly polyethylenimine or the reaction product of it produces white Suspension that precipitate in the packag polyethylenimine and ethylene oxide or propylene oxide ing bottle. Therefore, to overcome these disadvantages of (U.S. Pat. No. 3,489,686); water-soluble cationic nitrogen low water solubility, precipitations and poor bio-availability, containing polymers or nitrogen-substituted cellulose ether derivatives (U.S. Pat. No. 3,580,853) and piperidinum chlo ZPTO is generally used in excess (1-2% w/w) but higher ride (U.S. Pat. No. 3,761,417) have also been disclosed to concentration of ZPTO lacks ready consumer acceptability increase the efficacy of ZPTO. However, the effect on due to harshness. adsorption of a metal pyrithione salt such as Zinc pyrithione 0005. There had been many approaches to increase the was not found Sufficient for required or enhanced anti solubilisation and antimicrobial efficacy of zinc pyrithione. dandruff efficacy. 0006 U.S. Pat. No. 3,636,213 discloses solubilisation of (0012 U.S. Pat. No. 4,557,928 describes the use of acry heavy metal pyrithione salts in common organic solvents lamide copolymer quaternium 41 and Methocel to create and/or water by combination with primary alkyl and aryl more efficacious Zinc pyrithione anti-dandruff shampoo but monoamines or polyalkyleneimines, preferably dodecyl these shampoos were found unstable over a long period of amine and diglycol amine for use in hair dressings. The time. compositions have pH's from about 8.5-9.0. 0013 Cationic surfactants such as amino or quaternary 0007 U.S. Pat. No. 3,785,985 and U.S. Pat. No. 3,940, ammonium hydrophilic moieties has been used as cationic 482 describe the solubilization of heavy metal pyrithione Surfactant or emulsifying agent in hair conditioners, sham salts in water and detergent containing compositions with poos, anti-static formulations, fabric softeners and other aliphatic polyamine. However, ZPTO solubilized in alcohol/ cosmetics and toiletries preparations (EP 0034385, EP US 2016/037.4914 A2 Dec. 29, 2016 0941061, US 2008/0057015, U.S. Pat. No. 8,506,942, US DETAILED DESCRIPTION OF THE 2012/0064136, U.S. Pat. No. 8,206,694 and US 2012/ INVENTION 01.00092). Some of them like cetyl pyridinium chloride, is 0022. The present invention provides a stable biocidal also commonly used as antiseptic and/or antimicrobial com composition with enhanced antifungal activity and efficacy. ponent at low concentrations (0.025-0.1%) in many OTC The present invention also provides a biocidal composition health care products (creams, dentifrices, deodorizing and having one or more Cs-Cs quaternary ammonium salt in antiperspirant preparations mouth washes, toothpastes, loz addition to Zinc pyrithione. The biocidal compositions of the enges, throat sprays, cough syrups, nasal sprays and pre present invention possess high bio-availability of Zinc pyri moistened wipes) deodorant. thione. The compositions of the present invention is opaque 0014 US 2007/0020221 describes the use of cetylpyri or transparent. dinium chloride (CPC) as a skin lightening or pigmentation 0023 The inventors of the present invention have sur reducing cosmetic agent in cosmetic compositions to regu prisingly found that quaternary ammonium salt, in particular late the condition of mammalian keratinous tissue particu Cs-Cs quaternary ammonium salt such as cetylpyridinium larly for preventing, retarding, and/or treating uneven skin chloride (CPC) possess significant anti-malassezia or anti tOne. dandruff activity alone and shows enhanced anti-dandruff 0015 US 2006/0241190 describes the specific utility of activity in combination with lower concentrations of ZPTO. cetylpyridinium chloride in cosmetic compositions as a The compositions and formulations of the present invention keratolytic active with SLES for the treatment of psoriasis, possess Superior anti-dandruff efficacy at lower concentra eczema and like skin disorders. tions of active (S), ZPTO and Cs-Cs quaternary ammonium 0016.