Skin cleansing composition

Abstract: Quaternary ammonium salt and bispyridine)-­ polyethylene glycol ester surfactant-betaine and or amine oxide surfactant skin cleansing compositions and method of use thereof are disclosed. The addition of a base amino or ammonium antimicrobial agent (especially bisbiguanide pro­ vide an anti-microbial effect.

Description: Cleansing Composition The invention relates to cleansing compositions having improved sudsing ability for use in washing the skin. The polyethylene glycol or polyoxyethylene esters of fatty acids are a known class of surfactants tW.B. Satkowski, S.K. Huang and R.L. Liss in Nonionic Surfactants, Martin J. Schick, Editor, Marcel Dekker, Inc. New York, 1967, pp. 142-174) of the nonionic type, members of which are listed by trade name (McCutcheon's Detergents & BR< Emulsifiers, North American Edition, McCutcheon Division, MC Publishing Co., 175 Rock Road, Glen Rock, NJ 07452, 1977) and generic name (CTFA Cosmetic Ingredient Dictionary, Second Edition, The Cosmetic, Toiletry and Fragrance Association, Inc., 1133 Fifteenth Street, N.W , Washington, D.C. 20005, 1977). The betaine surfactants are also known and are of the amphoteric type (McCutcheon's Detergents & Emulsifiers, ibid.; CTFA Cosmetic Ingredient Dictionary, ibid.). Members of the class have antimicrobial properties as well as surfactant properties (Seymour S. Block, Disinfection, Sterilization, and Preservation, ibid. pp. 348-360). The amine oxide detergents are also known and are of the nonionic type (AROMOX Amine Oxides, Product Data Bulletin No. 74-21 of Armak Company,Box 1805, Chicago, Illinois, 60690, 1974; McCutcheon's Detergents and Emulsifiers, ibid., CTFA Cosmetic Ingredient Dictionary, ibid.). There is a need for cleansing compositions having improved sudsing ability when compared with the compositions of the prior art. According to the present invention a cleansing composition is provided which contains: (1) from about 0.75% to about 30% by weight of one or more polyethylene glycol ester surfactants having the structural formulas EMI2.1 Formula V Formula VI Formula VII wherein R is alkyl or alkenyl having from about 8 to about 20 carbon atoms or lanolin and n is an iteger from about 8 to about 200; (2) from about 0.5% to about 30% by weight of one or more surfactants selected from a) betaines having the structural formulas EMI2.2 Formula VIII Formula IX EMI3.1 Formula X Formula XI Formula XII wherein R1 is alkyl or alkenyl having from about 8 to about 18 carbon atoms; R2 is methyl, ethyl or 2-hydroxyethyl; R3 is 2-hydroxyethyl or CH2COO R4 is CH2COO or CH2CH2-O CH2COO ; an n is 2 or 3; and b) amine oxides having the structural formula EMI3.2 Formula XIII wherein R1 taken alone is methyl, ethyl or 2-hydroxyethyl; R2 taken alone is methyl, ethyl or 2-hydroxyethyl; R1 and 3. R2 taken together are morpholino; R3 is alkyl having from about 8 to about 18 carbon atoms or R4 CONH(CH2)3 wherein 4. R4 is alkyl having from about 8 to about 18 carbon atoms, and wherein 2-hydroxyethyl can be condensed with from 1 to about 200 units of ethylene oxide; and (3) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an aqueous ethyl alcohol-isopropyl alcohol mixture. The essential ingredients of the cleansing compositions are generally and, in most instances, particularly described by the prior art cited above. The compositions are prepared by conventional methods and in addition to the essential ingredients may also included adjuncts, for sple, emollients, lubricants, sttbilizers, dyes, parfumés and preserva- tives. A suitable acid or base may also be added for pli adjustment. Antimicrobial aryl bisbiguanides (U.S. Pat. 2,684,924; U.S. Pat. 4,053,636) including chlorhexidine t Nerck Index, Ninth Edition, 1976, monograph 2060) and chlorhexidine digluconate salt (U.S. Pat. 2,990,425) are known. U.S. Pat. 3,855,140 describes polyoxyethylenepolyoxypropylene block copolymer cleansing compositions of certain chlorhexidine salts including chlorhexidine digluconate salt. Antimicrobial alkyl bisbiguanides (U.S. Pat. 3,468,898) including alexidine (The Merck Index, ibid., monograph 224) and aqueous compositions thereof with "a compatible surfactant or surfactant mixture selected from the cationic, non-ionic and amphoteric surfactants" (Belgian Pat. 862,808) and cycloalkyl bisbiguanides (U.S. Pat. 4,022,834) are also known. The quaternary ammonium disinfectants (A.N. Petrocci, Disinfection, Sterilization, and Preservation, 2nd Edition, Seymour S. Block, Editor, Lea & Febiger, Philadelphia, 1977, pp. 325-347) are a well-known class of antimicrobial agents. Particularly well-known examples are benzalkonium chloride (The Merck Index, ibid., monograph 1059), benzethonium chloride (ibid., monograph 1078), cetylpyridinium chloride (ibid., monograph 1987), dequalinium chloride (ibid., monograph 2874) and N-myristyl-Nmethylmorpholinium methyl sulfate. Antimicrobial bispyridines and compositions thereof "with any compatible, pharmaceutically acceptable surfactant, preferably a non-ionic surfactant, such as the polyoxyethylene polyoxypropylene copolymers ... amine oxides, such as stearyl dimethyl amine oxide ... or with mixtures of these" are described by British Pat. 1,533,952. Numerous other basic amino and ammonium antimicrobial agents are described by the prior art, as illustrated by the following examples. Amidinoureas are described by U.S. Pat. 4,045,483. U.S. Pat. 3,940,441 describes bisphenoxybenzyldiamines. U.S. Pat. 3,775,477, U.S. Pat. 3,867,454 and U.S. Pat. 4,140,860 describe dioldiamines. The cleansing composition of the present invention can further contain an antimicrobially effective amount of a basic amino or ammonium antimicrobial agent, which can be one or more of the following: a) a compound having the structural formula EMI5.1 Formula I wherein R taken alone is phenyl substituted by alkyl, alkoxy, nitro or halo, p-(2,2-dichlorocyclopropyl) phenyl, alkyl having from 6 to 16 carbon atoms, cycloalkyl or polycyclic alkyl having more than 6 carbon atoms or lower-alkylcycloalkyl or cycloalkyl-lower-alkyl having from 1 to 4 carbons in lower alkyl; R' taken alone is hydrogen; R and R' taken together are 3-azabicylo (3,2,2) nonyl; and n is an integer from 3 to 9; or a pharmaceutically acceptable salt thereof; b) compound having the structural formula or EMI5.2 Formula II Formula III wherein R1 is long-chain alkyl or aralkyl; R2 is short-chain alkyl, long-chain alkyl or aralkyl, benzyl or part of an aromatic system or non-aromatic system; R3 and R4 are shortchain alkyl or part of an aromatic ring system or nonaromatic ring system; Z is an carbon-hydrogen chain; and X is a pharmaceutically acceptable anion; or a c) a compound having the structural formula EMI6.1 Formula IV wherein R is an alkyl group containing from 6 to 18 carbon atoms, a cycloalkyl group containing from 5 to 7 carbon atoms, benzyl, benzyl substituted by one or two substituents selected from the group consisting of halogen, hydroxy, lower-alkyl, lower-alkoxy, nitro, cyano and trifluoromethyl or phenyl substituted by methylenedioxy or one or two substituents selected from the group consisting of halogen, lower-alkyl, lower-alkoxy, nitro, cyano and trifluoromethyl; Y is an alkylene group containing from 4 to 18 carbon atoms and separating the two 4-(R-NH)-l-pyridinyl groups by from 4 to 18 carbon atoms; A is a pharmaceutically acceptable anion; m is 1 or 3; n is 1 or 2; x is 1, 2 or 3; and (m) (2) = (n) (x) Such resulting antimicrobial composition have improved sudsing ability as compared to these of the prior art,e.g., those of U.S. Patent 3,855,140. One can reduce the number of microbes on living skin by applying to the skin an antimicrobially effective amount of any one of the above described antimicrobial cleansing composition. The preferred amount of antimicrobial agent in the composition for skin application is from about 0.01% to about 10% by weight of the composition. In spite of the presence of the antimicrobial agent, a preservative may be necessary to prevent growth of microorganisms in tile antimicrobial atpositions. The adjuncts used in the antimicrobial c positicns 8hould be toeutica1iy accaptable. Particularly preferred bisbiguanides are the following compounds of Formula I. EMI7.1 <tb> Compound <SEP> of <tb> Formula <SEP> R <SEP> R' <SEP> n <tb> Ia <SEP> -ClC <SEP> H5 <SEP> H <SEP> 6 <tb> Ib <SEP> C12 <SEP> CH2 <SEP> C6E5 <SEP> H <SEP> 6 <tb> Ic <SEP> CH3tCH2) <SEP> 3CH(CH2CH3)CH2 <SEP> H <SEP> 6 <tb> Id <SEP> CH3(CH2)6 <SEP> H <SEP> 6 <tb> The compound of Formula Ia is chlorhexidine (The Merck Index, ibid., monograph 2060). The compound of Formula Ic is alexidine (ibid. ,monograph 224). The digluconate salt is a particularly preferred bisbiguanide salt(chlorhexidine gluconate). A particularly preferred quaternary ammonium salt is benzalkonium chloride (ibid., monograph 1059; R is tetradecyl) (Roccal MC-14 Dihydrate:McCutcheon's Detergents and Emulsifiers, ibid., p. 214), which has the structural formula EMI7.2 Formula IIa The following bispyridines of Formula IV are particularly preferred. Compound of Formula R Y A m n x IVa CH3 (cH2) 6 (CH2) 12 C1 or Br 1 2 1 IVb CH3(CH2)7 (CH2) 10 C1 or Br 1 2 1 IVc CH3(CH2) 3CHCH2 (CH2) 12 C1 or Br 1 2 1 CH2CH3 Although any polyethylene glycol ester surfactant of Formula V, Formula VI or Formula VII and any betaine surfactant of Formula VIII, Formula IX, Formula X or Formula XI and any amine oxide surfactant of Formula XII can be used in carrying out this invention, specific members of each class may show advantages in specific application areas. Some that have been commercialized only recently are not listed in the current editions of CTFA Cosmetic Ingredient Dictionary (ibid.) or McCutcheon's Detergents & Emulsifiers (ibid.). Particularly preferred polyethylene glycol ester surfactants are tabulated below. CTFA Cosmetic Ingredient Generic Name Dictionary Page PEG-150 Laurate 219 PEG-150 Distearate 211 PEG-78 Glyceryl Cocoate (Cf. PEG-7 Glyceryl Cocoate) 212 PEG-30 Glyceryl Cocoate (Cf. PEG-7 Glyceryl Cocoate) 212 Particularly preferred betaine surfactants are tabulated below. CTFA Cosmetic Ingredient Generic Name Type Dictionary Page Coco-betaine Formula VIII 67 Coco-sultaine Formula IX 68 Cocamidopropyl Formula X 65 Betaine Cocamidopropyl Formula XI 66 Sultaine Aniphoteric-l Formula XII 24 Particularly preferred amine oxide surfactants are tabulated below. CTFA Cosmetic Ingredient Generic Name Dictionary Page Myristamine Oxide 179 Coco-morpholine Oxide 67 Cocamidopropylamine Oxide 65 Dihydroxyethyl Cocamine Oxide 95 Compatability of the antimicrobial agents of Formula Id, Formula IIa, Formula IVa (A r Br), Formula IVb (A = Br) and Formula IVc (A = Br) with a prototype vehicle of the invention was tested by a serial dilution test against Staphylococcus aureus ATCC 6538. Volumes of two milliliters were used. Dilutions were in tryptose phosphate broth. Incubation was for 16 to 18 hours at 370C. Growth was verified with 2,3,5-triphenyltetrazolium chloride. The inoculum was 1.8 x 105 viable cells per tube. There follows the formula of the prototype vehicle. Ingredient Percent by Weight PEG-150 Laurate 12.0 Isopropyl Alcohol* 3.22 Cocamidopropyl Betaine 3.00 Laneth-16 1.00 Edetate Disodium 0.500 PEG-150 Distearate 0.500 PEG-2M 0.100 Perfume 0.100 FD & Blue No. 1 0.000800 FD & Yellow No. 5 0.000320 Gluconic Acid or Sodium Hydroxide to make pH about 5.5 Purified Water to make 100.0 * To make 4% by volume The following results were obtained. Added Minimum Inhibitory Concentration (MIC) ( g/ml) Vehicle + IIa of Compound of Formula IVc0 (g/ml) Id IIa IVa0 IVb IVc 0 0.25 0.5 0.39 0.5 0.25 15.6 0.25 0.5 0.195 0.5 0.25 31.2 0.25 0.5 0.39 0.5 0.25 62.5 0.25 0.5 0.39 0.5 0.25 125.0 0.25 0.5 0.10 0.5 0.125 250.0 0.25 0.5 0.10 0.25 0.0625 500.0 0.25 0.5 0.10 0.125 0.125 1000.0 0.25 1.0 0.195 0.125 0.125 2000.0 0.50 1.0 0.10 0.125 0.125 4000.0 0.50 1.95 0.195 0.25 0.25 8000.0 0.50 1.95 0.10 0.25 0.25 16000.0 * * * * * 32000.0 ** ** ** ** ** 64000.0 ** ** ** ** ** Expressed as free base o Expressed as cation MIC of vehicle alone ** No growth at this concentration of vehicle It was concluded that each of the five antimicrobial agents tested was compatible with the prototype vehicle. Examples The following examples still more particularly describe the compositions of the invention. Example 1 Ingredient Percent by Weight Chlorexidine gluconate 4.00 PEG-78 Glyceryl Cocoate 10.0 Amphoteric-l 5.00 Laneth-16 1.00 Benzyl Alcohol 1.00 Acetamide MEA 0.750 PEG-30 Glyceryl Cocoate 0.500 Color 0.00100 cont.- Example 1 Perfume 0.0500 Gluconic Acid to make pH about 5.5, about 2.19 Purfied Water to make 100.0 Example 2 Ingredient Percent by Weight Compound of Formula IVb (A=Cl) 2.00 PEG-150 Laurate 12.0 Isopropyl Alcohol 3.22 Cocamidopropyl Betaine 5,00 Laneth-16 1.00 Edetate Disodium 0.500 PEG-150 Distearate 0.500 PEG-2M 0.100 Perfume 0.100 Color 0.00100 Sodium Hydroxide to make pH about 5.5 0,023 Purefied Water to make 100.00 Example 3 Ingredient Percent by Weight Compound of Formula IVb (A=C1) 2.010 PEG-78 Glyceryl Cocoate 10.0 Dihydroxyethyl Cocoamine Oxide 5.00 citric Acid 0.384 Sodium Hydroxide to make pH about 5.5 Purified Water to make 100.t)0 Example 4 Ingredient Percent by Weight Chlorhexidine gluconate 4.00 Amphoteric-l 2.50 Cocamidopropylamine Oxide 2.00 PEG-78 Glyceryl Cocoate 10.0 PEG-30 Glyceryl Cocoate 0.500 Laneth-16 1.00 cont.-Example 4 Acetamide MEA 0.750 Color 0.00100 Perfume 0.0500 Gluconic Acid or Sodium Hy droxide to make pH about 5.5 Acetic Acid 0.500 Benzyl Alcohol 1.00 Purified Water to make 100.00 Example 5 - Ingredient Percent by Weight Chlorhexidine Gluconate 4.00 Dihydroxyethyl Cocamine Oxide 3.00 PEG-150 Distearate 0.750 Laneth-16 1.00 Benzyl Alcohol 2.00 Perfume 0.100 Color 0.00100 Gluconic Acid or Sodium Hydroxide to make pH about 5.5 Purified Water to make 100.00 I'he first ingredient, i.e., the antimicrobial agent, can be omitted in each of the above examples to provide a cleansing composition without substantial antimicrobial effect. The composition of Example 2 was tested for antimicrobial effect on human hands using a gloved-hand model (R.N. Michaud, M.B. McGrath and W.A. Goss, Journal of Clinical Microbiology, vol. 3, 1976, pp. 406-413). Twelve hands were randomly assigned for washes with the composition of Example 2, and twelve hands were randomly assigned for washes witll a corresponding composition differing only by absence of the antimicrobial agent (control). Each hand was washed four times within six hours with a minimum of one hour between washes using five milliliters of each composition for each wash. During each wash the opposite hand of eaoh person was protected with a surgical glove. Iticrobiological samples for quantitative determin ation of aerobic resident bacteria were obtained from each hand immediately prior to the first (Wash 1 Pre), after a glove-wearing period of one hour subsequent to the first (Wash 1 T1), second (Wash 2 T1) and fourth (Wash 4 T1) washes, and after a non-gloving-wearing period of twenty hours after the fourth wash (Wash 4 T20). Total bacterial counts per hand were expressed as logarithms to the base 10. The hand-degerming effect after one wash was evaluated as the bacterial reduction (Wash 1 Pre-Wash 1 T1), abbreviated (W1Pre-W1T1). Cumulative effects after two washes and four washes were evaluated as the bacterial reductions (Wash 1 Pre -Wash 2 T1), abbreviated (WlPre-W2Tl), and (Wash 1 Pre - Wash 4 T1), abbreviated (W1Pre-W4T1). Persistent effect was evaluated as the bacterial reduction (Wash 1 Pre - Wash 4 T20) , abbreviated (W1Pre-W4T20) Microbiological samples were taken by extracting each gloved hand with sampling fluid (100 ml. of 0.1% Triton X-100 in 0.074M phosphate buffer of pH 7.8 + 0.1). An aliquot (10 ml.) of each extract was mixed with chilled neutralizer (10 ml. of 0.0003M potassium dihydrogen phosphate buffer of pH 7.2 containing 2% Tamol N Micro brand of sodium salt of condensed naphthalene sulfonic acid anionic dispersant) . Decimal dilutions (10 1, 10 2 10'3) of the neutralized aliquot were prepared in 0.0003M KH2PO4 buffer, pH 7.2, and were plated in triplicate with trypticase soy agar using the pour-plate technique. Plates were incubated aerobically at- 30 + 20C. for 48-72 hours. A total colony count for each plate was determined using an automated colony counter. Average colony counts were used to estimate the total number of bacteria recovered per hand. The following results were obtained Mean(n=12)Log10 Per of Bacteria Pecovered Per Hand Sample Control Example 2 Wash 1 Pre 6.372 6.165 Wash 1 T1 6.537 5.770 Wash 2 T1 6.316 5.030 Wash 4 T1 5.978 4.296 Wash 4 T20 5.846 4.867 Mean (n=l2) Log10 Bacterial Reductions Per Hand Difference Control Example 2 W1Pre-W1T1 -0.166 0.394 W1Pre-W2T1 0.055 1.135 W1Pre-W4T1 0.393 1.869 W1Pre-W4T20 0.525 1.297 The foregoing mean log10 bacterial reductions were significantly greater (P#0.01) for the hands treated with the composition of Example 2 than for the hands treated with the control composition.

Claims: CLAIMS 1. Cleansing composition characterized by: (1) from about 0.75% to about 30% by weight of one or more polyethylene glycol ester surfactants having the structural Formulas V, VI or VII (herein) wherein R is alkyl or alkenyl having from about 8 to about 20 carbon atoms or lanolin and n is an integer from about 8 to about 200; (2) from about 0.58 to about 30% by weight of one or more surfactants selected from a) betaines having the structural Formulas VI II, IX, X, XI or XII (herein) wherein R1 is alkyl or alkenyl having from about 8 to about 18 carbon atoms; R is methyl, ethyl or 2 hydroxyethyl; P is 2-hydroxyethyl or CH COO; ; R i8 R4is 2 CH2COO or CH2CH2-CH2COO ; and n is 2 or 3; and b) amine oxides having the structural Formula III (herein) wherein RÚ taken alone is methyl, ethyl or 2hydroxyethyl; Rê taken alone is methyl, ethyl or 2hydroxyethyl; RÚ and Rê taken together are morpholino; R3 is alkyl having from about 8 to about 18 carbon atoms or R4 CONH(CH2) 3 wherein R4 is alkyl having from about 8 to about 18 carbon atoms, and wherein hydroxyethyl can be condensed with from about 1 to about 200 units of ethylene oxide. (3) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an aqueous ethyl alcohol-isopropyl alcohol mixture. 2. A composition according to claim 1, characterized by the fact that an antimicrobially effective amount of a basic amino or ammonium antimicrobial agent is present. 3. A composition according to claim 2, characterized by the fact that the amount of antimicrobial agent is from about 0.01% to about 10% by weight of the composition. 4. Composition according to claims 2 or 3, characterized by the fact that the antimicrobial agent is: a) a compound having the structural Formula I (herein) wherein R taken alone is phenyl substituted by alkyl, alkoxy, nitro or halo, p-(2,2-dichlorocyclopropyl) phenyl, alkyl having from 6 to 16 carbon atoms, cycloalkyl or polycyclic alkyl having more than 6 carbon atoms or lower-alkyl-cycloalkyl or cycloalkyl-lower-alkyl having from 1 to 4 carbons in lower alkyl; R' taken alone is hydrogen; R and Ri taken together are 3-azabicylo(3,2,2,) nonyl; and n is an integer from 3 to 9; or a pharmaceutically acceptable salt thereof; b) a compound having the structural Formula I1 or III (herein) wherein R1 is long-chain alkyl or aralkyl; R2 is short-chain alkyl, long-chain alkyl or aralkyl, benzyl or part of an aromatic system or non-aromatic system; R3 and R4 are short-chain alkyl or part of an aromatic ring system or non-aromatic ring system; Z is a carbonhydrogen chain, and X is a pharmaceutically acceptable anion; or c) a compound having the structural Formula IV (herein) wherein R is an alkyl group containing from 6 to 18 carbon atoms, a cycloalky group containing from 5 to 7 carbon atoms, benzyl, benzyl substituted by one or two substituents selected from the group consisting of halogen, hydroxy, lower-alkyl, lower-alkoxy, nitro, cyano and trifluoromethyl or phenyl substituted by methylenedioxy or one or two substituents selected f,om the group consisting of halogen, lower-alkyl, loweralkoxy, nitro, cyano and trifluoromethyl; Y is an alkylene group containing from 4 to 18 carbon atoms and separating the two 4" NH)-l-pyridinyl groups by from 4 to 18 carbon atoms; A is a pharmaceutically acceptable anion; m is 1 or 3; n is 1 or 2; x is 1, 2 or 3; and (m) (2) = (n) (x) 5. A composition according to claim 2, characterized by the fact that the antimicrobial agent is chlorhexidine or a pharmaceutically acceptable salt thereof, 6. A composition according to claim 5, characterized by the fact that the pharmaceutically acceptable salt is the digluconate salt. 7. A composition according to claim 2, characterized by the fact that in the structural formula of the antimicrobial agent R is CH3(CH2)7, Y is (CH2)1O, A is C1 or Br, m is 1, n is 2 and x is 1. 8. A composition according to claim 2, characterized by the fact that the antimicrobial agent is benzalkonium chloride. 9, A composition according to any one of the preceding claims, for reducing the number of microbes on living skin. CLAIMS EMI18.1 1. Cleansing composition characterized by: (1) from about 0.75% to about 30% by weight of one or more polyethylene glycol ester surfactants having the structural Formulas V, VI or VII (herein) wherein R is alkyl or alkenyl having from about 8 to about 20 carbon atoms or lanolin and n is an integer from about 8 to about 200; (2) from about 0.5% to about 30% by weight of one or more surfactants selected from a) betaines having the structural Formulas VIII, IX, X, XI or XII (herein) wherein R1 is alkyl or alkenyl having from about 8 to about 18 carbon atoms; R2 is methyl, ethyl or 2hydroxyethyl; R3 is 2-hydroxyethyl or CH2COO R4 is CH2COO or CH2CH2-O-CH 2COO; and n is 2 or 3; and b) amine oxides having the structural Formula III (herein) wherein R1 taken alone is methyl, ethyl or 2hydroxyethyl; R2 taken alone is methyl, ethyl or 2hydroxyethyl; R1 and R2 taken together are morpholino; R3 is alkyl having from about 8 to about 18 carbon atoms 4 R4CONH(CH2)3 wherein 4 or R CONH(CH2)3 wherein R is alkyl having from about 8 to about 18 carbon atoms, and wherein hydroxyethyl can be condensed with from about 1 to about 200 units of ethylene oxide. (3) water, aqueous ethyl alcohol, aqueous isopropyl alcohol or an aqueous ethyl alcohol-isopropyl alcohol mixture 2. A composition according to claim 1, characterized by the fact that an antimicrobially effective amount of a basic amino or ammonium antimicrobial agent is present. 3. A composition according to claim 2, characterized by the fact that the amount of antimicrobial agent is from about 0.01% to about 10% by weight of the composition. 4. Composition according to claims 2 or 3, characterized by the fact that the antimicrobial agent is: a) a compound having the structural Formula I (herein) wherein R taken alone is phenyl substituted by alkyl, alkoxy, nitro or halo, p-(2,2-dichlorocyclopropyl) phenyl, alkyl having from 6 to 16 carbon atoms, cycloalkyl or polycyclic alkyl having more than 6 carbon atoms or lower-alkyl-cycloalkyl or cycloalkyl-lower-alkyl having from 1 to 4 carbons in lower alkyl; R' taken alone is hydrogen; R and Ri taken together are 3-azabicylo(3,2,2,) nonyl; and n is an integer from 3 to 9; or a pharmaceutically acceptable salt thereof; b) a compound having the structural Formula 11 or III (herein) wherein R1 is long-chain alkyl or aralkyl; R2 is short-chain alkyl, long-chain alkyl or aralkyl, benzyl or part of an aromatic system or non-aromatic system; R3 and R4 are short-chain alkyl or part of an aromatic ring system or non-aromatic ring system; Z is a carbonhydrogen chain; and X is a pharmaceutically acceptable anion; or c) a compound having the structural Formula IV (herein) wherein R is an alkyl group containing from 6 to 18 carbon atoms, a cycloalky group containing from 5 to 7 carbon atoms, benzyl, benzyl substituted by one or two substituents selected from the group consisting of halogen, hydroxy, lower-alkyl, lower-alkoxy, nitro, cyano and trifluoromethyl or phenyl substituted by methylenedioxy or one or two substituents selected from the group consisting of halogen, lower-alkyl, loweralkoxy, nitro, cyano and trifluoromethyl; Y is an alkylene group containing from 4 to 18 carbon atoms and separating the two 4-(R-NH)-l-pyridinyl groups by from 4 to 18 carbon atoms; A is a pharmaceutically acceptable anion; m is 1 or 3; n is 1 or 2; x is 1, 2 or 3; and (m) (2) = (n) (x) 5. A composition according to claim 2, characterized by the fact that the antimicrobial agent is chlorhexidine or a pharmaceutically acceptable salt thereof. 6. A composition according to claim 5, characterized by the fact that the pharmaceutically acceptable salt is the digluconate salt. 7. A composition according to claim 2, characterized by the fact that in the structural formula of the antimicrobial agent R is CH3(CH2)7, Y is (CH2)10, A is C1 or Br, m is 1, n is 2 and x is 1. 8, A composition according to claim 2, characterized by the fact that the antimicrobial agent is benzalkonium chloride.

Inventors: GORMAN, WILLIAM GEORGE, POPP, KARL FREDERICK
Applicants: STERLING DRUG INC.
Application year: 1980
Main classification: C11D3
IPC codes: A61K8, C11D3, C11D1, A61Q19