Abstract:
An antimicrobial composition of 3-iodo-2-propynylbutyl carbamate (IPBC) and 1,3-butylene glycol (BG) as solvent, in a defined weight ratio, preferably 9-11% IPBC and 89-91% BG, and personal care formulations including the composition in an amount of about 0.1-0.2% therein, at a pH of 4-9, is described.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to preservative compositions for inhibiting the growth of microorganisms and fungi in personal care and industrial applications, and, more particularly, to preservative compositions which are effective and safe, are formaldehyde-free and paraben-free, are temperature and pH stable, and have broad compatibility with raw materials present therein. 
     2. Description of the Prior Art 
     Preservative compositions having antibacterial properties suitable for use in personal care and industrial applications have been described in the literature, see U.S. Pat. Nos. 3,923,870; 4,844,891; 5,428,050; 5,496,842; 5,552,425; 5,631,273; 6,582,627; and Published Application No. 2003/0039580. 
     However, each personal care formulation requires a preservative system that meets its specific needs, particularly for effective and safe preservation as determined by challenge testing. 
     SUMMARY OF THE INVENTION 
     What is described herein is an antimicrobial composition consisting essentially of 3-iodo-2-propynylbutyl carbamate (IPBC) in 1,3-butylene glycol (BG) as solvent, preferably, by wt., 9-11% IPBC in 89-91% BG, and personal care formulations containing 0.1-0.2% by wt. of the preservative composition, at a pH of 4-9 of the composition. 
     The preservative compositions herein are effective and safe, are formaldehyde-free and paraben-free, are temperature and pH stable, and are compatible with raw materials present in both personal care and industrial products. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The invention will now be illustrated in more detail by the following examples. 
     EXAMPLE 1 
                                                                 NON-IONIC MOISTURIZER                        SUP-       PHASE   INGREDIENT   % W/W   PLIER                    A   Deionized Water   78.70               Disodium EDTA (Versene NA)   0.10   Dow           Glycerin (and) Glyceryl Acrylate/   0.50   ISP           Acrylic Acid Copolymer (and) Butylene           Glycol (and) PVM/MA Copolymer           (LUBRAJEL ® OIL BG)           Sodium Polyacrylate   0.75   ISP           (RAPITHIX ® A-100)       B   Octyldodecyl Stearate   3.50   ISP           (CERAPHYL ® ODS)           Isostearyl Neopentanoate   3.50   ISP           (CERAPHYL ® 375)           Diisopropyl Adipate   2.50   ISP           (CERAPHYL ® 230)           Ethylhexyl Palmitate   2.50   ISP           (CERAPHYL ® 368)           C 12-15  Alkyl Lactate   3.00   ISP           (CERAPHYL ® 41)           Glyceryl Stearate (and)   1.25   ISP           Laureth-23 (CERASYNT ® 945)           Peg-20 Stearate (CERASYNT ® 840)   1.00   ISP       C   Cyclopentasiloxane   2.50   ISP           (SI-TEC ™ CM 040)       D   1,3-Butylene Glycol and   0.20   ISP           Iodopropynyl Butylcarbamate           (LIQUAGARD ™)                   100.00%                    
Procedure
 
     1. Combine Phase A except for Rapithix A-100. Sprinkle in Rapithix A-100 with good mixing. 
     2. Combine Phase B with mixing and heat to 70° C. 
     3. When Phase A is uniform and Phase B is at 70° C. slowly add Phase B to Phase A with good mixing. 
     4. When batch is uniform add Phase C with good mixing. 
     5. Add Phase D and mix until the batch is completely uniform. 
     Challenge Tests 
     The challenge test is a 28-day test used to verify the effectiveness of a preservative system in a personal care formulation. Selected personal care formulations were inoculated with microorganisms at the onset of testing (0 hours), then sampled at 48 hours, 7 days, 14 days, 21 days, and 28 days. At 21 days the formulations were re-inoculated with the same microorganisms. Pass/fail criteria were based on modified Cosmetic, Toiletry and Fragrance Association (CTFA) protocol. 
     The invention composition was tested in several systems and found to effectively preserve a variety of personal care formulations against the following microorganisms: 
     
       
         
               
               
               
             
           
               
                   
                   
               
               
                   
                 Microorganism 
                 Abbreviation 
               
               
                   
                   
               
             
             
               
                   
                 
                   Candida albicans 
                 
                 CAN 
               
               
                   
                 
                   Aspergillus niger 
                 
                 AN 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
           
               
                   
               
               
                 Inoculum Concentration (CFU/g) 
               
             
          
           
               
                   
                 Organism 
                 0 Hours 
                 21 Days 
               
               
                   
                   
               
               
                   
                 CAN ATCC 10231 
                 1.9 × 10 6   
                 5.0 × 10 5   
               
               
                   
                 AN ATCC 16404 
                 3.0 × 10 5   
                 1.0 × 10 6   
               
               
                   
                   
               
             
          
         
       
     
                                                       Preservative Efficacy Test Results (CFU/g)            Organism   48 Hrs   7 Days   14 Days   21 Days   28 Days               CAN ATCC   &gt;1.0 × 10 6     &lt;10   &lt;10   1.0 × 10 2     &lt;10       10231       AN ATCC   &lt;10   &lt;10   &lt;10   &lt;10   &lt;10       16404                    
Accordingly this formulation of Example 1 passed a 28-day double challenge efficacy test.
 
     Based on this challenge test data, Liquagard™ is recommended for use in personal care products at levels between 0.1%-0.2% within a broad pH range of 4.0-9.0. 
     EXAMPLE 2 
                                                                 SHOWER GEL            PHASE   INGREDIENT   % W/W   SUPPLIER                    A   Deionized Water   51.45               Disodium EDTA   0.10   Dow Chemical           Polyquaternium-7   2.50   ISP           (CONDITIONEZE ® 7)           Glycerin   2.50           Benzophenone-4   0.20   ISP           (ESCALOL ® 577)       B   Ammonium Lauryl Sulfate   30.00   Rhodia           Cocamidopropyl Betaine   10.00   Goldschmidt           Cocamide DEA   2.50   Cognis       C   PEG-7 Glyceryl Cocoate   0.30   Cognis           Fragrance (#01779396)   0.10   Dragoco           Blue #1 (.1% Aq. Solution)   0.20   Warner Jenkinson       D   1,3-Butylene Glycol and   0.15   ISP           Iodopropynyl Butylcarbamate           (Liquagard ™)                   100.00%                    
Procedure
 
     1. Combine Phase A with mixing and begin heating to 65° C. 
     2. When Phase A is uniform add Phase B in the order listed with mixing. 
     3. Start cooling the batch. 
     4. Add Phases C &amp; D at 30° C. with mixing. 
     5. QS for water loss and mix to RT. 
     pH=7.6 Viscosity=7,200 cps (Brookfield Model RVT, TB @ 5 RPM) 
     
       
         
               
             
               
               
               
               
             
           
               
                   
               
               
                 Inoculum Concentration (CFU/g) 
               
             
          
           
               
                   
                 Organism 
                 0 Hours 
                 21 Days 
               
               
                   
                   
               
               
                   
                 CAN ATCC 10231 
                 4.9 × 10 6   
                 6.6 × 10 6   
               
               
                   
                 AN ATCC 16404 
                 1.0 × 10 6   
                 2.4 × 10 6   
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                   
               
               
                 Preservative Efficacy Test Results (CFU/g) 
               
             
          
           
               
                 Organism 
                 48 Hrs 
                 7 Days 
                 14 Days 
                 21 Days 
                 28 Days 
               
               
                   
               
               
                 CAN ATCC 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 10231 
               
               
                 AN ATCC 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 16404 
               
               
                   
               
             
          
         
       
     
     The formulation of Example 2 passed the 28-day double challenge efficacy test. 
     EXAMPLE 3 
     
         
         PRODUCT: Shower Gel 
         USE LEVEL: 0.02% Liquagard (200 ppm active IPBC) 
       
    
     
       
         
               
               
               
             
           
               
                   
               
               
                   
                   
                 REINOCULUM 
               
               
                 TEST ORGANISM 
                 INOCULUM (0 hours) 
                 (21 days) 
               
               
                   
               
             
             
               
                   Candida albicans  10231 
                 4.9 × 10 6  cfu/g of product 
                 6.6 × 10 6  cfu/g 
               
               
                   Aspergillus niger  16404 
                 1.0 × 10 6  cfu/g of product 
                 2.4 × 10 6  cfu/g 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                   
               
               
                 Assay Interval 
               
             
          
           
               
                 Test Organism 
                 48 Hrs 
                 7 Days 
                 14 Days 
                 21 Days 
                 28 Days 
               
               
                   
               
               
                 
                   Candida albicans 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   Aspergillus niger 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                   
               
             
          
         
       
     
     EXAMPLE 4 
                                                         SCREENING EMULSION            PHASE   INGREDIENT   W/W %                    A   Stearic acid   5.00           Mineral oil   2.50           Cetyl alcohol, NF   1.00           Ceteareth-5   0.50           Glyceryl Stearate and PEG-100 Stearate   1.50       B   DI water   87.90           Triethanolamine (99%)   1.00       C   1,3-Butylene Glycol (and) Iodopropynyl   0.10           Butylcarbamate (LIQUAGARD ™)       D   Citric acid 30% aqueous   0.60                    
Procedure:
 
     1. Heat Phase A to 75° C. Heat Phase B to 75° C. 
     2. Add Phase A to B under moderate sheer with overhead mixer. Remove heat and continue mixing throughout preparation. 
     3. Add Phase C at the appropriate temperature (° C.). 
     4. Add Phase D at 35-40° C. 
     5. Cool to 30-35° C. 
     6. QS with water. Remove contents to a storage container reserving enough in the beaker to measure a pH. Store in refrigerator. 
     EXAMPLE 5 
     Antifungal Efficacy Data 
     
         
         Formulation: Screening Emulsion 
         Liquagard: 10% IPBC in 1,3 butylene glycol 
         Test Method: MLM 100-9 
       
    
     Inoculate formulation at 0 hours. Assay at 48 hours, 7 days, 14 days, 21 days. Re-inoculate at 21 days and then final assay at 28 days. Inoculum counts are listed in Table I. Two levels of Liquagard were tested; the data is contained in Tables II and III below. 
     
       
         
               
               
               
             
           
               
                 TABLE I 
               
               
                   
               
               
                   
                   
                 REINOCULUM 
               
               
                 TEST ORGANISM 
                 INOCULUM (0 hours) 
                 (21 days) 
               
               
                   
               
             
             
               
                   Aspergillus niger  16404 
                 2.0 × 10 5  cfu/g 
                 3.8 × 10 5  cfu/g 
               
               
                 
                   Taloromyces luteus 
                 
                 3.9 × 104 cfu/g 
                 4.0 × 106 cfu/g 
               
               
                   Candida albicans  10231 
                 2.0 × 10 6  cfu/g 
                 1.5 × 10 6  cfu/g 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE II 
               
             
             
               
                   
               
               
                 0.05% Liquagard (50 ppm IPBC) 
               
             
          
           
               
                 Test Organism 
                 48 Hrs 
                 7 Days 
                 14 Days 
                 21 Days 
                 28 Days 
               
               
                   
               
               
                 
                   A. niger 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   T. luteus 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   C. albicans 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE III 
               
             
             
               
                   
               
               
                 0.1% Liquagard (100 ppm IPBC) 
               
             
          
           
               
                 Test Organism 
                 48 Hrs 
                 7 Days 
                 14 Days 
                 21 Days 
                 28 Days 
               
               
                   
               
               
                 
                   A. niger 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   T. luteus 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   C. albicans 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                   
               
             
          
         
       
     
     EXAMPLE 6 
     Liquagard vs Controls 
     
         
         PRODUCT: Screening emulsion 
         USE LEVEL: 100 ppm active IPBC 
       
    
     
       
         
               
               
               
             
           
               
                   
               
               
                   
                   
                 REINOCULUM 
               
               
                 TEST ORGANISM 
                 INOCULUM (0 hours) 
                 (21 days) 
               
               
                   
               
             
             
               
                   Candida albicans  10231 
                 7.2 × 10 6  cfu/g of product 
                 3.0 × 10 6  cfu/g 
               
               
                   Aspergillus niger  16404 
                 1.5 × 10 6  cfu/g of product 
                 7.0 × 10 6  cfu/g 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                   
               
               
                 Assay Interval 
               
             
          
           
               
                 Test Organism 
                 48 Hrs 
                 7 Days 
                 14 Days 
                 21 Days 
                 28 Days 
               
               
                   
               
               
                 Liquagard ™ 
                   
                   
                   
                   
                   
               
               
                 
                   Candida albicans 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   Aspergillus niger 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 Glycacil L* (Lonza) 
               
               
                 
                   Candida albicans 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   Aspergillus niger 
                 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 Unpreserved 
               
               
                 
                   Candida albicans 
                 
                 &gt;1E6 
                 &gt;1E6 
                 &gt;1E6 
               
               
                 
                   Aspergillus niger 
                 
                 &gt;1E6 
                 &gt;1E6 
                 &gt;1E6 
               
               
                   
               
               
                 *Glycacil L - polyethylene glycol monococoate (~40%), polyethylene glycol dicocoate (~40%), 3-iodo-2-propynyl butyl carbamate (~10%) and polyethylene glycol (~10%). 
               
             
          
         
       
     
     EXAMPLE 7 
                                                                 NON-IONIC EMULSION            PHASE   INGREDIENT   % W/W   SUPPLIER                    A   Deionized Water   70.10               PVM/MA Decadiene   0.20   ISP           Crosspolymer (Stabileze ® QM)       B   Ethylhexyl Palmitate   10.00   ISP           (Ceraphyl ® 368)           Cetearyl Alcohol and   2.00   Amerchol           Ceteareth-20 (Promulgen D)           Glyceryl Stearate and   2.50   ISP           Laureth 23 (Cerasynt ® 945)           Isocetyl Stearate   10.00   ISP           (Ceraphyl ® 494)       C   Triethanolamine (99%)   0.20           Deionized Water   qs           1,3-Butylene Glycol and   0.20   ISP           Iodopropynyl Butylcarbamate           (Liquagard ™)                   100.00%                    
Procedure:
         1. Sprinkle Stabileze into water with stirring at RT. Heat phase A to 75° C.       
     2. Combine Phase B, heat to 85° C. 
     3. Combine Phase B to A with stirring, at 75° C. 
     4. When batch is uniform add Phase C. 
     5. When uniform turn off heat. 
     6. Continue stirring thru cool down. 
     7. Make up water loss and stir at RT. Store in refrigerator. 
     EXAMPLE 8 
     Liquagard vs Controls 
     
         
         PRODUCT: Nonionic Emulsion 
         USE LEVEL: 200 ppm active IPBC 
       
    
     
       
         
               
               
               
             
           
               
                   
               
               
                   
                   
                 REINOCULUM 
               
               
                 TEST ORGANISM 
                 INOCULUM (0 hours) 
                 (21 days) 
               
               
                   
               
             
             
               
                   Candida albicans  10231 
                 7.2 × 10 6  cfu/g of product 
                 3.0 × 10 6  cfu/g 
               
               
                   Aspergillus niger  16404 
                 1.5 × 10 6  cfu/g of product 
                 7.0 × 10 5  cfu/g 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
               
             
           
               
                   
               
               
                 Assay Interval 
               
             
          
           
               
                 Test Organism 
                 48 Hrs 
                 7 Days 
                 14 Days 
                 21 Days 
                 28 Days 
               
               
                   
               
               
                 Liquagard ™ 
                   
                   
                   
                   
                   
               
               
                 
                   Candida albicans 
                 
                 3.1 × 10 4   
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 
                   Aspergillus niger 
                 
                 5.0 × 10 4   
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 Control - Glycacil L 
               
               
                 
                   Candida albicans 
                 
                 8.5 × 10 5   
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 3.0 × 10 1   
               
               
                 
                   Aspergillus niger 
                 
                 1.9 × 10 5   
                 &lt;10 
                 &lt;10 
                 &lt;10 
                 &lt;10 
               
               
                 Unpreserved 
               
               
                 
                   Candida albicans 
                 
                 &gt;1.E6 
                 &gt;1E6 
                 &gt;1E6 
               
               
                 
                   Aspergillus niger 
                 
                  &gt;1E6 
                 &gt;1E6 
                 &gt;1E6 
               
               
                   
               
             
          
         
       
     
     In summary, the invention Liquagard™ (ISP) composition can be effectively used in personal care compositions including: 
     Skin Care Compositions 
     Sunscreen creams and lotions; moisturizers; night creams; hand/body creams and lotions; shaving products; cleansing products; wipes; foundations; concealers; body washes; shower gels; liquid hand soaps and baby products. 
     Hair Care Compositions 
     Shampoos, conditioners; deep conditioning treatments; styling gels, mousses, shine lotions, hair colorants and baby products. 
     While the invention has been described with particular reference to certain embodiments thereof, it will be understood that changes and modifications may be made which are within the skill of the art. Accordingly, it is intended to be bound only by the following claims, in which: