Abstract:
There is provided as a biocide zinc or copper (II) salt having the general formula CH 2 ═C(R 1 )COO-M-OCOC 6 H 3 R 2 R 4 , wherein M is Zn or Cu, R 1  is selected from the group comprising hydrogen and methyl, R 2  is selected from the group comprising hydrogen and OH, R 4  is selected from the group comprising hydrogen, alkyl and SO 2 OH group.

Description:
RELATED APPLICATIONS 
       [0001]    This Application is a Continuation application of International Application PCT/RU2013/000884, filed on Oct. 8, 2013, which is incorporated herein by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention relates to new chemical compounds—zinc and copper salts with organic acids, which can find application as biocides. 
       BACKGROUND OF THE INVENTION 
       [0003]    Various zinc and copper compounds exhibiting biocidal activity are known in the art, in particular, zinc and copper oxides and inorganic salts (RU 95102413, C09D 5/14, 1997; RU 2162870, C09D 5/02, C09D 5/14, 2001; RU 2395548, C09D 5/14, B82B 1/00, 2010; RU 2398804, C09D 5/14, A01N 59/00, A01N 47/00, B82B 1/00, 2010; U.S. Pat. No. 5,540,954, A01N 59/16, A01N 59/20, B27K 3/52, B05D 07/06, A01N 31/08, A01N 31/00, 1996; U.S. Pat. No. 6,858,658, A01N 59/20, A01N 59/16, C09D 5/16, C08K 03/10, C08K 03/18, C08K 03/22, 2005; US 20080219944, C09D 5/16, 2008; US 20090223408, C09D 5/16, C09D 5/14, 2009), zinc and copper naphthenates or resinates (RU 2377121, B27K 3/50, B27K 3/52, B27K 3/22, 2009; EP 2161316, C09D 133/06, C09D 133/12, C09D 143/04, C09D 5/16, C09D 7/12, 2010; EP 2360214, C09D 143/04, C09D 193/04, C09D 5/16, 2011; U.S. Pat. No. 4,258,090, C04B 41/45, C04B 41/52, C04B 41/60, C04B 41/70, B05D 03/02, 1981), ammonia complexes of zinc salts (U.S. Pat. No. 5,460,644, C08K 3/10, C08K 3/00, C09D 5/14, C09D 5/00, 1995), zinc and copper pyrithionates (bis-(2-pyridylthio)-1,1′-dioxides) (RU 2111993, C09D 5/14, C09D 5/16, 1998; RU 2415168, C09D5/16, C09D5/14, 2011; U.S. Pat. No. 5,185,033, C09D 5/14, C09D 5/16, 1993; U.S. Pat. No. 5,298,061, C09D 5/16, C09D 5/14, 1994; U.S. Pat. No. 5,717,007, C09D 5/16, C08L, 33/10, C08K 05/17, C08K 05/18, 1998; U.S. Pat. No. 6,399,560, A01N 43/40, A01N 43/34, A61L 2/18, C11D 3/48, 2002; U.S. Pat. No. 7,410,553, D21C 5/02, B32B 27/04, D21G 1/02, 2008). The above mentioned compounds were used with various degrees of efficiency as additives to coatings intended for treatment of building structures, prevention of underwater structures and ship parts from fouling as well as for paper and wood treatment. 
         [0004]    The closest analogue of the proposed compounds is zinc salt with acetic and methacrylic acids, i.e. zinc methacrylate-acetate (hereinafter referred to as ZMA) exhibiting a certain biocidal activity when compounded with aqueous styrene-acrylic dispersion being used as polymer primer for applying paint coatings to various surfaces (RU 2315793, C09D 5/14, C09D 131/02, C09D 133/10, 2008). 
       SUMMARY OF THE INVENTION 
       [0005]    To provide new means effecting on various biological substrates, there is proposed zinc or copper (II) salt having the general formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0006]    wherein M is Zn or Cu, 
         [0007]    R 1  is selected from the group comprising hydrogen and methyl, 
         [0008]    R 2  is selected from the group comprising hydrogen and OH, 
         [0009]    R 3  is selected from the group comprising alkyl and SO 2 OH group. 
         [0010]    To solve the same problem it is proposed to use as a biocide zinc or copper (II) salt having the general formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0011]    wherein M is Zn or Cu, 
         [0012]    R 1  is selected from the group comprising hydrogen and methyl, 
         [0013]    R 2  is selected from the group comprising hydrogen and OH, 
         [0014]    R 4  is selected from the group comprising hydrogen, alkyl and SO 2 OH group. 
         [0015]    It was surprisingly found that zinc and copper (II) salts corresponding to formula (2) which covers new compounds of formula (1), as well as formerly known zinc acrylate-benzoate and copper methacrylate-benzoate (CN 102167775, 2011), the biocidal activity of which has not been known before, have much higher biocidal activity than ZMA and, besides, wide spectrum of effect on biological matters. Thus, they can be used not only in coating compositions but also in disinfectant compositions of various purpose, paper and wood treatment compositions, polymer compositions with higher fungus resistance as well as in many methods preventing organisms and materials from adverse effect of biological matters. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0016]    The essence of the invention is illustrated by examples given below. Examples 1-8 describe the preparation and properties of certain representatives of the proposed series of substances, examples 9-23—their bactericidal and fungicidal activity. 
       EXAMPLE 1 
       [0017]    10 g of sulfosalicylic acid, 100 ml of distilled water are placed into a 500 ml round-bottom flask and the solution is stirred until sulfosalicylic acid is completely dissolved. Then a suspension of 3.64 g of zinc oxide in 50 ml of distilled water is gradually added to the solution under constant stirring and whereupon 3.2 g of acrylic acid is added and stirred until the suspension is completely dissolved. The obtained solution is evaporated to dryness at a temperature of not more than 70° C., and the resulted solid product is subjected to recrystallization from distilled water, 12.1 g of water-soluble powdered zinc acrylate-sulfosalicylate is obtained which corresponds to the above general formula wherein R 1 ═H, R 2 ═SO 2 OH, R 3 ═OH (79% yield. of the stoichiometric). The results of elemental analysis of salts obtained as described in this and subsequent examples are given in Table 1. 
       EXAMPLE 2 
       [0018]    Zinc methacrylate-benzoate (R 1 ═CH 3 , R 2 ═H, R 3 ═H) with melting point of 283° C. is obtained in 68% yield of the stoichiometric by analogy with Example 1 using benzoic and methacrylic acids instead of sulfosalicylic and acrylic ones (respectively). 
       EXAMPLE 3 
       [0019]    Zinc methacrylate-salicylate (R 1 ═CH 3 , R 2 ═OH) with melting point of 250° C. is obtained in 80% yield of the stoichiometric by analogy with Example 1 using salicylic and methacrylic acids instead of sulfosalicylic and acrylic ones (respectively). 
       EXAMPLE 4 
       [0020]    Zinc methacrylate-sulfosalicylate (R 1 ═CH 3 , R 2 ═SO 2 OH, R 3 ═OH) with melting point of 238° C. is obtained in 82% yield of the stoichiometric by analogy with Example 1 using methacrylic acid instead of acrylic one. 
       EXAMPLE 5 
       [0021]    Zinc methacrylate-toluylate (R 1 ═CH 3 , R 2 ═CH 3 , R 3 ═H) is obtained in 80% yield of the stoichiometric by analogy with Example 1 using toluylic and methacrylic acids instead of sulfosalicylic and acrylic ones respectively). 
       EXAMPLE 6 
       [0022]    Zinc acrylate-benzoate (R 1 ═H, R 2 ═H, R 3 ═H) with melting point of 238° C. is obtained in 55% yield of the stoichiometric by analogy with Example 1 using benzoic acid instead of sulfosalicylic one. The structure of the obtained individual compound is verified by NMR spectra analysis, in NMR spectrum  1 H, multiplets in the regions 5.62÷5.72 and 6.15÷6.30 ppm belong to protons of H 2 C═CH—C(O)O acrylate group. Benzoic group displays signals at δ H  7.38 (triplet), 7.48 (triplet) and 8.06 ppm (doublet). In NMR spectrum  13 C, benzoic group displays signals at δ C  129.0 (m-CH), 131.0 (o-CH), 132.8 (p-CH), 135.2 (C 1 ), 175.4 ppm (OC(═O)), and acrylate group displays signals at δ C  129.0 and 133.2 (H 2 C═CH—), 175.1 ppm (OC(═O)). 
       EXAMPLE 7 
       [0023]    Copper acrylate-benzoate (R 1 ═H, R 2 ═H, R 3 ═H) is obtained in 55% yield of the stoichiometric by analogy with Example 1 using benzoic acid instead of sulfosalicylic one and copper oxide instead of zinc oxide. 
       EXAMPLE 8 
       [0024]    Copper methacrylate-salicylate (R 1 ═CH 3 , R 2 ═H, R 3 ═OH) is obtained in 85% yield of the stoichiometric by analogy with Example 1 using salicylic and methacrylic acids instead of sulfosalicylic and acrylic ones (respectively) and copper oxide instead of zinc oxide. 
       EXAMPLE 9 
       [0025]    Bactericidal activity of zinc methacrylate-salicylate obtained as described in Example 3 and zinc methacrylate-sulfosalicylate obtained as described in Example 4 is determined according to the known method (RU 2378363, C12N 1/00, C12Q 1/00, 2010) based on the exposure of a bacterial culture in a solution of bactericidal substance for a certain period of time followed by its neutralization and inoculation of the culture on a solid nutrient medium. The sensitivity of microorganisms to a disinfectant is judged by microorganism growth on the nutrient medium up to 300 CFU/ml(CFU—colony-forming unit): in particular, growth up to 100 CFU/ml exhibits incomplete bactericidal effect, growth up to 100-300 CFU/ml—sub-bactericidal effect and growth up to more than 300 CFU/ml exhibits resistance of microorganisms to a disinfectant. The determination is performed on  E. coli  No. 906 and  S. aureus  No. 1257 test strains being usually used to study the bactericidal activity of biocides as well as on clinical strains— P. aeruginosa  and methicillin-resistant strain  S. aureus —at salt concentrations from 0.5 to 2% and time of exposure from 5 to 60 min. Test results are given in Table 2. It follows from Table 2 that zinc methacrylate-salicylate at concentration of 1.0% exhibits stable bactericidal effect against all strains at time of exposure from 30 min. At concentration of 2.0%, it exhibits the same bactericidal effect at time of exposure from 5 min. Zinc methacrylate-sulfosalicylate at concentration of 1.0% also exhibits stable bactericidal effect against three of four investigated strains at time of exposure from 30 min. 
       EXAMPLE 10 (COMPARATIVE) 
       [0026]    The same method as described in Example 9 is used to determine the bactericidal activity of ZMA against three of four strains studied in Example 9. Test results are given in Table 3. From Table 3 it follows that the bactericidal activity of ZMA is substantially lower than that of the proposed salts: it exhibits stable bactericidal activity against  E. coli  No. 906 at time of exposure of 30 min. and concentration from 1.0 to 2.5%, not completely stable bactericidal activity against  P. aeruginosa —only at concentration from 2.5%, and sub-bactericidal activity against  S. aureus  No. 1257—only at concentration of 2.5% and time of exposure of 60 min. 
       EXAMPLES 11-23 
       [0027]    The fungicidal activity of the proposed salts is determined according to GOST 30028.4-2006 by testing samples of various materials treated with these salts for resistance to fungal spores. Test results in terms of tolerance time (in days) are given in Table 4 wherein tolerance time for untreated and ZMA-treated materials are given for comparison. It follows from Table 4 that the fungicidal activity of the proposed salts exceeds the fungicidal activity of ZMA. 
       INDUSTRIAL APPLICABILITY 
       [0028]    The present invention can be used for production of biocides intended, for example, for incorporation into polymer materials, disinfectant and antiseptic compositions, treatment of wood, paper, building structures and other materials to prevent their damage caused by biological matters (microorganisms, fungi, algae), manufacture of various articles with biocidal properties, etc. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Results of elemental analysis of salts 
               
             
          
           
               
                   
                 Sample 
                 C, g 
                 H, g 
                 Zn, g 
                 Cu, g 
                 S, g 
               
             
          
           
               
                 Exam- 
                   
                 Empirical 
                 weight, 
                 calcu- 
                 deter- 
                 calcu- 
                 deter- 
                 calcu- 
                 deter- 
                 calcu- 
                 deter- 
                 calcu- 
                 deter- 
               
               
                 ple 
                 Name 
                 formula 
                 g 
                 lated 
                 mined 
                 lated 
                 mined 
                 lated 
                 mined 
                 lated 
                 mined 
                 lated 
                 mined 
               
               
                   
               
             
          
           
               
                 1 
                 Zinc 
                 C 10 H 8 O 8 SZn 
                 0.5 
                 0.170 
                 0.165 
                 0.011 
                 0.012 
                 0.093 
                 0.093 
                   
                   
                 0.045 
                 0.044 
               
               
                   
                 acrylate- 
               
               
                   
                 sulfo- 
               
               
                   
                 salicylate 
               
               
                 2 
                 Zinc meth- 
                 C 11 H 10 O 4 Zn 
                 0.5 
                 0.242 
                 0.25 
                 0.020 
                 0.019 
                 0.120 
                 0.120 
               
               
                   
                 acrylate- 
                   
                   
                   
                 0.24 
                   
                 0.021 
                   
                 0.117 
               
               
                   
                 benzoate 
               
               
                 3 
                 Zinc meth- 
                 C 11 H 10 O 5 Zn 
                 0.5 
                 0.230 
                 0.20 
                 0.0175 
                 0.016 
                 0.114 
                 0.100 
               
               
                   
                 acrylate- 
                   
                   
                   
                 0.21 
                   
                 0.014 
                   
                 0.091 
               
               
                   
                 salicylate 
               
               
                 4 
                 Zinc meth- 
                 C 11 H 10 O 8 SZn 
                 0.5 
                 0.180 
                 0.182 
                 0.0137 
                 0.013 
                 0.089 
                 0.08 
                   
                   
                   
                 0.045 
               
               
                   
                 acrylate- 
                   
                   
                   
                 0.178 
                   
                 0.0135 
                   
                 0.087 
                   
                   
                   
                 0.042 
               
               
                   
                 sulfo- 
               
               
                   
                 salicylate 
               
               
                 5 
                 Zinc meth- 
                 C 12 H 12 O 4 Zn 
                 0.5 
                 0.252 
                 0.25 
                 0.021 
                 0.015 
                 0.114 
                 0.11 
               
               
                   
                 acrylate- 
                   
                   
                   
                 0.265 
                   
                 0.0165 
                   
                 0.116 
               
               
                   
                 toluylate 
               
               
                 6 
                 Zinc 
                 C 10 H 8 O 4 Zn 
                 0.5 
                 0.233 
                 0.24 
                 0.0156 
                 0.015 
                 0.127 
                 0.12 
               
               
                   
                 acrylate- 
                   
                   
                   
                 0.238 
                   
                 0.0165 
                   
                 0.126 
               
               
                   
                 benzoate 
               
               
                 7 
                 Copper 
                 C 10 H 8 O 4 Cu 
                 0.5 
                 0.235 
                 0.24 
                 0.0158 
                 0.0156 
                   
                   
                 0.124 
                 0.125 
               
               
                   
                 acrylate- 
                   
                   
                   
                 0.235 
                   
                 0.016 
                   
                   
                   
                 0.128 
               
               
                   
                 benzoate 
               
               
                 8 
                 Copper 
                 C 11 H 10 O 5 Cu 
                 0.5 
                 0.231 
                 0.21 
                 0.0176 
                 0.0155 
                   
                   
                 0.111 
                 0.115 
               
               
                   
                 meth- 
                   
                   
                   
                 0.205 
                   
                 0.016 
                   
                   
                   
                 0.1 
               
               
                   
                 acrylate- 
               
               
                   
                 salicylate 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Bactericidal activity of zinc methacrylate-salicylate and zink methacrylate-sulfosalicylate 
               
             
          
           
               
                 Concen- 
                 Time of 
                   
                   
               
               
                 tration, 
                 exposure, 
                 Zinc methacrylate-salicylate 
                 Zinc methacrylate-sulfosalicylate 
               
             
          
           
               
                 % wt. 
                 min. 
                   E. coli  1257 
                   S. aureus  906 
                 
                   P. aeruginosa 
                 
                 
                   S. aureus 
                 
                   E. coli  906 
                   S. aureus  1257 
                 
                   P. aeruginosa 
                 
                 
                   S. aureus 
                 
               
               
                   
               
             
          
           
               
                 2.0 
                 30 
                 NG 
                 NG 
                 NG 
                 NG 
                   
                   
                   
                   
               
               
                   
                   
                 NG 
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
               
               
                   
                 15 
                 NG 
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
                 NG 
               
               
                   
                 5 
                 NG 
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
                 NG 
               
               
                 1.0 
                 60 
                 NG 
                 NG 
                 NG 
                 NG 
                 NG 
                 NG 
                 NG 
                 101 CFU 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
                   
                 NG 
                 NG 
                 NG 
                  30 CFU 
               
               
                   
                   
                   
                   
                   
                   
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                   
                   
                   
                   
                 NG 
                 NG 
                 NG 
               
               
                   
                 30 
                 NG 
                 NG 
                 NG 
                 NG 
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                 NG 
                 NG 
                 NG 
                   
                 NG 
                 NG 
                 NG 
               
               
                   
                   
                   
                   
                   
                   
                 NG 
                 &gt;300 CFU 
                 NG 
               
               
                   
                 15 
                 NG 
                 NG 
                 NG 
                    40 CFU 
                 NG 
                 &gt;300 CFU 
                 NG 
               
               
                   
                 5 
                 NG 
                    7 CFU 
                 1 CFU 
                 &gt;300 CFU 
                 NG 
                 CG 
                 1 CFU 
               
               
                 0.5 
                 60 
                 1 CFU 
                 &gt;300 CFU 
                 NG 
                 — 
               
               
                   
                   
                 3 CFU 
                 &gt;300 CFU 
                 3 CFU 
               
               
                   
                 30 
                 &gt;300 CFU    
                 CG 
                 4 CFU 
                 — 
               
               
                   
                 15 
                 42 CFU  
                 CG 
                 10 CFU  
                 — 
               
               
                   
                 5 
                 75 CFU  
                 CG 
                 &gt;300 CFU    
                 — 
               
               
                   
               
               
                 Note: 
               
               
                 NG—no growth; 
               
               
                 CFU—number of colony-forming units in 1 ml; 
               
               
                 CG—confluent growth 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Bactericidal activity of zinc methacrylate-acetate 
               
             
          
           
               
                 Concen- 
                 Time of 
                   
               
               
                 tration, 
                 exposure, 
                 Zinc methacrylate-acetate 
               
             
          
           
               
                 % wt. 
                 min. 
                   E. coli  1257 
                   S. aureus  906 
                 
                   P. aeruginosa 
                 
               
               
                   
               
             
          
           
               
                 5 
                 5 
                 NG 
                 &gt;300 
                 CFU 
                 1 
                 CFU 
               
             
          
           
               
                   
                   
                 NG 
                 &gt;300 
                 CFU 
                 NG 
               
               
                   
                   
                 NG 
                 &gt;300 
                 CFU 
                 NG 
               
               
                 2.5 
                 60 
                 NG 
                 1 
                 CFU 
                 NG 
               
               
                   
                   
                 NG 
                 4 
                 CFU 
                 NG 
               
               
                   
                   
                 NG 
                 95 
                 CFU 
                 NG 
               
               
                   
                 30 
                 NG 
                 &gt;300 
                 CFU 
                 NG 
               
             
          
           
               
                   
                 NG 
                 &gt;300 
                 CFU 
                 1 
                 CFU 
               
             
          
           
               
                   
                 NG 
                 &gt;300 
                 CFU 
                 NG 
               
             
          
           
               
                   
                 5 
                  24 CFU 
                 CG 
                 CG 
               
               
                   
                   
                 113 CFU 
                 CG 
                 CG 
               
               
                   
                   
                 180 CFU 
                 CG 
                 CG 
               
             
          
           
               
                 1.0 
                 60 
                 NG 
                 CG 
                 3 
                 CFU 
               
               
                   
                   
                 NG 
                 CG 
                 93 
                 CFU 
               
               
                   
                   
                 NG 
                 CG 
                 78 
                 CFU 
               
               
                   
                 30 
                 NG 
                 CG 
                 &gt;300 
                 CFU 
               
               
                   
                   
                 NG 
                 CG 
                 &gt;300 
                 CFU 
               
               
                   
                   
                 NG 
                 CG 
                 &gt;300 
                 CFU 
               
             
          
           
               
                   
                 5 
                 CG 
                 CG 
                 CG 
               
               
                   
                   
                 CG 
                 CG 
                 CG 
               
               
                   
                   
                 CG 
                 CG 
                 CG 
               
               
                   
                   
               
               
                   
                 Note: 
               
               
                   
                 NG—no growth; 
               
               
                   
                 CFU—number of colony-forming units in 1 ml; 
               
               
                   
                 CG—confluent growth 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Fungicidal activity of the proposed salts 
               
             
          
           
               
                   
                 Additive 
                   
               
             
          
           
               
                 Example 
                   
                   
                 Content, 
                 Tolerance 
               
               
                 No. 
                 Test material 
                 Name 
                 % wt. 
                 time, days 
               
               
                   
               
             
          
           
               
                 11 
                 Polyvinyl chloride emulsion 
                 Zinc methacrylate- 
                 0.5 
                 16 
               
               
                   
                   
                 salicylate 
               
               
                 12 
                 Polyvinyl chloride emulsion 
                 Zinc methacrylate- 
                 0.5 
                 16 
               
               
                   
                   
                 sulfosalicylate 
               
               
                 13 
                 Polyvinyl chloride emulsion 
                 Zinc acrylate- 
                 0.5 
                 11 
               
               
                   
                   
                 benzoate 
               
               
                 14 
                 Polyvinyl chloride emulsion 
                 Copper methacrylate- 
                 0.5 
                 17 
               
               
                   
                   
                 benzoate 
               
               
                 15 
                 Polyvinyl chloride emulsion 
                 ZMA 
                 5   
                 22 
               
               
                 (compar.) 
               
               
                 16 
                 Polyvinyl chloride emulsion 
                 — 
                 — 
                 6 
               
               
                 (compar.) 
               
               
                 17 
                 Paper impregnated with 
                 Zinc methaerylate- 
                 0.5 
                 8 
               
               
                   
                 latex SKS 65 GP 
                 salicylate 
               
               
                 18 
                 Paper impregnated with 
                 Zinc methacrylate- 
                 0.5 
                 16 
               
               
                   
                 latex SKS 65 GP 
                 sulfosalicylate 
               
               
                 19 
                 Paper impregnated with 
                 ZMA 
                 0.5 
                 12 
               
               
                 (compar.) 
                 latex SKS 65 GP 
               
               
                 20 
                 Paper impregnated with 
                 — 
                 — 
                 4 
               
               
                 (compar.) 
                 latex SKS 65 GP 
               
               
                 21 
                 Paper impregnated with 
                 Zinc methacrylate- 
                 4.7 
                 20 
               
               
                   
                 petrolatum base 
                 sulfosalicylate 
               
               
                 22 
                 Paper impregnated with 
                 ZMA 
                 4.7 
                 16 
               
               
                 (compar.) 
                 petrolatum base 
               
               
                 23 
                 Paper impregnated with 
                 — 
                 — 
                 15 
               
               
                 (compar.) 
                 petrolatum base