Abstract:
A water soluble, antimicrobial composition having antifungal activity useful for disinfecting a contact lens comprise (a) polyhexamethylene biguanide and (b) iodopropynylbutyl carbamate, in a weight ratio of (a):(b) of at least 100:1.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to antimicrobial compositions, and more particularly, to water soluble, antimicrobial compositions of polyhexamethylene biguanide and iodopropynylbutyl carbamate, having antifungal activity, useful as disinfectant solutions for contact lenses. 
     2. Description of the Prior Art 
     Polymeric biguanides such as polyhexamethylene biguanide are known preservatives in aqueous disinfecting solutions used for cleaning contact lenses. While such solutions provide excellent antimicrobial activity, their antifungal activity is limited. Iodopropynylbutyl carbamate, on the other hand, has excellent antifungal activity; however, it is practically insoluble in water, dissolving only 156 ppm at 20° C. 
     Accordingly, it is an object of this invention to provide a water soluble, antimicrobial compositions of polyhexamethylene biguanide and iodopropynylbutyl carbamate, for use as disinfectant solutions for contact lenses. 
     SUMMARY OF THE INVENTION 
     A water soluble, antimicrobial composition having antifungal activity which is useful for disinfecting contact lenses is described herein. The compositions comprise (a) polyhexamethylene biguanide and (b) iodopropynylbutyl carbamate, in a weight ratio of (a):(b) of at least 100:1. 
     DETAILED DESCRIPTION OF THE INVENTION 
     What has been discovered herein is that water insoluble iodopropynylbutyl carbamate (IPBC) is rendered water soluble in the presence of a suitable amount of polyhexamethylene biguanide (PHMB). Normally, IPBC can be dissolved in water only to the extent of 156 ppm at 20° C. However, a combination of PHMB and IPBC, in a weight ratio of 100:1, will permit water dissolution of 2000 ppm of IPBC. 
     The compositions of the invention find particular utility in preserving contact lens solutions. 
     PHMB is commercially available as a 20% active solution under the trade names of Cosmocil® CQ (ICI), Vantocil® IB, Baquacil®. Other trade names for the same chemical are Polysept®, Phogucid® and Renew®. PHMB is a highly effective, nontoxic polymeric antimicrobial preparation; however, its antifungal activity against Aspergillus niger particularly is limited. 
     IPBC is also a commercially available antifungicidal product sold by Troy Chemical under the trade name of Troysan Polyphase® P100, which is 97% active 3-iodo-2-propynylbutyl carbamate. 
    
    
     EXPERIMENTAL 
     1. Preparation of Compositions of Invention 
     Experimental 
     EXAMPLE 1 
     
         ______________________________________PHMB (Cosmocil ® CQ) (20% active)                     200.00(hydrochloride Salt)IPBC (Troysan Polyphase ® P100) (97% active)                     0.41Distilled water           200.00                     400.41  gms______________________________________ 
    
     The composition above was prepared by heating the PHMB solution to 50°-60° C. and adding the IPBC with stirring. Thereupon, most of the IPBC crystals went into solution upon the addition of 200 g of distilled water. The resulting clear solution was cooled to room temperature and the composition was tested for antibacterial and antifungal activity (10% active product). 
     EXAMPLE 2 
     
         ______________________________________Phogucid ® (20% active)                   200    g(Phosphate Salt)IPBC (97% active)       0.4    gWater                   200    g                   400    g______________________________________ 
    
     Procedure: This composition was prepared in the same manner as Example 1. Upon cooling, a small, fine powder (15 mg) precipitated from solution; it was filtered before the solution was submitted for antimicrobial and antifungal activity. 
     2. Solubility of Synergistic Blends of 2% Aqueous Cosmocil® CQ and IPBC 
     
                       TABLE A______________________________________Cosmocil CQ:IPBC        Cos CQ:IPBC IPBC      WaterPercent Ratio        Ratio       (ppm)     Solubility______________________________________99.5:0.5     200:1       100       Soluble99:1         100:1       200       Soluble98.5:1.5     67:1        300       Soluble97.5:2.5     40:1        500       Insoluble 90:10       10:1        2,000     Insoluble______________________________________ 
    
     3. Antimicrobial and Antifungal Activity 
     An in vitro Minimum Inhibitory Concentration (MIC) test was carried out in order to compare Cosmocil CQ and Phoqucid with and without IPBC. 
     Trypticase soy broth (TSB) tubes were diluted for each test material to result in a final test concentration of 1.0%, 0.5%, 0.25%, 0.12%, 0.06%, 0.03%, 0.015%, 0.007%, and 0.003%. 
     Each dilution series was inoculated with these test organisms at the inoculum concentration listed. 
     
         ______________________________________Staph. aureus 6538 (SA)             1.82 × 10.sup.5 cfu/mlE. coli 8739 (EC) 1.0 × 10.sup.5 cfu/mlPs. aeruginosa 9027 (PSA)             5.0 × 10.sup.4 cfu/mlPs. cepacia 25416 (PSC)             4.4 × 10.sup.4 cfu/mlC. albicans 10231 (CA)             1.4 × 10.sup.4 cfu/mlA. niger 16404 (AN)             5.2 × 10.sup.3 cfu/ml______________________________________ 
    
     The bacterial TSB tubes were incubated for 24 hours at 37° C. The yeast and mold tubes were incubated for 48 hours at 27° C. The TSB tubes were examined for positive growth (cloudy tubes). The lowest concentration tested which had a clear (no growth) TSB tube is the static activity concentration. 
     After 24 hours incubation, the bacterial TSB tubes were streaked onto a neutralizing agar media, Letheen agar. A similar procedure was followed after 48 hours incubation with the fungal TSB tubes. The Letheen agar plates were incubated for 48 hours at the required temperature and then checked for growth. The cidal concentration is the lowest concentration exhibiting no growth. 
     The addition of IPBC to both Cosmocil® or Phoqucid® increased the antifungal activity of both compounds. 
     
                       TABLE B______________________________________       Organism*       SA   EC     PsA    PsC   CA   AN______________________________________(A)  2% Cosmocil ®             600    &lt;70  &lt;70  600   600  5000CQ(B)  2% Cosmocial ®             &lt;70    &lt;70  &lt;70  600   30   600CQ + 20 mgIPBC(C)  2% Phoqucid ®             1200   &lt;70  &lt;70  10000 5000 5000(D)  2% Phoqucid ®             600    150  &lt;70  5000  300  30020 mg IPBC______________________________________ 
    
     Table A gives the cidal activity in ppm for each organism for the four test samples.