INSOLUBLE POLYMERIC CONTACT PRESERVATIVES

Abstract: What is disclosed is a method of inhibiting the growth of microorganisms by contacting them with novel insoluble poly­ meric silsesquioxanes having the unit formula [C n H 2n+1 (CH₃)₂N ⁺ / ₋(CH₂) y SiO₃/₂] R where n has a value of 8 to 22, y has a value of 1 to 4, R has a value such that the slsesquioxane is an insoluble, friable solid, and X is chloride, bromide or the -COOH radical.

Description: INSOLUBLE POLYMERIC CONTACT PRESERVATIVES This invention deals with a novel silsesquioxaneand its use to inhibit the growth of microorganisms. It is well known that certain quaternary salts have solution antimicrobial activity and that such salts are active against a fairly broad spectrum of bacteria, fungi, algae and yeasts. The quaternary salts are only a part of a very large collection of soluble reactive chemicals used in many varied applications. An alternative method used for sterilization, preservation or other modes of microbial inhibition has just recently been discovered and has been termed a "surface-bonded" antimicrobial method. Since 1969, there has been a great deal of work in this area of surface bonded functional materials and the published art is fairly extensive. An example of published art in this area is, for instance, "Surface-bonded Antimicrobial Activity of an Organosilicon Quaternary Ammonium Chloride," Isquith, A. J., Abbott, E. A. and Walters, P. A., Appl. Microbiol. 24(6):859-863 (1972). In addition, there exists the physical processes for inhibiting microbial growth such as, ror example, heat, ultraviolet and ionizing radiation and the filtration of the microorganisms by membrane filtration on quantitative sorption on a surface active material packed in a bed. A relatively new approach to the control or microorganisms has been to use insoluble contact antimicrobial materials such as is described in "Prolongation of the Antibacterial Potential of Disinfected Surfaces," Klarmann, E. G., Wright, E. S., and Shternov, V. A., Appl. Microbiol.1:19-23 (1953) and Janauer, G. E. et al, "Insoluble Polymeric Contact Disinfectants: An Alternative Approach to Water Disinfection," Chemistry in Water Rinse, 1:501-521, (1981). Janauer describes this method in terms of the antimicrobial material as being a material that can inactivate or kill target microorganisms by mere contact without adding any reactive agent to the bulk phase being disinfected and further, that the material does not become irreversibly inactivated for further use. The approach, as described by Janauer, is based on inert polymeric materials which allow the incorporation or permanent attachment of germicidal moieties. Janauer, in particular points out the advantages of this type of approach to the varied problems and suggests the following criteria for any truly useful system. The material should be completely water insoluble and the material should not be reactive with it's surroundings such that it is rendered inactive. The material should give instant kill. It should be odorless and tasteless. It should be a broad-spectrum germicide. The biofunctional sites must be easily accessible. The material should retain the germicidal activity for a long time and should not be subject to "exhaustion". It should resist fouling by diverse inorganic and organic matter. Prior to Janauer's disclosure, the next best thing to truly insoluble/nonreactive disinfectants were the "demand-release" disinfectants represented by macroreticular resin compositions impregnated with a silver salt of very low solubility. In spite of the low solubility of the silver salt and means to further reduce the leaching and solubilizing of the silver salt, these compounds add toxic silver to the influents being treated. Janauer, therefore, discloses what he believes to be a truly insoluble polymeric contact disinfectant concept which is the treatment of halomethylated microporous polymers with tertiary amines containing a higher alkyl side chain similar to those found in solution active quaternary salts. Such a material was described by Janauer as the reaction product of halomethylated polystyrene and N,N-dimethyldodecylamine. EMI3.1 One of the major problems cited by Janauer is the inconsistency of the materials produced by this method probably owing to the fact that only 50-60% of the chloromethyl groups are aminated and the interior surfaces of the reticulated polymer have "too much functionalization of the resin interior... (and) a highly functionalized resin may show slower flow rate characteristics." Because of the problems associated with prior art systems, the inventors herein have developed new and novel insoluble contact antimicrobials having use beyond the treatment of water as described by Janauer. The instant invention consists of new and novel silsesquioxanes and their use as antimicrobial agents. What is disclosed, therefore, are silsesquioxanes having the unit formula [CnH2n+1 (CH3)2N+(CH2)ySiO3/2]R wherein n has a value of 8 to 22, y has a value of 1 to 4, R has a value such that the silsesquioxane is an insoluble, friable solid and , X is chloride, bromide or the -COOH radical. What is further disclosed is the use of the silsesquioxanes in a method of inhibiting the growth of microorganisms which method consists of inhibiting the growth of microorganisms by contacting said microorganisms with a polymeric silsesquioxane having the unit formula [CnH2n+1 (CH3)2N+(CH2)ySO3/2] value of 8 to 22, y has a value of 1 to 4, R has a value such that the silsesquioxane is an insoluble, friable solid and, X is chloride, bromide or the -COOH radical. What is finally disclosed is the use of the inventive silsesquioxanes in a cream base, either with or without a medicament. The instant invention, therefore, consists of silsesquioxanes wherein the alkyl substitution on the nitrogen atoms other than two methyl groups consists of CnH2n+l wherein n has a value of 8-22. Preferred for this invention are silsesquioxanes having such an alkyl group wherein n has a value of at least 12. Most preferred for this invention is the silsesquioxane wherein the alkyl group is C18H37. As shown above, y has a value of 1-4. Preferred are those compounds wherein y has a value of 3 or 4. The most preferred compounds are those wherein y has a value of 3. As noted above, the anion of such a silsesquioxane can be chloride, bromide or the -COOH radical. Preferred for this invention are the halides, chlorine and bromine. Most preferred is the chloride ion. Also as noted above, the value of R is such that the silsesquioxane is insoluble and a friable solid. By insoluble, it is meant that the silsesquioxanes are insoluble in water as well as solvents. By being insoluble in solvents, the silsesquioxanes can be made in non-aqueous systems. Obviously, since the silsesquioxanes are not soluble in solvents, they are incapable of being analyzed to acertain their exact structure, however, knowledge of the exact structure of the silsesquioxane is not critical to this invention as long as the silsesquioxane is insoluble and friable. The silsesquioxanes are prepared by known methods. Several methods, for example, are shown in Eaborn, C., "Organosilicon Compounds," Butterworths Scientific Publications, pp. 263-264, (1960). In general, the precursor silane, for example, (R'O)3Si(CH2)YCl-N+R3 is prepared from (R'O)3Si(CH2)YCl and NR3 and then the silane is hydrolyzed in solvent to by-produce an alcohol, corresponding to the (R'O)3- moiety, and the silanol (HO)3Si(CH2)yN R3 C1 which silanol condenses rapidly to increase in molecular weight and form the silsesquioxane. The silsesquioxane is continually heated to further increase the material in molecular weight until a friable solid is obtained. It is such a solid which is the subject of this invention. Because of the insolubility of such a solid, the solid "pops" out of the solution as a slippery mass which upon further work-up becomes white, crystalline-appearing friable particles. In this form, the materials are ready for use in inhibiting microorganisms. The use of these materials for inhibiting microorganisms has great value in the preservation of cosmetics and cream based medicaments. The use of quaternary compounds to concentrate antimicrobial activity at the desired site of action, thus minimizing the amount of chemical agent needed and thus preventing absorption in humans and/or dispersion in the environment has been advantageous. The disadvantage of this kind of immobilization on inert supports has been the use of such compounds only against microorganisms in close proximity to the inert support. This disadvantage can be overcome by utilizing the silsesquioxanes of the instant invention since the silsesquioxanes of the instant invention are their own substrate. These materials are non-absorbable on either oral or dermal exposure in animals. They have wide spectrum antimicrobial activity, particularly against Pseudomonads, they are nontoxic, nonirritating and nonsensitizing. They are odorless, colorless and stable over a wide range of storage conditions. They are easily incorporated in the formulations for cosmetics, burn ointments, ophthalmic solutions and cream based medicaments. Example 1 Preparation of a silsesquioxane. Cl A sample of crude EMI6.1 was stripped under vacuum and recrystallized from hot hexane. This sample (106 gms) was then placed on a rotary evaporator and heated to 900C for three hours. A creamy solid resulted. This solid was dissolved in hot hexane and recrystallized a total of 4 times and three separate crops of the quaternary salt were obtained. This material was a white solid. Amount Chloride equivalent Crop 1 15.2 gms 499.0 Crop 2 8.3 " 491.5 Crop 3 2.8 " 490.0 Theory Chloride 495.6 The above material was dissolved in an equal weight of acetone. Distilled water (300% theory) was added and the mixture refluxed for three hours. A waxy solid formed upon cooling which was filtered from the mixture, rinsed with acetone and air dried. A total of 14.28 gms of cream-colored powder was recovered, a yield of 76% based on a molecular weight of 427 for the hydrolysate. This material was insoluble at a level of 1% in ether, acetone, isopropanol, ethanol, water, toluene, and methylisobutyl.ketone at room temperature. Some limited solubility was apparent in water. A portion (4.4521 gms) of this material was then placed in a Soxhlet extractor for eight hours with 75 mls of distilled water. A total of 3.4091 gms (77%) of water insoluble powder remained in the thimble, and 0.6518 gms of solid was recovered from the water after vacuum evaporation. A second Soxhlet extraction of this material with distilled water resulted in a 96% recovery (3.2621 gms) of the water insoluble powder. Formulations unless specifically produced as sterile products generally contain microorganisms which under most storage conditions can grow and multiply resulting in either an unsafe product (health hazard) or spoilage of the product. Organisms of the genus Pseudomonas, found in a large number of products, are the causative agent of many of these deleterious effects. Compounds described in this invention are particularly active in inhibiting the growth of Pseudomonads. Example 2 Determination of Adequacy of Preservation in a Standard Nonionic Cream. Varying amounts of [C18H37(CH3)2N (CH2)3- SiO3/2Cl JR as prepared above were added to a standard nonionic hand cream for the purpose of testing the preservation adequacy. The following were weighed into a glass beaker: Material Amount Supplier Fisher W-24 Beeswax 12 gms Fisher Scientific Fairlawn, N. J. Atlas Arlacel 83* 12 gms " Atlas G1556** 27 gms Petrolatum*** 45 gms Mineral Oil 225 gms Walgreen U.S.P. (extra heavy) * Sorbitan sesquioleate (HLB) (3.7) ** a blend of nonionic esters (HLB) (11.2) ***Vasoline These materials were heated and stirred at 650C using a magnetic stirrer plate. The antimicrobial was stirred into this part. This combination is part I. A second part (II) was 300 gms of distilled hot water (650C). Twenty three gms of part II at 650C were added to 26.7 gms of 650C part I with rapid stirring. This mixture was stirred until the temperature reached 400C at which point it was allowed to cool to room temperature without stirring. All test formulations were prepared in this manner. Twenty milliliter aliquots of each test formulation were challenged with approximately one million cells of Pseudomonas aeruginosa PRD-10 (ATCC&num;15442) per ml. of formulation. After adding the inoculum, the samples were mixed thoroughly. A one ml. aliquot from each sample was removed, diluted in suitable neutralizing broth, and plated to establish a base line bacterial count at time zero. The samples were stored at 370C and sampled at 3, 7, 14, 21 and 28 days to determine the number of viable organisms remaining in each sample. Table I shows the amount of additive used. Table II shows the results. Thus, it can be observed that under the conditions employed, concentrations of the compound described ranging from 0.01 to 1.00 weight percent acted as an effective preservative in preventing the growth of Pseudomonas. Example 3 Microbial Recovery from Nonionic Hand Creams Preserved with [Ci8H37(CH3)2NC+l(CH2)3 SiO3/2]R and Challenged with Various Strains of Pseudomonas aeruginosa. Various strains of Pseudomonas aeruginosa in a nonionic hand cream as prepared above were tested. The antimicrobial agent was the material prepared in example 1 and was used at 0.33 weight percent based on total solids in the formulation. The results are shown on table III. It can be observed that the antimicrobial agent is effective as a preservative in the nonionic cream against several strains of Pseudomonas aeruginosa. Example 4 Microbial Recovery from Nonionic Hand Creams Containing Various Preservation Agents and Chailer!ged with Pseudomonas aeruginosa ATCC 19660. Table IV shows the results of using several antimicrobial agents of this invention as preservatives in nonionic hand creams. The antimicrobial agents containing dodecyl, tetradecyl and hexadecyl radicals were tested against Pseudomonas aeruginosa ATCC 19660 with good preservative results. The testing was carried out similar to that in examples 2 and 3. Example 5 Preservative action is generally dependent on the solubility of the preservative in the aqueous phase (Rosen, W.E., et. al., "Modern Concepts of Cosmetic Preservation." J. Soc. Cosmet. Chem., 24, 663-675(1973)). The inventive compositions herein are not soluble in water and/or oils. They represent a combination lipophilic/hydrophilic polymer which, although not soluble in either phase, can function as a dispersed particle in either phase. Because of this attribute, the materials are useful in such applications as preservatives in cosmetics, food and feed. These materials are also useful in therapeutic applications such as burn medication, skin antiseptics, post-operative eye medication, antidandruff and athletes foot preparations, soaps, preoperative gastrointestinal sterilization, deodorants, acne preparations, surgical scrubs, laundry detergents, toothpastes, preservation of oils and veterinary care products. Along these lines of applications, the agents of this invention were tested in the following examples. The antimicrobial agents used herein were prepared as in examples 2 and 3. Materials currently used as preservatives that are commercially available were tested in comparison studies. Methyl and propyl parabens (para-hydroxybenzoates) were obtained from D-R Chemical Company, Detroit, Michigan, U.S.A. SilvadeneO (containing 1% silver sulfadlazine) was obtained from Marion Laboratories Kansas City, Mo. Phisohex (3% hexachlorophene) was purchased from Winthrop Laboratories; New York, New York. The antimicrobial agents of this invention as prepared in example 1 and the parabens were tested in a preservative efficacy test by incorporating them into the oil-in-water, non-ionic hand cream formulation of example 2. In this example, forty grams of each test and control formulation containing no additives for preservation were challenged with standardized (lx106 organisms) pure cultures of Pseudomonas aeruginosa ATCC 15442, Pseudomonas aeruqinosaATCC 19660, Staphylococcus aureus ArlCC 6538, Candida albicans ATCC 10231 and Aspergillus niger ATCC 6275. The formulations were subsampled periodically for 28 days to determine the number of surviving microorganisms. The activity of conventional organic quaternary ammonium compounds is generally accepted as reduced against Pseudomonads. Although attractive because of their low toxicity, this weakness in their spectrum of activity has limited the use of organic quaternaries as preservatives in formulations attacked by these organisms. The agents of this invention by contrast, were highly effective against Pseudomonas aeruqinosa ATCC 15442 in oil-in-water, non-ionic formulations while retaining antimicrobial activity against staphylococci, yeast, and fungi. Activity of the inventive agents against Staphylococcus aureus A'l'CC6538 was identified at concentrations of 0.33 and 1.0 weight percent. See Tables V to VIII. Preservative challenge tests conducted with the inventive agents of varying alkyl chain length indicate that the Cl8H37 subsituted agent may be the least active of the series tested. These tests in an oil-in-water ointment indicate a more rapid rate of kill against Pseudomonas aeruginosa ATCC 19660 was achieved with the C12H25 and C14H29 agents. (A) [Cl#(CH3)2N+(CH2)3SiO3/2]R; (B) [Cl#(CH3)2(C12H25)N+(CH2)3SiO3/2]R; (C) [Cl#(CH3)2(C14H29N+(CH2)3SiO3/2]R; (D) 3)2(C16H33)N (CH2)3Sio3/2]R and (E) [Cl#(CH3)2(C18H37)N+(CH2)3SiO3/2]R. See Table IX. Example 6 Burn Therapy The method used to study local therapy of Pseudomonas septicemia in burned mice was similar to that used by Rosenthal "Local and Systemic therapy of Pseudomonas Septicemia in Burned Mice, Annals of Surgery 165: 97-103 (1967). In this preliminary investigation, the antimicrobial agents of this invention were incorporated into a hydrophilic oil-in-water ointment base for application (22% stearyl alcohol, 25% petrolatum, 2% sorbitan monoleate, 1% isopropyl myristate, 12% propylene glycol, 58 polyoxyl 40 stearate, and 33% water). White mice, strain CFW-1 (Carworth, Inc.), Portage, Michigan, were anesthetized with Penthrane (methoxyflurane) manufactured by Abbott laboratories, Chicago, Illinois in a closed chamber. The tail and lower part of the thigh region (approximately 25% of the body surface) were immersed in 70 C water for five seconds. The tail was subsequently challenged with a standardized culture of Pseudomonas aeruginosa ATCC 19660 two hours postburn. Local therapy to the burned area was started six hours postburn and continued for two consecutive days, once per day. The first treatment only was applied to anesthetized mice to allow for longer contact. Mice were observed each day for seven days, deaths recorded, and organ cultures completed from dead animals to confirm Pseudomonas septicemia. Preliminary evaluation of the antimicrobial agent of this invention into a non-ionic ointment indicates activity equivalent to silver sufadiazine in an in vivo test system against a Pseudomonad. Deaths recorded were confirmed by isolation of the test organism from internal organs of necropsied animals. See Table X. Example 7 Surgical Scrub Efficiency Test Potential activity in skin antisepsis was evaluated by the Glove Juice Test as described by Engley and Dey, Engley, F. et. al. Proceedings of the Chem. Spec. Mfg. Assoc. (CSMA), Mid-year meeting (1970) on twenty adult subjects. Following a two week pre-test period where subjects avoided hand contact with antimicrobial or detergent formulations, base-line microbiological counts were established over a one week sampling period. For the actual test, subjects were randomly divided into two groups. One group scrubbed with Phisohex (3 wt. percent hexachlorophene) and the other with 3 wt. percent [Cl8H37(CH3)2N(CH2)3SiO3/2iR in Methocel. Each subject served as their own control by washing the opposite hand under the same conditions with Camay bar soap. Bacterial sampling of the gloved hands, utilizing a neutralizer stripping solution, was at various prescribed time intervals. The test was performed following a single scrub procedure. The data expressed in Table XI below indicates potential utility of the [C18H37(CH3)2N (CH2)3SiO3/2R Cl- as a disinfectant or antiseptic scrub. The actual reduction in microbial counts achieved by both the inventive agent and hexachlorophene are not impressive, however, the data were collected following a single exposure (scrub) to the agents. "The American Type Culture Collection, Catalogue of Strains 1, fifteenth Edition 1982 lists the following strains: Pseudomonas aeruginosa PRD-10 ATCC 15442, page 168; Pseudomonas aeruginosa, ATCC 19660, page 168; Staphylococcus aureus ATCC 6538, page 194; Candida albicans ATCC 10231; page 305; Aspergillus niger ATCC 6275, page 289." Table I Amount of additive in the Formulation + Additive is [C18H37(CH3)2N(CH2)3SiO3/2] Cl Additive %Added (wt./wt.) None (control) 0.00 A 0.01 B 0.033 C 0.10 D 0.15 E 0.25 F 0.33 G 1.00 Table II Microbial Recovery From Nonionic Hand Cream Challenged with Pseudomonas aeruginosa Number of Viable Cells/ml. remaining on sample Day 0 Day 3 Day 7 Day 14 Day 21 Day 28 (control)* 905,000 3,050,000 1,340,000 2,500,000 225,000 470,000 A 650,000 3,550,000 1,550,000 1,500,000 310,000 350,000 B 805,000 4,450,000 1,650,000 1,130,000 315,000 300,000 C 1,270,000 2,700,000 420,000 935,000 305,000 295,000 D 1,060,000 135,000 12,000 3,100 3,500 315 E 1,650,000 215,000 0 0 0 0 F 820,000 2,150 0 0 0 0 G 4,050,000 0 0 0 0 0 * No antimicrobial agent TABLE III MICROBIAL RECOVERY FROM NONIONIC HAND CREAMS PRESERVED WITH [C18H37(CH3)2 NCl#+(CH2)3 SiO3/2]R and Challenged with Various Strains of Pseudomonas aeruginosa Strain of Pseudomonas aeruginosa Control for ATTC 15442 1,700,000 12,300,000 1,950,000 5,200,000 13,900,000 3,200,000 ATTC 15442 2,450,000 138,000 4,250 0 0 0 Control for ATTC 8709 2,450,000 13,300,000 780,000 16,000,000 2,450,000 2,950,000 ATTC 8709 1,850,000 1,000 1,000 0 0 0 Control for ATTC 19660 3,150,000 12,400,000 8,700,000 965,200,000 37,800,000 54,500,000 ATCC 19660 4,850,000 2,000 0 0 0 0 Note: The controls listed are the base hand cream with no preservative and inoculated with said organism. TABLE IV Microbial Recovery from Nonionic Hand Creams Containings Various Preservation Agents and Challenged with Pseudomonae aeruginosa ATCC 19660 Preservation Number of Viable cells/ml. remaining on Agent (0.33% wt./wt.) Day 0 Day 3 + [Cl12H25(CH3)N(CH2)3SiO3/2]R 2,050,500 0 Cl# + [Cl14H29(CH3)2N(CH2)3SiO3/2]R 4,650,500 78,000 Cl# + [Cl16H33(CH3)2N(CH2)3SiO3/2]R 5,100,500 2,200,000 Cl# Control Cream 3,300,000 29,600,000 (No Preservative) TABLE IV (continued) Microbial Recovery from Nonionic Hand Creams Containings Various Preservation Agents and Challenged with Pseudomonae aeruginosa ATCC 19660 Day 7 0 0 0 0 0 0 0 0 1,500 0 0 0 102,000,000 440,000,000 460,000,000 450,000,000 TABLE V [Cl#(CH3)2C18H37N+(CH2)3SiO3/2]R against Pseudomonas aeruginosa Number of Bacterial/ml. of Preparation on: : Weight Percent Sample Day 0 Day 3 Day 7 Day 14 Day 21 Day 28 * Control 9.05 x 105 3.05 x 106 1.34 x 106 2.5 x 106 2.25x105 4.7 x 105 0.15% 1.06 x 106 1.35 x 106 1.2 x 104 3.1 x 10 3.5 x 10 3.15 x 10ê 0.25% 1.65 x 106 2.15 x 105 < 101 < 101 < 101 < 101 0.33% 8.2 x 105 2.15 x 10 < 101 < 101 < 101 < 101 1.0% 4.05 x 106 < 101 < 101 < 101 < 101 < 101 ** 0.15% Methyl Parabens ** 0.03% Propyl Parabens 1.46 x 106 6.15 x 105 2.6 x 104 1.06x 10 7.5 x 10 2.9 x 104 ** 0.3% Methyl Parabens ** 0.06% Propyl Parabens 1.04 x 106 2.55 x 105 8.15 x 104 6.4 x 10 4.0 x 10 2.3 x 104 * No antimicrobial agent ** The methyl and propyl parabens are used in a mixture TABLE VI [Cl#(CH3)2(C18H37)N+(CH2)3SiO3/2]R against Candida Albicans Number of Yeast cells/ml. of preparation on: : Weight Percent Sample Day 0 Day 3 Day 7 Day 14 Day 21 Day 28 * Control 6.75 x 10 6.15 x 104 4.15 x 104 8.35 x 104 5.4 x 104 8.0 x 104 0.25% 1.19 x 104 2.4 x 104 1.0 x 104 1.24 x 10 1.1 x 10ê < 101 0.33% 8.05 x 10 4.29 x 104 5.25 x 10 3.7 x 10ê < 101 < 101 1.0% 5.6 x 10 < 101 < 101 < 101 < 101 < 101 * No antimicrobial agent TABLE VI [Cl#(CH3)2C18H37)N+(CH2)3SiO3/2]R against Staph aureus Number of Bacteria/ml. of preparation on: : Weight Percent Sample Day 0 Day 3 Day 7 Day 14 Day 21 * Control 5.9 x 105 6.05 x 105 6.17 x 105 6.46 x 105 6.92 x 105 0.1% 5.78 x 105 2.4 x 10ê < 101 < 101 < 101 0.33% 5.35 x 105 < 101 < 101 < 101 < 101 1.0% 4.45 x 105 < 101 < 101 < 101 < 101 * No antimicrobial agent TABLE VII [Cl#(CH3)2(C18H37)N+(CH2)3SiO3/2]R against Aspergillus niger Number of fungal spores/ml. of preparation on: : Weight Percent Sample Day 0 Day 7 Day 14 Day 21 Day 28 * Control 1.7 x 105 5.4 x 104 5.75 x 104 3.9 x 104 2.1 x 104 0.25% 1.7 x 105 1.9 x 10 5.0 x 10ê 4.6 x 10ê 4.0 x 10ê 0.33% 1.7 x 105 4.5 x 10 3.0 x 10ê 2.7 x 10ê 2.0 x 10ê 1.0% 1.7 x 105 1.3 x 10 2.0 x 10ê 1.3 x 10ê 1.0 x 10ê * No antimicrobial agent TABLE IX Comparison of Various Silsesquioxanes (Incorporated at 0.33%) Sample Day 0 Day 7 Day 14 Day 21 Control** 3.68 x 106 4.18 x 106 4.79 x 106 5.48 x 106 A*** 6.07 x 105 8.81 x 10 6.29 x 101 -- B 4.26 x 106* < 101 < 101 < 101 C 2.82 x 105* < 101 < 101 < 101 D 6.39 x 105 6.14 x 10 2.74 x 101 < 101 E 3.25 x 106 8.71 x 104 1.27 x 10 1.87 x 101 (B) = *Day 3 < 10 (C) = *Day 3 1.26 x 10ê ** Control contained no antimicrobial at all *** Included for purposes of comparison TABLE X Local Therapy of Pseudomonas septicemia in Burned Mice Treatment Deaths/Group None 5/5 Control ointment 5/5 Cl# 0.33 wt. % [C18H37(CH3)2N+(CH2)3SiO3/2]R 2/5 Cl# 1.0 wt. % [C18H37(CH3)2N+(CH2)3SiO3/2]R 0/5 1.0 wt. % Silver sulfadiazine 0/5 TABLE XI Comparative activity of [C18H37(CH3)2N+(CH2)3SiO3/2]R Cl# with hexachlorophone as a surgical scrub Mean Bacterial Survival/ml. Time after Scrub Control [C18H37(CH3)2N+(CH2)3SiO3/2]R Hexachloropene 1 Minute 49 x 105 7.8 x 105 5.8 x 105 2 Hours 80 x 104 6.2 x 10ê 7.6 x 105 4 Hours 55 x 104 5.3 x 104 3.6 x 104 6 Hours 1.4x 106 4.0 x 106 5.5 x 105

Claims: Claims: 1. A method of inhibiting the growth of microorganisms characterized by contacting said microorganisms with a polymeric silsesquioxane having the unit formula [CnH2n+1(CH3)2N+(CH2)ySiO3/2]R wherein n has a value of 8 to 22, y has a value of 1 to 4, R has a value such that the silsesquioxane is an insoluble, friable solid and, X is chloride, bromide or the -COOH radical. 2. The method of claim 1 wherein the silsesquioxane is combined with a cream base prior to contact with the microorganism. 3. The method of claim 2 wherein the silsesquioxane and cream base also contain a medicament. 4. Silsesquioxane having the unit formula [CnH2n+1(CH3)2N+(CH2)ySiO3/2]R wherein n has a value of 8 to 22, y has a value of 1 to 4, R has a value such that the silsesquioxane is an insoluble, friable solid and, X is chloride, bromide or the -COOH radical. 5. A silsesquioxane as defined in claim 4 wherein n has a value of 12 to 22 and X is chloride. 6. A silsesquioxane as defined in claim 5 which has the unit formula [C12H25(CH3)2N (CH2)3SiO3/2]R Cl 7. A silsesquioxane as defined in claim 5 which has the unit formula [C14H29(CH3)2N+(CH2)3SiO3/2] Cl 8. A silsesquioxane as defined in claim 5 which has the unit formula [C16H33(CH3)2N (CH2)3SiO3/2]R Cl 9. A silsesquioxane as defined in claim 5 which has the unit formula [C18H37(CH3)2N+(CH2)3SiO3/2].

Inventors: GETTINGS, RICHARD LEE, ISQUITH, ALAN JAY
Applicants: DOW CORNING CORPORATION
Application year: 1983
Main classification: A01N55
IPC codes: A61Q17, A01N25, C08G77, A61K8, A01N55