US 20040214785A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0214785 A1 Dees et al. (43) Pub. Date: Oct. 28, 2004 (54) SURFACE SANITIZING COMPOSITIONS Publication Classification WITH IMPROVED ANTIMICROBAL PERFORMANCE 51) Int.nt. Cl.Cl." ..................... A61K 31/704; A61K 31/045 A61K 31/14 (75) Inventors: H. Craig Dees, Knoxville, TN (US); (52) U.S. Cl. ............................ 51437; 514/642; 514/717; Eric A. Wachter, Oak Ridge, TN (US) 514/724; 514/200 Correspondence Address: COOK, ALEX, MCFARRON, MANZO, (57) ABSTRACT CUMMINGS & MEHLER LTD SUTE 2850 200 WESTADAMS STREET The present invention is directed to Sanitizing compositions CHICAGO, IL 60606 (US) or preparations comprising of a combination of an alcohol based, Volatile biocide and an additional low-concentration, (73) Assignee: Xantech Pharmaceuticals, Inc. non-volatile antimicrobial agent. In one embodiment of the present invention, the Sanitizer preparation comprises a (21) Appl. No.: 10/796,818 Surface Sanitizing composition or preparation comprised of (22) Filed: Mar. 9, 2004 at least: (1) a biocide comprising a volatile alcohol at a concentration of from greater than or equal to 30% to leSS Related U.S. Application Data than or equal to 70% w/w; and (2) one or more non-volatile antimicrobial agent that is Soluble in Said alcohol at a (60) Provisional application No. 60/453,324, filed on Mar. concentration of from greater than or equal to 0.001% to less 10, 2003. than or equal to 0.1% w/w. US 2004/0214785 A1 Oct. 28, 2004 SURFACE SANTIZING COMPOSITIONS WITH agent was believed to be less effective than hand IMPROVED ANTIMICROBAL PERFORMANCE Washing and was recommended only in emergencies 0001. This application claims the benefit of U.S. provi or in areas where Sinks were unavailable. sional application 60/453,324 filed Mar. 10, 2003. 0007) “In 1975 and 1985, formal written guidelines on handwashing practices in hospitals were pub BACKGROUND OF THE INVENTION lished by CDC. These guidelines recommended 0002 Sanitizing agents containing alcohol and other bio handwashing with non-antimicrobial Soap between cidal components are commonly used to combat contami the majority of patient contacts and washing with nation of Surfaces, Such as human skin, by pathogenic antimicrobial Soap before and after performing inva biological agents, Such as bacteria, fungi and viruses. Sive procedures or caring for patients at high risk. Recently, the U.S. Centers for Disease Control and Preven Use of waterless antiseptic agents (e.g., alcohol tion issued a monograph (i.e., "Guideline for Hand Hygiene based Solutions) was recommended only in situa in Health-Care Settings,” Morbidity and Mortality Weekly tions where sinks were not available. Report, Vol. 51, No. RR-16, dated Oct. 25, 2002, henceforth 0008. “In 1988 and 1995, guidelines for handwash “MMWR/RR-16”) covering this issue; this monograph is ing and hand antisepsis were published by the ASSO hereby incorporated by reference in its entirety. The CDC ciation for Professionals in Infection Control monograph describes how the use of Such Sanitizing agents (APIC). Recommended indications for handwashing has evolved, and usage increased, as it has become clear that were similar to those listed in the CDC guidelines. Simple washing with Soap and water may be inadequate: The 1995 APIC guideline included more detailed 0003 “For generations, handwashing with soap and discussion of alcohol-based hand rubs and Supported water has been considered a measure of personal their use in more clinical Settings than had been hygiene. The concept of cleansing hands with an recommended in earlier guidelines. In 1995 and antiseptic agent probably emerged in the early 19" 1996, the Healthcare Infection Control Practices century. Advisory Committee (HICPAC) recommended that either antimicrobial Soap or a waterleSS antiseptic 0004) “In 1846, Ignaz Semmelweis observed that agent be used for cleaning hands upon leaving the women whose babies were delivered by students and rooms of patients with multidrug-resistant pathogens physicians in the First Clinic at the General Hospital (e.g., Vancomycin-resistant enterococci IVRE) and of Vienna consistently had a higher mortality rate methicillin-resistant Staphylococcus aureus MRSA) than those whose babies were delivered by midwives ). These guidelines also provided recommendations in the Second Clinic. He noted that physicians who for handwashing and hand antisepsis in other clinical went directly from the autopsy Suite to the obstetrics Settings, including routine patient care. Although the ward had a disagreeable odor on their hands despite APIC and HICPAC guidelines have been adopted by Washing their hands with Soap and water upon enter the majority of hospitals, adherence of HCWs to ing the obstetrics clinic. He postulated that the puer recommended handwashing practices has remained peral fever that affected So many parturient women low.” (MMWR/RR-16, pp. 1-2) was caused by “cadaverous particles' transmitted from the autopsy Suite to the obstetrics ward via the 0009 Thus, from its nascence in the mid-19th century, hands of Students and physicians. Perhaps because of the use of Sanitizing agents to combat pathogens has evolved the known deodorizing effect of chlorine com into a commonplace practice by health-care workers, con pounds, as of May 1847, he insisted that students and Sumers, and others concerned about the transmission of physicians clean their hands with a chlorine Solution disease. between each patient in the clinic. The maternal 0010. The majority of antimicrobial agents have been mortality rate in the First Clinic Subsequently designed for use in Sanitizing skin of the hands, and are thus dropped dramatically and remained low for years. formulated as Soaps or lotions, both for Surgical and con 0005 “In 1843, Oliver Wendell Holmes concluded Sumer purposes. Other Such agents have been formulated for independently that puerperal fever was spread by the use elsewhere on the human body, including, for example in hands of health personnel. Although he described the mouth as mouthrinses. measures that could be taken to limit its spread, his 0011. A major component of most such antimicrobial recommendations had little impact on obstetric prac agents is alcohol (Such as ethanol or isopropanol), which tices at the time. However, as a result of the Seminal exhibits potent but transient antimicrobial effects based on Studies by Semmelweis and Holmes, handwashing physical disruption of cells and denaturation of key proteins. gradually became accepted as one of the most impor The MMWR/RR-16 describes these effects as follows: tant measures for preventing transmission of patho gens in health-care facilities. 0012 “The majority of alcohol-based hand antisep tics contain either isopropanol, ethanol, n-propanol, 0006) “In 1961, the U.S. Public Health Service or a combination of two of these products. Although produced a training film that demonstrated hand n-propanol has been used in alcohol-based hand rubs Washing techniques recommended for use by health in parts of Europe for many years, it is not listed in care workers (HCWs). At the time, recommenda TFM as an approved active agent for HCW hand tions directed that personnel wash their hands with washes or Surgical hand-Scrub preparations in the Soap and water for 1-2 minutes before and after United States. The majority of studies of alcohols patient contact. Rinsing hands with an antiseptic have evaluated individual alcohols in varying con US 2004/0214785 A1 Oct. 28, 2004 centrations. Other Studies have focused on combina Like chlorhexidine, tricloSan has persistent activity on the tions of two alcohols or alcohol Solutions containing skin. Its activity in hand-care products is affected by pH, the limited amounts of hexachlorophene, quaternary presence of Surfactants, emollients, or humectants and by the ammonium compounds, poVidone-iodine, triclosan, ionic nature of the particular formulation. Triclosan's activ or chlorhexidine gluconate. ity is not Substantially affected by organic matter, but it can be inhibited by Sequestration of the agent in micelle Struc 0013 “The antimicrobial activity of alcohols can be tures formed by Surfactants present in certain formulations. attributed to their ability to denature proteins. Alco The majority of formulations containing <2% triclosan are hol solutions containing 60%-95% alcohol are most well-tolerated and Seldom cause allergic reactions. Certain effective, and higher concentrations are less potent reports indicate that providing hospital perSonnel with a because proteins are not denatured easily in the triclosan-containing preparation for hand antisepsis has led absence of water . to decreased MRSA infections. Triclosan's lack of potent 0014) “Alcohols have excellent in vitro germicidal activity against gram-negative bacilli has resulted in occa activity against gram-positive and gram-negative sional reports of contamination.” (MMWR/RR-16, p. 16) vegetative bacteria, including multidrug-resistant 0019. Thus, in contrast to alcohols and other biocidal pathogens (e.g., MRSA and VRE), Mycobacterium components of Sanitizers, bacterioStatic agents, like tri tuberculosis, and various fungi. Certain enveloped closan, are thought to Suppress growth of bacteria (except (lipophilic) viruses (e.g., herpes simplex virus, when used at high concentrations, whereupon they are human immunodeficiency virus HIV, influenza capable of exhibiting biocidal properties). It has also been virus, respiratory Syncytial virus, and vaccinia virus) shown in the art that triclosan is a relatively benign antimi are Susceptible to alcohols when tested in Vitro. crobial agent that is principally useful as a bacterioStat, and Hepatitis B virus is an enveloped virus that is Some that topically-applied tricloSan exhibits minimal penetration what less susceptible but is killed by 60%–70% into human skin. alcohol; hepatitis C virus also is likely killed by this percentage of alcohol . .” (MMWR/RR-16, pp. 0020. In addition to antimicrobial Soaps and lotions, an 8-10) additional class of antimicrobial agent is the alcohol-based sanitizer. MMRW/RR-16 notes that “these are typically an 0.015.