Patent Publication Number: US-2009226384-A1

Title: Antimicrobial composition containing triclosan and at least one functionalized hydrocarbon

Description:
FIELD OF INVENTION 
     The present invention relates to a synergistic antimicrobial composition, a process for its preparation and products incorporating the composition. The present invention, particularly, relates to an improved antimicrobial composition comprising an antimicrobial agent, such as, Triclosan (TCS) (Synonyms: 2,4,4′-trichloro-2′-hydroxydiphenyl ether; 5-Chloro-2-(2,4-dichlorophenoxy) phenol; Microban; Irgasan DP 300; Lexol 300; Sterzac; Cloxifenolum; Biofresh) and a functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons and a process for preparing the said composition. By the term functionalized hydrocarbon, it is meant a saturated/unsaturated; linear/branched/cyclic hydrocarbon; having 6-20 carbon atoms; the functional groups present in the hydrocarbon being hydroxyl, carbonyl, carboxyl, amino groups or derivatives thereof. This invention, particularly, relates to compositions which exhibits unexpected and enhanced antimicrobial activity as compared to the inherent antimicrobial activities of the ingredients employed, due to synergy. 
     The composition of the present invention is useful as an antimicrobial composition which includes, but not limited to, hair care, skin care, oral care, hard surface cleaning and similar compositions used to cleanse and/or treat any living or nonliving surface. Accordingly, the synergistic antimicrobial composition of the present invention is applicable to the control of bacterial and fungal growth in cosmetic, personal care (hair care, skin care); home care products (hard surface and other surface treatments), and oral care. Such products include, but not limited to, shampoos, conditioners, hair wash powders, hair and body oils, gels, creams, lotions, cleansers, toners, liquid soaps, soaps, scrubs, microbicidal washes, toothpastes/gels, mouthwashes, deodorants, antiperspirants, surface cleaners and the like. 
     The chlorinated diphenyl ether, Triclosan (TCS), is an antimicrobial agent that has been employed for a variety of purposes for more than 20 years. It is used clinically, in oral hygiene products as well as in a wide range of consumer products. TCS has a broad range of activity that encompasses many, but not all types of Gram positive and Gram negative non-sporulating bacteria, some fungi and viruses. Bacterial spores are unaffected. (Russell A D Wither Triclosan?,  Jour. Antimicrob. Chemo . (2004), 53: 693-695). 
     TCS is relatively non-toxic to humans and other mammals. It is also not found to have any carcinogenic, mutagenic or teratogenic effects. (Bhargava H N &amp; Leonard P A: Triclosan—Applications and Safety.  Am. Jour. Infect. Cont ., (1996), 24 (3): 209-218). 
     However, recently a number of concerns about the overuse of TCS have been raised. These relate particularly to its linkage with ‘allergies’, ‘skin irritation’, ‘development of resistant strains’ and ‘dioxin contamination and destruction of fragile aquatic ecosystems’ (Glaser A: The ubiquitous Triclosan.  Pesticides and You , (2004), 24 (3): 12-17). Therefore there is an urgent need to reduce the quantity of TCS used in products while retaining its antimicrobial efficacy. 
     There remains a very real and substantial need for antimicrobial compounds capable of effectively controlling and/or inhibiting microbial growth in health care, personal care and food industry. Because of stringent environmental regulations, there is a further need to provide biocidal compounds having enhanced antimicrobial effect, which are effective in lower doses than historically used. Use of lower amounts of antimicrobial has a favorable impact on the environment and allows users to realize significant cost savings. 
     Prior Art Knowledge on Synergism Between Antimicrobial and/or Other Ingredients. 
     U.S. Pat. No. 6,689,342 of Pan et al., relates to oral care compounds comprising an effective amount of at least one Tropolone compound in combination with at least one essential oil and a pharmaceutically acceptable oral carrier. They have claimed that the admixture of tropolone compound with antimicrobially active essential oil provides a synergistic antimicrobial effect. 
     U.S. Pat. No. 6,479,456 of Holzner relates to an antimicrobial perfuming composition comprising of perfuming ingredients having an antimicrobial activity of at least 80%, and an active ingredient which may be grapefruit pip, a fumatory extract, a fumaric acid or an ester of fumaric acid/lactic acid. Addition of perfuming composition (in combination with fumaric acid) with TCS/Triclocarbon was found to have synergistic antimicrobial effect. It was found that presence of the active ingredient (fumitory extract or fumaric acid or lactic acid) was critical in the perfuming ingredient to exhibit synergistic activity. Hence the antimicrobial composition comprises of three critical ingredients viz., perfuming agent, fumitory extract and TCS or triclocarbon to exhibit synergistic effect. 
     Jampani et al (WO 0141573) describes antimicrobial compositions comprising at least 30% alcohol (ethyl alcohol/isopropyl alcohol/n-propyl alcohol) and/or an effective amount of TCS in combination with an effective amount of phenoxyethanol, benzalkonium or benzethonium chloride and cocophosphatidyl-dimonium and an effective amount of plant extracts for disinfecting skin. The composition additionally contained an effective amount of essential oils like Australian Tea Tree oil, Lemongrass oil, Thyme oil, Lavender oil, and clove oil in combination. Essential oils were used to increase the emolliency, moisturization and penetration properties of the invention. No synergistic antimicrobial activity between TCS and essential oils used have been disclosed or claimed. Also, this composition is a mixture of several compounds and not a binary combination of an antimicrobial and an essential oil. 
     U.S. Pat. No. 6,515,007 of Murad, relates to a pharmaceutical composition for managing scalp conditions like dandruff, seborrhoeic dermatitis, psoriasis, folliculitis, and thinning hair. The composition includes a therapeutically effective amount of an acidic component having a hydroxy acid or tannic acid or a pharmaceutically acceptable salt thereof; a vitamin A component and an antigrowth agent preferably TCS, clotrimazole and the like, added as a preservative. Together the acidic component, Vitamin A compound and the antigrowth agent may facilitate exfoliation of dead skin, facilitate hydration of scalp and inhibit the presence of microbes and finally assist in scalp management. However no synergy has been claimed. 
     U.S. Pat. No. 6,152,152 of Reynen et al., relates to liquid dishwashing compositions comprising a surfactant, a hydrotope consisting of salts of cumene sulfonate, toluene sulfonate, xylene sulfonate, benzene sulfonate or mixtures thereof; an unsaturated aliphatic terpene alcohol or derivative (e.g. Geraniol, Nerol, Citronellol, Linalool etc.) and a phenolic compound like Eugenol and Thymol. It is a multicomponent synergistic composition. 
     Gaffney et al (U.S. Pat. No. 5,985,934) have presented synergistic admixtures of 2,4,4′-trichloro 2′-hydroxy diphenyl ether and 1,2-dibromo-2,4-dicyanobutane to give synergistic biocidal activities. This patent describes synergistic antimicrobial activities between 2 synthetic compounds. No functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons have been disclosed in this binary mixture. 
     U.S. Pat. No. 6,147,120 of Swart et al., relates to a synergistic composition to treat skin and hair of people and animals, comprising of TCS, chlorhexidine gluconate and an alcohol (ethanol/isopropanol). The compositions were found to provide synergistic antimicrobial effects. They may be used as a single composition or individually in a sequential manner. However, all three components are critical for producing the synergistic effect in the resulting composition. No functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons were used. 
     US Patent 20050019431 of Modak et al., relates to an antimicrobial composition comprising of a quaternium ammonium compound and an essential oil and/or an individual constituent thereof and comprising of 2 or more zinc salts. Synergistic antimicrobial activity was observed with this composition. 
     A review of the literature reveals that binary combination of an antimicrobial agent with functionalized hydrocarbons and/or mixtures containing such functionalized hydrocarbons to enhance the antimicrobial activity of the resulting composition has not been reported so far. Particularly, binary composition of TCS and functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons have not been reported. In contrast to a multicomponent composition, a simple binary composition involving an antimicrobial such as TCS will make the product more economical and environmental friendly; which is the need of the hour. 
     By the term functionalized hydrocarbons, it is meant a saturated/unsaturated; linear/branched/cyclic hydrocarbon; having 6-20 carbon atoms; the functional groups present in the hydrocarbon being hydroxyl, carbonyl, carboxyl, amino groups or derivatives thereof. By way of examples mention is made to monoterpenes or mixtures containing such monoterpenes such as essential oils. 
     The use of the terms ‘synergistic’ and ‘synergistically effective’ used in the present invention means a biological effect created from the application of two or more agents to produce a biological effect that is greater than the sum of the biological effects produced by the application of the individual agents. 
     During the course of developing the present invention we observed that when the ingredients viz. an antimicrobial agent and a functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons are used in combination, synergistic antimicrobial activity was observed. Excellent antimicrobial property was observed when specific amounts of the ingredients and in specific ratio are employed. 
     OBJECTIVES OF THE PRESENT INVENTION 
     Therefore, the main objective of the present invention is to provide a synergistic antimicrobial composition containing an antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     Another objective of the present invention is to provide a synergistic antimicrobial composition containing TCS as the antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     According to yet another objective of the present invention there is provided a synergistic antimicrobial composition containing TCS and the functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons in the ratio in the range of 1:5-1:100. 
     Yet another objective of the present invention is to provide a process for the preparation of a synergistic antimicrobial composition containing an antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     Still another objective of the present invention is to provide a process for the preparation of an synergistic antimicrobial composition containing TCS as the antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     According to another objective of the present invention there is provided products such as but not limited to, shampoo, gel, cream, lotions etc., containing the synergistic composition of the present invention 
     SUMMARY OF THE INVENTION 
     Accordingly, the present invention provides a synergistic antimicrobial composition containing an antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     According to another embodiment of the present invention there is provided a synergistic antimicrobial composition containing TCS as the antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     According to yet another embodiment of the present invention there is provided a synergistic antimicrobial composition containing TCS and the functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons in the ratio in the range of 1:5-1:100. 
     According to yet another embodiment of the present invention there is provided a process for the preparation of a synergistic antimicrobial composition which comprises mixing the antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons. 
     According to yet another embodiment of the present invention there is provided a process for the preparation of a synergistic antimicrobial composition which comprises mixing TCS as the antimicrobial agent and at least one functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons thereof, the ratio of TCS and functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons being in the range of 1:5-1:100. 
     According to another embodiment of the present invention there is provided products such as, but not limited to, shampoo, gel, cream, lotions etc., containing the synergistic composition of the present invention 
     It may be noted that the activity of composition of the present invention is not due to the mere additive property of the ingredients, but due to a surprising synergistic activity. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In a preferred embodiment of the present invention the ratio of TCS:functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons in the composition may be in the range of 1:5-1:100; preferably in the range of 1:10-1:90 and more preferably between 1:20-1:80. 
     In preferred embodiment, the composition of the present invention may be incorporated in products like shampoo, gel, cream, lotions etc., which may comprise a mixture of water, surfactants, thickeners, gelling agents, hydrophobic/hydrophilic polymers, emulsifying agents, emollients or their mixtures, humectants, perfumes, colours, functional ingredients and the like. The compositions of the invention may optionally further include one or more additional antimicrobial agents such as, but not limited to, antibacterial, antiviral, or antifungal agents. Examples of antimicrobial agents include, but not limited to, iodophores, iodine, benzoic acid, dehydroacetic acid, propionic acid, sorbic acid, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben, cetrimide, chlorhexidine (free base and/or salts), other biguanides, chloroerosol, chloroxylenol, benzyl alcohol, bronopol, benzalkonium chloride, benzethonium chloride, ethanol, phenoxyethanol, phenyl ethyl alcohol, 2,4-dicholorobenzyl alcohol, thiomersal, clindamycin, erythromycin, benzoyl peroxide, mupirocin, bacitracin, polymixin B, DMDM Hydantoin (Glydant), GERMALL, Kathon CG, Phenonip, miconazole, fluconazole, itraconazole, etc. 
     The composition of the present invention may contain other ingredients normally employed in such composition, which will aid in the formulation and the use of the composition as a whole. Examples of such ingredients are well known to one skilled in the art. These include substances such as binders, emollients, preservatives, lubricants, colorants, perfumes and the like. Accordingly, when the surface contemplated is scalp/skin/mucous membrane, the composition of the invention may contain ingredients which are physiologically acceptable and which do not contain ingredients which will reverse or retard the action of the synergistic composition. If the surface is a hard non-living surface, suitably accepted ingredients may be present. 
     Products like gels, ointments, lotions, creams, incorporating the composition of the present invention, which may be applied topically to the skin or to the various mucus membranes of the body, including but not limited to those of the oral, nasal, vaginal or rectal cavities. 
     The details of the invention are given in the Examples provided below which are given only to illustrate the invention and therefore should not be construed to limit the scope of the invention. 
     The Examples provided below describe the preparation of the composition which may be incorporated into various products. 
     Example 1 
     Preparation of Composition Containing Triclosan and Lemongrass Oil in a Ratio of 1:20 
     300 mg of TCS was added to 6000 mg of LGO. They were mixed thoroughly, so that the TCS dissolved completely in LGO. The resultant composition was in an oil phase. 
     Example 2 
     Preparation of Composition Containing Triclosan and Lemongrass Oil in a Ratio of 1:80 
     30 mg of TCS was added to 2400 mg of LGO. They were mixed thoroughly, so that the TCS dissolved completely in LGO. The resultant composition was in an oil phase. 
     Example 3 
     Preparation of Composition Containing Triclosan and Citral in a Ratio of 1:20 
     300 mg of TCS was added to 6000 mg of Citral. They were mixed thoroughly, so that the TCS dissolved completely in Citral. The resultant composition was in an oil phase. 
     Example 4 
     Preparation of Composition Containing Triclosan and Citral in a Ratio of 1:80 
     30 mg of TCS was added to 2400 mg of Citral. They were mixed thoroughly, so that the TCS dissolved completely in Citral. The resultant composition was in an oil phase. 
     Example 5 
     Preparation of Composition Containing Triclosan and Nerol in a Ratio of 1:20 
     300 mg of TCS was added to 6000 mg of Nerol. They were mixed thoroughly, so that the TCS dissolved completely in Nerol. The resultant composition was in an oil phase. 
     Example 6 
     Preparation of Composition Containing Triclosan and Nerol in a Ratio of 1:80 
     30 mg of TCS was added to 2400 mg of Nerol. They were mixed thoroughly, so that the TCS dissolved completely in Nerol. The resultant composition was in an oil phase. 
     Example 7 
     Preparation of Composition Containing Triclosan and Geraniol in a Ratio of 1:20 
     300 mg of TCS was added to 6000 mg of Geraniol. They were mixed thoroughly, so that the TCS dissolved completely in Geraniol. The resultant composition was in an oil phase. 
     Example 8 
     Preparation of Composition Containing Triclosan and Geraniol in a Ratio of 1:80 
     30 mg of TCS was added to 2400 mg of Geraniol. They were mixed thoroughly, so that the TCS dissolved completely in Geraniol. The resultant composition was in an oil phase. 
     Illustrative synergistic compositions using other classes of antimicrobial agents such as, Climbazole (CMB), Zinc Pyrithione (ZPTO) and Ketoconazole (KTZ) with functionalized hydrocarbons and/or mixtures containing such functionalized hydrocarbons are described below. 
     Example 9 
     Preparation of Composition Containing Climbazole (CMB) and Lemongrass Oil (LGO) in a Ratio of 1:20 
     300 mg of CMB was added to 6000 mg of LGO. They were mixed thoroughly, so that the CMB dissolved completely in LGO. The resultant composition was in an oil phase. 
     Example 10 
     Preparation of Composition Containing ZPTO and Lemongrass Oil in a Ratio of 1:40 
     125 mg of ZPTO was added to 5000 mg of LGO. They were mixed thoroughly, so that the ZPTO dissolved completely in LGO. The resultant composition was in an oil phase. 
     Example 11 
     Preparation of Composition Containing Ketoconazole (KTZ) and Lemongrass Oil (LGO) in a Ratio of 1:80 
     30 mg of KTZ was added to 2400 mg of LGO. They were mixed thoroughly, so that the KTZ dissolved completely in LGO. The resultant composition was in an oil phase. 
     The following examples described below elucidates the biological efficacy of the individual ingredients of the composition and that of the composition of the present invention. 
     Example 12 
     Estimation of Minimum Inhibitory Concentration (MIC) of Triclosan, Lemongrass Oil, Citral, Nerol, Geraniol, Climbazole, Zinc Pyrithione, &amp; Ketoconazole Individually 
     TCS, LGO, Citral, Nerol, Geraniol, CMB, ZPTO and KTZ were examined for antimicrobial activity individually. The following microbial strains were used: 
     
       
         
           
               
               
               
             
               
                   
                   
               
             
            
               
                   
                 
                   Staphylococcus aureus 
                 
                 MTCC 96 
               
               
                   
                 
                   Staphylococcus epidermidis 
                 
                 MTCC 435 
               
               
                   
                 
                   Bacillus subtilis 
                 
                 MTCC 441 
               
               
                   
                 
                   Candida albicans 
                 
                 MTCC 3017 
               
               
                   
                 
                   Aspergillus niger 
                 
                 MTCC 1344 
               
               
                   
                   Malassezia furfur  ( Pityrosporum ovale ) 
                 MTCC 1374 
               
               
                   
                 
                   Malassezia restricta 
                 
                 CBS 7877 
               
               
                   
                   
               
            
           
         
       
     
     MIC value—is the lowest concentration of the antimicrobial agent required to inhibit growth of the microorganism was determined by the macrobroth double dilution method as per the NCCLS guidelines. (Reference Method for broth dilution antifungal susceptibility testing of Yeasts, Approved Standard; M27A, Vol. 17, No. 9, 1997 &amp; Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved Standard—5 th  Ed., M7-A5, Vol. 20, No. 2, 2000. National Committee for Clinical Laboratory Standards, Wayne, Pa.). 
     Step 1. Preparation of Stock Solution of Test Substance 
     The test substances viz., TCS, CMB, ZPTO, KTZ, LGO, Citral, Nerol &amp; Geraniol were prepared as stock solutions. Weighed 10 mg of TCS, CMB, ZPTO, &amp; KTZ individually and dissolved in 1 ml of solvent (IN NaOH for TCS and DMSO for CMB, ZPTO &amp; KTZ) and diluted in 19 ml SDB. The concentration of the prepared substances was 500 μg/ml. Similarly, weighed 400 mg of LGO, Citral, Nerol &amp; Geraniol individually and dissolved in 2 ml DMSO and diluted in 18 ml SDB. The concentration of LGO, Citral, Nerol &amp; Geraniol was 20000 μg/ml. All test solutions were prepared afresh prior to determination of MIC. 
     Step 2. Preparation of Inoculum 
       S. aureus, S. epidermidis  and  B. subtilis  were cultured in Mueller Hinton Agar (MHA) for 24 hrs. at 37° C. 1-2 colonies were suspended in MHB overnight at 37° C.  C. albicans  and  A. niger  were cultured in Sabauraud Dextrose Agar (SDA) at 28° C. for 24 hrs and 4 days respectively. 1-2 colonies of  C. albicans  was suspended in SDB and cultured overnight at 28° C.  Aspergillus  spores were washed with physiological saline prior to testing.  M. furfur  was cultured in SDA with 1% Tween 80 for 72 hrs at 32° C. Colonies were suspended in SDB with 1% Tween 80 and incubated at 32° C.  M. restricta  was cultured in Dixon agar at 32° C. for 3-4 days. Colonies were suspended in saline prior to testing. 
     Colonies suspended in broth/saline were determined for counts photometrically. (Hammer K A, et al.:  Antimicrob. Agents Chemo ., (2000), 44(2): 467-469). The organisms were diluted such that the final concentration was 1×10 6  cfu/ml for  S. aureus, S. epidermidis  and  B. subtilis,  1×10 5  cfu/ml for  C. albicans  and  A. niger  and 2×10 3  cfu/ml for  M. furfur  and  M. restricta.    
     Step 3. Serial Dilution 
     Double fold serial dilutions were done with the test substance, such that the final concentration of TCS was between 250 μg/ml and 0.03 μg/ml; and that of functionalized hydrocarbon (Citral, Nerol, Geraniol) and/or mixtures containing such functionalized hydrocarbons (LGO) was between 10000 μg/ml-19.53 μg/ml. Inoculated organisms were added to the tubes and required controls were also set up in the assay to rule out contamination/inactivation of the test substance. 
     Step 4. Incubation and Culture: 
     Tubes were incubated for 24 hrs at 37° C. for  S. aureus, S. epidermidis  and  B. subtilis ; at 28° C. for  C. albicans ; for 48 hrs at 28° C. for  A. niger,  32° C. for  M, furfur  and  M. restricta . At the end of the incubation period, 10 μl aliquots from each tube were spot inoculated onto Nutrient agar (for bacteria), SDA (for  C. albicans  &amp;  A. niger ), SDA with 1% Tween 80 for  M. furfur  and Dixon Agar for  M. restricta . The plates were incubated for 24 hrs at 37° C. ( S. aureus, S. epidermidis  &amp;  B. subtilis ), at 28° C. ( C. albicans ); 3-4 days at 28° C. ( A. niger ), 48-72 hrs at 32° C. ( M. furfur  &amp;  M. restricta ) when the colonies became visible. 
     Step 5. Observation: 
     At the end of the incubation period, plates were checked for growth of colonies. The highest dilution which resulted in the inhibition of the growth of the organism was considered as the inhibitory concentration. 
     Table 1 shows the MIC values of the individual ingredients of the composition of the present invention. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 MIC values of individual tested ingredients. 
               
            
           
           
               
               
            
               
                   
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 S. 
                 Test 
                   
                   S. epider - 
                   
                   
                   
                   
                   
               
               
                 No. 
                 Ingredients 
                 
                   S. aureus 
                 
                 
                   midis 
                 
                 
                   B. subtilis 
                 
                 
                   C. albicans 
                 
                 
                   A. niger 
                 
                 
                   M. furfur 
                 
                 
                   M. restricta 
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 TCS 
                 1.95 
                 7.81 
                 15.62 
                 15.62 
                 31.25 
                 62.5 
                 62.5 
               
               
                 2 
                 LGO 
                 1250 
                 625 
                 10000 
                 625 
                 625 
                 39.06 
                 156.25 
               
               
                 3 
                 Citral 
                 312.5 
                 312.5 
                 5000 
                 156.25 
                 625 
                 39.06 
                 156.25 
               
               
                 4 
                 Nerol 
                 5000 
                 1250 
                 10000 
                 1250 
                 1250 
                 156.25 
                 312.5 
               
               
                 5 
                 Geraniol 
                 5000 
                 1250 
                 2500 
                 1250 
                 5000 
                 156.25 
                 312.5 
               
               
                 6 
                 CMB 
                 — 
                 — 
                 — 
                 — 
                 — 
                 1.95 
                 — 
               
               
                 7 
                 ZPTO 
                 — 
                 — 
                 — 
                 — 
                 — 
                 3.9 
                 — 
               
               
                 8 
                 KTZ 
                 — 
                 — 
                 — 
                 — 
                 — 
                 0.48 
                 — 
               
               
                   
               
            
           
         
       
     
     Example 13 
     MIC value of combinations of TCS, CMB, ZPTO &amp; KTZ (antimicrobials) and LGO, Citral, Nerol &amp; Geraniol (Functionalized Hydrocarbon and/or Mixtures Containing Such Functionalized Hydrocarbon) 
     MIC values of the combinations of the composition of the present invention described in Examples 1-11 were determined. 
     Preparation of Stock Solution of Test Substances: 
     a. Preparation for Testing Efficacy of the Composition in the Ratio 1:20 (Composition Described in Examples 1, 3, 5, 7 &amp; 9) 
     140 mg of the sample was dissolved in 2 ml of Dimethyl Sulfoxide (DMSO) and further diluted in 18 ml of SDB. The final concentration of antimicrobial and functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons in the mixture was 333.33 μg/ml and 6666.66 μg/ml respectively. 
     b. Preparation for Testing Efficacy of the Composition in the Ratio 1:40 (Composition Described in Examples 10) 
     205 mg of the sample was dissolved in 2 ml of Dimethyl Sulfoxide (DMSO) and further diluted in 18 ml of SDB. The final concentration of antimicrobial and functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons in the mixture was 250 μg/ml and 10000 μg/ml respectively. 
     c. Preparation for Testing Efficacy of the Composition in the Ratio 1:80 (Composition Described in Examples 2, 4, 6, 8, &amp; 11) 
     270 mg of the sample was dissolved in 2 ml of Dimethyl Sulfoxide (DMSO) and further diluted in 18 ml of SDB. The final concentration of antimicrobial and functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons in the mixture was 166.66 μg/ml and 13333.33 μg/ml respectively. 
     These combinations were serially diluted and MIC determined against microorganisms as explained in Example 12. Tables 2-5 show that the concentration of the components of the combination where growth inhibition of the organism was achieved. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Inhibitory concentration of the components of the 
               
               
                 combinations (TCS &amp; LGO) in different ratios. 
               
            
           
           
               
               
            
               
                   
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Example 1 
                 Example 2 
               
               
                 S. 
                   
                 TCS + LGO (1:20) 
                 TCS + LGO (1:80) 
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 Organism 
                 TCS 
                 LGO 
                 TCS 
                 LGO 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 
                   S. aureus 
                 
                 1.3 
                 26.04 
                 0.65 
                 13.02 
               
               
                 2 
                 
                   S. epidermidis 
                 
                 1.3 
                 26.04 
                 2.6 
                 208.33 
               
               
                 3 
                 
                   B. subtilis 
                 
                 0.65 
                 13.02 
                 1.3 
                 104.16 
               
               
                 4 
                 
                   C. albicans 
                 
                 5.2 
                 104.16 
                 1.3 
                 104.16 
               
               
                 5 
                 
                   A. niger 
                 
                 10.41 
                 208.33 
                 2.6 
                 208.33 
               
               
                 6 
                 
                   M. furfur 
                 
                 1.3 
                 26.04 
                 0.65 
                 13.02 
               
               
                 7 
                 
                   M. restricta 
                 
                 2.6 
                 52.08 
                 0.65 
                 13.02 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 2, combinations of TCS with LGO in different ratios surprisingly exhibit pronounced lowering of MIC values of individual components compared to that of the parent compound over a wide compositional ranges and against a wide ranges of organisms. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Inhibitory concentration of the components of the 
               
               
                 combinations (TCS &amp; Citral) in different ratios 
               
            
           
           
               
               
            
               
                   
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Example 3 
                 Example 4 
               
               
                 S. 
                   
                 TCS + Citral (1:20) 
                 TCS + Citral (1:80) 
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 Organism 
                 TCS 
                 Citral 
                 TCS 
                 Citral 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 
                   S. aureus 
                 
                 0.16 
                 3.25 
                 0.65 
                 13.02 
               
               
                 2 
                 
                   S. epidermidis 
                 
                 2.6 
                 52.08 
                 2.6 
                 208.33 
               
               
                 3 
                 
                   B. subtilis 
                 
                 5.2 
                 104.16 
                 2.6 
                 208.33 
               
               
                 4 
                 
                   C. albicans 
                 
                 2.6 
                 52.08 
                 0.65 
                 13.02 
               
               
                 5 
                 
                   A. niger 
                 
                 10.41 
                 208.33 
                 5.2 
                 416.66 
               
               
                 6 
                 
                   M. furfur 
                 
                 1.3 
                 26.04 
                 0.65 
                 13.02 
               
               
                 7 
                 
                   M. restricta 
                 
                 2.6 
                 52.08 
                 0.65 
                 13.02 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 3, combinations of TCS with Citral in different ratios surprisingly exhibits pronounced lowering of MIC values of individual components compared to that of the parent compound over a wide compositional range and against a wide range of organisms 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Inhibitory concentration of the components of the 
               
               
                 combinations (TCS &amp; Nerol) in different ratios 
               
            
           
           
               
               
            
               
                   
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Example 5 
                 Example 6 
               
               
                 S. 
                   
                 TCS + Nerol (1:20) 
                 TCS + Nerol (1:80) 
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 Organism 
                 TCS 
                 Nerol 
                 TCS 
                 Nerol 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 
                   S. aureus 
                 
                 0.16 
                 3.25 
                 0.32 
                 26.04 
               
               
                 2 
                 
                   S. epidermidis 
                 
                 1.3 
                 26.04 
                 2.6 
                 208.33 
               
               
                 3 
                 
                   B. subtilis 
                 
                 2.6 
                 52.08 
                 2.6 
                 208.33 
               
               
                 4 
                 
                   C. albicans 
                 
                 10.41 
                 208.33 
                 2.6 
                 208.33 
               
               
                 5 
                 
                   A. niger 
                 
                 10.41 
                 208.33 
                 2.6 
                 208.33 
               
               
                 6 
                 
                   M. furfur 
                 
                 1.3 
                 26.04 
                 0.65 
                 13.02 
               
               
                 7 
                 
                   M. restricta 
                 
                 5.2 
                 104.16 
                 1.3 
                 104.16 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 4, combinations of TCS with Nerol in different ratios surprisingly exhibit pronounced lowering of MIC values of individual components compared to that of the parent compound over a wide compositional ranges and against wide ranges of organisms 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Inhibitory concentration of the components of the 
               
               
                 combinations (TCS &amp; Geraniol) in different ratios 
               
            
           
           
               
               
            
               
                   
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Example 7 
                 Example 8 
               
               
                 S. 
                   
                 TCS + Geraniol (1:20) 
                 TCS + Geraniol (1:80) 
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 Organism 
                 TCS 
                 Geraniol 
                 TCS 
                 Geraniol 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 
                   S. aureus 
                 
                 0.32 
                 6.51 
                 0.65 
                 13.02 
               
               
                 2 
                 
                   S. epidermidis 
                 
                 1.3 
                 26.04 
                 1.3 
                 104.16 
               
               
                 3 
                 
                   B. subtilis 
                 
                 2.6 
                 52.08 
                 2.6 
                 208.33 
               
               
                 4 
                 
                   C. albicans 
                 
                 10.41 
                 208.33 
                 2.6 
                 208.33 
               
               
                 5 
                 
                   A. niger 
                 
                 5.2 
                 104.16 
                 2.6 
                 208.33 
               
               
                 6 
                 
                   M. furfur 
                 
                 1.3 
                 26.04 
                 0.65 
                 13.02 
               
               
                 7 
                 
                   M. restricta 
                 
                 5.2 
                 104.16 
                 1.3 
                 104.16 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 5, combinations of TCS with Geraniol in different ratios surprisingly exhibit pronounced lowering of MIC values of individual components compared to that of the parent compound over wide compositional ranges and against wide ranges of organisms. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Inhibitory concentration of the components of the combinations 
               
               
                 (CMB, ZPTO, KTZ &amp; LGO) in different ratios 
               
            
           
           
               
               
            
               
                   
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 Example 9 
                 Example 10 
                 Example 11 
               
               
                   
                   
                 CMB + LGO 
                 ZPTO + LGO 
                 KTZ + LGO 
               
               
                 S. 
                   
                 (1:20) 
                 (1:40) 
                 (1:80) 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 No. 
                 Organism 
                 CMB 
                 LGO 
                 ZPTO 
                 LGO 
                 KTZ 
                 LGO 
               
               
                   
               
               
                 1 
                 
                   M. furfur 
                 
                 0.32 
                 6.51 
                 0.24 
                 9.76 
                 0.08 
                 6.51 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 6, combinations of CMB, ZPTO, KTZ with LGO in different ratios surprisingly exhibit pronounced lowering of MIC values of individual components compared to that of the parent compound over wide compositional ranges and against wide ranges of organisms. 
     The above Examples demonstrate that combinations of TCS, CMB, ZPTO, KTZ (antimicrobials) with LGO, Citral, Nerol, Geraniol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) in different ratios surprisingly exhibit pronounced lowering of MIC values than the parent compound over a wide compositional ranges and against wide ranges of organisms. 
     Fractional Inhibitory Concentration (FIC) Index was calculated from the Minimal Bactericidal/Fungicidal Concentration (MBC/MFC) by using the following equation: 
     
       
         
           
             
               FIC 
                
               
                   
               
                
               Index 
             
             = 
             
               
                 
                   
                     
                       
                         MBC 
                          
                         
                             
                         
                          
                         of 
                          
                         
                             
                         
                          
                         drug 
                          
                         
                             
                         
                          
                         A 
                          
                         
                             
                         
                          
                         when 
                       
                     
                   
                   
                     
                       
                         used 
                          
                         
                             
                         
                          
                         in 
                          
                         
                             
                         
                          
                         combination 
                       
                     
                   
                 
                 
                   MBC 
                    
                   
                       
                   
                    
                   of 
                    
                   
                       
                   
                    
                   Drug 
                    
                   
                       
                   
                    
                   A 
                 
               
               + 
               
                 
                   
                     
                       
                         MBC 
                          
                         
                           
                               
                           
                            
                           
                               
                           
                         
                          
                         of 
                          
                         
                             
                         
                          
                         drug 
                          
                         
                             
                         
                          
                         B 
                          
                         
                             
                         
                          
                         when 
                       
                     
                   
                   
                     
                       
                         used 
                          
                         
                             
                         
                          
                         in 
                          
                         
                             
                         
                          
                         combination 
                       
                     
                   
                 
                 
                   MBC 
                    
                   
                       
                   
                    
                   of 
                    
                   
                       
                   
                    
                   Drug 
                    
                   
                       
                   
                    
                   B 
                 
               
             
           
         
       
     
     An FIC Index of &lt;0.5 was considered as synergistic effect; 0.5-1.0 was considered as additive effect, and &gt;1.0 was considered as antagonistic effect. 
     Table 7 shows FIC Index of antimicrobials in combinations with functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons against various microorganisms studied. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 FIC Index of combinations 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   S. epider - 
                   
                   
                   
                   
                   
               
               
                 Sample 
                 
                   S. aureus 
                 
                 
                   midis 
                 
                 
                   B. subtilis 
                 
                 
                   C. albicans 
                 
                 
                   Asp. niger 
                 
                 
                   M. furfur 
                 
                 
                   M. restricta 
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Example 1 
                 0.676 
                 0.207 
                 0.042 
                 0.499 
                 0.666 
                 0.686 
                 0.374 
               
               
                 TCS + LGO 
               
               
                 (1:20) 
               
               
                 Example 2 
                 0.374 
                 0.665 
                 0.093 
                 0.249 
                 0.416 
                 0.343 
                 0.343 
               
               
                 TCS + LGO 
               
               
                 (1:80) 
               
               
                 Example 3 
                 0.092 
                 0.498 
                 0.352 
                 0.499 
                 0.666 
                 0.686 
                 0.374 
               
               
                 TCS + Citral 
               
               
                 (1:20) 
               
               
                 Example 4 
                 0.374 
                 0.998 
                 0.207 
                 0.124 
                 0.832 
                 0.343 
                 0.343 
               
               
                 TCS + Citral 
               
               
                 (1:80) 
               
               
                 Example 5 
                 0.082 
                 0.186 
                 0.171 
                 0.833 
                 0.499 
                 0.186 
                 0.416 
               
               
                 TCS + Nerol 
               
               
                 (1:20) 
               
               
                 Example 6 
                 0.169 
                 0.498 
                 0.186 
                 0.332 
                 0.249 
                 0.093 
                 0.353 
               
               
                 TCS + Nerol 
               
               
                 (1:80) 
               
               
                 Example 7 
                 0.165 
                 0.186 
                 0.186 
                 0.833 
                 0.186 
                 0.186 
                 0.416 
               
               
                 TCS + Geraniol 
               
               
                 (1:20) 
               
               
                 Example 8 
                 0.335 
                 0.249 
                 0.249 
                 0.332 
                 0.124 
                 0.093 
                 0.353 
               
               
                 TCS + Geraniol 
               
               
                 (1:80) 
               
               
                 Example 9 
                 — 
                 — 
                 — 
                 — 
                 — 
                 0.33 
                 — 
               
               
                 CMB + LGO 
               
               
                 (1:20) 
               
               
                 Example 10 
                 — 
                 — 
                 — 
                 — 
                 — 
                 0.31 
                 — 
               
               
                 ZPTO + LGO 
               
               
                 (1:40) 
               
               
                 Example 11 
                 — 
                 — 
                 — 
                 — 
                 — 
                 0.332 
                 — 
               
               
                 KTZ + LGO 
               
               
                 (1:80) 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 7, FIC Index shows synergistic activity for combinations of TCS CMB, ZPTO, KTZ (antimicrobials) with LGO, Citral, Nerol, Geraniol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) over wide compositional ranges. 
     The enhancement levels of compound A in the presence of another B was calculated as follows: 
     
       
         
           
             
               
                 
                   
                     Enhancement 
                      
                     
                         
                     
                      
                     factor 
                      
                     
                         
                     
                      
                     of 
                   
                 
               
               
                 
                   
                     
                       
                         
                           compound 
                            
                           
                               
                           
                            
                           A 
                            
                           
                               
                           
                            
                           in 
                            
                           
                               
                           
                            
                           presence 
                         
                       
                     
                     
                       
                         
                           of 
                            
                           
                               
                           
                            
                           Compound 
                            
                           
                               
                           
                            
                           B 
                         
                       
                     
                   
                 
               
             
             = 
             
               
                 MBC 
                  
                 
                     
                 
                  
                 of 
                  
                 
                     
                 
                  
                 compound 
                  
                 
                     
                 
                  
                 A 
                  
                 
                     
                 
                  
                 alone 
               
               
                 
                   
                     
                       MBC 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       compound 
                        
                       
                           
                       
                        
                       A 
                     
                   
                 
                 
                   
                     
                       in 
                        
                       
                           
                       
                        
                       presence 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       B 
                     
                   
                 
               
             
           
         
       
     
     Table 8 shows enhancement factor of antimicrobials (TCS, CMB, ZPTO &amp; KTZ) in presence of LGO, Citral, Nerol &amp; Geraniol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) in various ratios against various microorganisms: 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Enhancement factor of Antimicrobials 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   S. epider - 
                   
                   
                   
                   
                   
               
               
                 Sample 
                 
                   S. aureus 
                 
                 
                   midis 
                 
                 
                   B. subtilis 
                 
                 
                   C. albicans 
                 
                 
                   A. niger 
                 
                 
                   M. furfur 
                 
                 
                   M. restricta 
                 
               
               
                   
               
               
                 Example 1 
                 1.5×   
                 6× 
                 24×  
                 3× 
                 3× 
                 48× 
                 24× 
               
               
                 TCS + LGO 
               
               
                 (1:20) 
               
               
                 Example 2 
                 3× 
                 3× 
                 12×  
                 12×  
                 12×  
                 96× 
                 96× 
               
               
                 TCS + LGO 
               
               
                 (1:80) 
               
               
                 Example 3 
                 12×  
                 3× 
                 3× 
                 6× 
                 3× 
                 48× 
                 24× 
               
               
                 TCS + Citral 
               
               
                 (1:20) 
               
               
                 Example 4 
                 3× 
                 3× 
                 6× 
                 24×  
                 6× 
                 96× 
                 96× 
               
               
                 TCS + Citral 
               
               
                 (1:80) 
               
               
                 Example 5 
                 12×  
                 6× 
                 6× 
                 1.5×   
                 3× 
                 48× 
                 25× 
               
               
                 TCS + Nerol 
               
               
                 (1:20) 
               
               
                 Example 6 
                 6× 
                 3× 
                 6× 
                 6× 
                 12×  
                 96× 
                 48× 
               
               
                 TCS + Nerol 
               
               
                 (1:80) 
               
               
                 Example 7 
                 6× 
                 6× 
                 6× 
                 1.5×   
                 6× 
                 48× 
                 25× 
               
               
                 TCS + Geraniol 
               
               
                 (1:20) 
               
               
                 Example 8 
                 3× 
                 6× 
                 6× 
                 6× 
                 12×  
                 96× 
                 48× 
               
               
                 TCS + Geraniol 
               
               
                 (1:80) 
               
               
                 Example 9 
                 — 
                 — 
                 — 
                 — 
                 — 
                  6× 
                 — 
               
               
                 CMB + LGO 
               
               
                 (1:20) 
               
               
                 Example 10 
                 — 
                 — 
                 — 
                 — 
                 — 
                 16× 
                 — 
               
               
                 ZPTO + LGO 
               
               
                 (1:40) 
               
               
                 Example 11 
                 — 
                 — 
                 — 
                 — 
                 — 
                  6× 
                 — 
               
               
                 KTZ + LGO 
               
               
                 (1:80) 
               
               
                   
               
            
           
         
       
     
     As seen from the Table 8, in the presence of LGO, Citral, Nerol &amp; Geraniol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons), activity of TCS, CMB, ZPTO &amp; KTZ (antimicrobials) is enhanced several folds. A phenomenal increase is seen especially against  M. furfur  and  M. restricta.    
     Combinations of Triclosan and LGO, Citral, Nerol &amp; Geraniol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) apart from giving an overall enhanced antimicrobial activity, was surprisingly showing significant anti-dandruff activity too. 
     Example 14 
     Estimation of MIC Values Against  M. furfur  with Shampoo Incorporated with Synergistic Compositions of the Present Invention 
     Synergistic compositions were of Triclosan and LGO &amp; Nerol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) as described in Examples 1 &amp; 2, as well as Examples 5 &amp; 6, were prepared and incorporated in the shampoo base (Shampoo composition: SLES—36%, Palmkernalamide MEA—1%, Ethyleneglycol distearate—0.5%, Cocamidopropyl Betaine—6%, Lamesoft PO 65—1.5%, DC1870—5%, Salcare Super 7—0.75%, Jaguar Excel—0.1%, PEG 7 Glyceryl cocoate—1.5%, Disodium Ethylenediaminetetraacetic acid (EDTA)—0.05%, Triethanolamine TEA—0.3%, Color—0.0006%, Perfume 0.7%, Water—q.s). The MIC Values of the resultant shampoos were estimated via adaptation of the procedure described in Example 12. Table 9 &amp; 10 shows the MIC values of shampoos incorporated with synergistic composition of the present invention and individual ingredients of the composition of the present invention. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 MIC values of shampoos incorporated with synergistic compositions 
               
               
                 of the present invention against  M. furfur . 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 MIC (μg/ml) 
               
               
                 S. 
                   
                   
                   
                 of test 
               
               
                 No 
                 Composition (w/w in shampoo) 
                 Example # 
                 Ratio 
                 shampoo 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 Shampoo Base (Control) 
                   
                 — 
                 10000 
               
               
                 2 
                 Base + 0.3% TCS + 6% LGO 
                 Example 1 
                 1:20 
                 78.12 
               
               
                 3 
                 Base + 0.03% TCS + 2.4% LGO 
                 Example 2 
                 1:80 
                 78.12 
               
               
                 4 
                 Base + 0.3% TCS + 6% Nerol 
                 Example 5 
                 1:20 
                 78.12 
               
               
                 5 
                 Base + 0.03% TCS + 2.4% Nerol 
                 Example 6 
                 1:80 
                 156.25 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 MIC values of shampoos incorporated with individual ingredients 
               
               
                 of the compositions of the present invention against  M. furfur . 
               
            
           
           
               
               
               
            
               
                   
                 Composition 
                 MIC (μg/ml) of 
               
               
                 S. No 
                 (w/w in shampoo) 
                 test shampoo 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 Base + 0.3% TCS 
                 1250 
               
               
                 2 
                 Base + 0.03% TCS 
                 10000 
               
               
                 3 
                 Base + 6% LGO 
                 625 
               
               
                 4 
                 Base + 2.4% LGO 
                 2500 
               
               
                 5 
                 Base + 6% Nerol 
                 1250 
               
               
                 6 
                 Base + 2.4% Nerol 
                 2500 
               
               
                   
               
            
           
         
       
     
     From Example 14 (Tables 9 &amp; 10), it is evident that when these synergistic composition of the present invention are incorporated into products viz. shampoo, the synergistic effect is exhibited by significant lowering of the MIC value (Table 9) when compared with individual components being incorporated in the product base (Table 10). This indeed demonstrates the usefulness of such compositions as practical propositions for antimicrobial activities. 
     Example 15 
     Estimation of MIC Values of Hair Oil Incorporating Synergistic Compositions Against  M. furfur    
     Synergistic compositions of TCS with LGO &amp; Nerol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) as described in Examples 1 &amp; 2, as well as Examples 5 &amp; 6, were used and incorporated in a conventional hair oil base (Composition: Gingelly oil—25%, Coconut oil—25%, Mineral oil—49.8%, BHT 0.2%). The MIC values of the resultant oils were estimated via adaptation of the procedure described in Example 12. Table 11 &amp; 12 shows the MIC values of hair oils incorporated with synergistic composition of the present invention and individual ingredients of the composition of the present invention. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 MIC values of Hair oil incorporated with synergistic 
               
               
                 compositions against  M. furfur . 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 MIC (μg/ml) 
               
               
                 S. 
                   
                   
                   
                 of test 
               
               
                 No 
                 Composition (w/w in hair oil) 
                 Example # 
                 Ratio 
                 hair oil 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 Hair oil Base (Control) 
                   
                 — 
                 2500 
               
               
                 2 
                 Base + 0.3% TCS + 6% LGO 
                 Example 1 
                 1:20 
                 19.53 
               
               
                 3 
                 Base + 0.03% TCS + 2.4% LGO 
                 Example 2 
                 1:80 
                 39.06 
               
               
                 4 
                 Base + 0.3% TCS + 6% Nerol 
                 Example 5 
                 1:20 
                 39.06 
               
               
                 5 
                 Base + 0.03% TCS + 2.4% Nerol 
                 Example 6 
                 1:80 
                 19.53 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 MIC values of Hair oil incorporated with incorporated with individual 
               
               
                 ingredients of the compositions against  M. furfur . 
               
            
           
           
               
               
               
            
               
                   
                 Composition 
                 MIC (μg/ml) of 
               
               
                 S. No 
                 (w/w in hair oil) 
                 test hair oil 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 Base + 0.3% TCS 
                 78.12 
               
               
                 2 
                 Base + 0.03% TCS 
                 312.5 
               
               
                 3 
                 Base + 6% LGO 
                 156.25 
               
               
                 4 
                 Base + 2.4% LGO 
                 625 
               
               
                 5 
                 Base + 6% Nerol 
                 156.25 
               
               
                 6 
                 Base + 2.4% Nerol 
                 1250 
               
               
                   
               
            
           
         
       
     
     From the Example 15 (Tables 11 &amp; 12), it is evident that when these synergistic composition of the present invention are incorporated into products, the synergistic effect is exhibited by significant lowering of the MIC (Table 11) value when compared with individual components being incorporated in product base (Table 12). This indeed demonstrates the usefulness of such compositions as practical propositions for antimicrobial activities. 
     Example 16 
     Estimation of MIC Values of Hair Gel Incorporating Synergistic Compositions Against  M. furfur    
     Synergistic compositions were of TCS with LGO &amp; Nerol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) as described in Examples 1 &amp; 2, as well as Examples 5 &amp; 6, were used and incorporated in a conventional hair gel base (Composition: Carbopol—0.5%, PVP/VA Polymer—2.45%, Glycerin—1.5%, Panthenal—0.2%, Glydant—0.3%, Aloe vera extract—0.1%, Kerasal—0.05%, Calcunent—0.001%, TEA—0.70%, Water—q.s). The MIC values of the resultant gels were estimated via adaptation of the procedure described in Example 12. Table 13 &amp; 14 shows the MIC values of hair gels incorporated with synergistic composition of the present invention and individual ingredients of the composition of the present invention. 
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 MIC values of Hair gel incorporated with synergistic 
               
               
                 compositions against  M. furfur . 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 MIC (μg/ml) 
               
               
                 S. 
                   
                   
                   
                 of test 
               
               
                 No 
                 Composition (w/w in hair gel) 
                 Example 
                 Ratio 
                 hair gel 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 Hair gel Base (Control) 
                   
                 — 
                 10000 
               
               
                 2 
                 Base + 0.3% TCS + 6% LGO 
                 Example 1 
                 1:20 
                 156.25 
               
               
                 3 
                 Base + 0.03% TCS + 2.4% LGO 
                 Example 2 
                 1:80 
                 312.5 
               
               
                 4 
                 Base + 0.3% TCS + 6% Nerol 
                 Example 5 
                 1:20 
                 312.5 
               
               
                 5 
                 Base + 0.03% TCS + 2.4% Nerol 
                 Example 6 
                 1:80 
                 625 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 MIC values of Hair gel incorporated with individual 
               
               
                 ingredients of the compositions against  M. furfur . 
               
            
           
           
               
               
               
            
               
                   
                 Composition 
                 MIC (μg/ml) 
               
               
                 S. No 
                 (w/w in hair gel) 
                 of test hair gel 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                 Base + 0.3% TCS 
                 2500 
               
               
                 2 
                 Base + 0.03% TCS 
                 10000 
               
               
                 3 
                 Base + 6% LGO 
                 625 
               
               
                 4 
                 Base + 2.4% LGO 
                 2500 
               
               
                 5 
                 Base + 6% Nerol 
                 2500 
               
               
                 6 
                 Base + 2.4% Nerol 
                 10000 
               
               
                   
               
            
           
         
       
     
     From the Example 16 (Tables 13 &amp; 14), it is evident that when these synergistic composition of the present invention are incorporated into products, the synergistic effect is exhibited by significant lowering of the MIC value (Table 13) when compared with individual components being incorporated in product base (Table 14). This indeed demonstrates the usefulness of such compositions as practical propositions for antimicrobial activities. 
     Example 17 
     Estimation of MIC Values of Skin Lotion Incorporating Synergistic Compositions Against  S. aureus  and  C. albicans    
     Synergistic compositions were of TCS with LGO &amp; Nerol (functionalized hydrocarbon and/or mixtures containing such functionalized hydrocarbons) as described in Examples 1 &amp; 2, as well as Examples 5 &amp; 6, were used and incorporated in a conventional skin lotion base (Composition: LLP—10%, WPJ—1%, CCTG—2%, Cetyl alcohol—0.5%, Myrj 59—2%, GMS-Se—1%, Cetyl palmitate—1%, Dimethicone—2%, Stearic acid—3%, Olive oil—0.2%, EDTA—0.05%, Glycerin—5%, KOH—0.2%, D.M. Water—q.s to 100%.). The MIC values of the resultant skin lotions were estimated via adaptation of the procedure described in Example 12. Table 15 &amp; 16 shows the MIC values of hair gels incorporated with synergistic composition of the present invention and individual ingredients of the composition of the present invention. 
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 MIC values of skin lotion incorporated with synergistic compositions 
               
               
                 against  S. aureus  and  C. albicans . 
               
            
           
           
               
               
               
            
               
                 S. 
                 Composition 
                 MIC (μg/ml) 
               
            
           
           
               
               
               
               
               
               
            
               
                 No 
                 (w/w in skin lotion) 
                 Example # 
                 Ratio 
                 
                   S. aureus 
                 
                 
                   C. albicans 
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 Skin lotion Base (Control) 
                   
                 — 
                 &gt;20000 
                 &gt;20000 
               
               
                 2 
                 Base + 0.3% TCS + 6% LGO 
                 Example 1 
                 1:20 
                 1250 
                 312.5 
               
               
                 3 
                 Base + 0.03% TCS + 2.4% LGO 
                 Example 2 
                 1:80 
                 2500 
                 625 
               
               
                 4 
                 Base + 0.3% TCS + 6% Nerol 
                 Example 5 
                 1:20 
                 2500 
                 312.5 
               
               
                 5 
                 Base + 0.03% TCS + 2.4% Nerol 
                 Example 6 
                 1:80 
                 2500 
                 625 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 MIC values of skin lotion incorporated with individual ingredients 
               
               
                 of the compositions against  S. aureas  and  C. albicans . 
               
            
           
           
               
               
               
               
            
               
                   
                 Composition 
                 MIC (μg/ml) 
                   
               
            
           
           
               
               
               
               
            
               
                 S. No 
                 (w/w in skin lotion) 
                 
                   S. aureus 
                 
                 
                   C. albicans 
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1 
                 Base + 0.3% TCS 
                 5000 
                 5000 
               
               
                 2 
                 Base + 0.03% TCS 
                 &gt;20000 
                 &gt;20000 
               
               
                 3 
                 Base + 6% LGO 
                 5000 
                 2500 
               
               
                 4 
                 Base + 2.4% LGO 
                 20000 
                 10000 
               
               
                 5 
                 Base + 6% Nerol 
                 10000 
                 5000 
               
               
                 6 
                 Base + 2.4% Nerol 
                 20000 
                 10000 
               
               
                   
               
            
           
         
       
     
     From the Example 17 (Tables 15 &amp; 16), it is evident that when these synergistic composition of the present invention are incorporated into products, the synergistic effect is exhibited by significant lowering of the MIC value (Table 15) when compared with individual components being incorporated in product base (Table 16). This indeed demonstrates the usefulness of such compositions as practical propositions for antimicrobial activities. 
     ADVANTAGES OF THE PRESENT INVENTION 
     1. The composition provides antimicrobial properties at concentrations much below the levels at which similar properties are delivered by the single ingredient alone thereby making it more efficacious (See Tables 1-6). 
     2. The composition facilitates better inhibition of wider range of microorganisms as compared to the individual component of the composition (See Tables 1-5). 
     3. The synergistic compositions are applicable to the control of bacterial and fungal growth in cosmetic/personal care (hair care, skin care) and home care (hard surface, other surface cleaning), which otherwise with only the individual component may not have been effective. Such products include, but are not limited to shampoos, conditioners, hair wash powders, hair oils, gels, creams, lotions, cleaners, liquid soaps, soaps, scrubs, microbicidal washes, tooth pastes/gels, mouthwashes/rinses, deodorants, antiperspirants, surface cleaners, and the like. 
     4. The synergistic composition reduces the amount of antimicrobial agent which not only reduces the cost but also provides use of lower concentration of the agent thereby reducing the exposure of the agent and consequently the side effects if any on the user. 
     5. Use of lower concentration of the antimicrobial agent also renders it more environment friendly.