Disinfectant composition

Abstract

The present invention relates to the use of low concentrations of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof as an emollient in an aqueous disinfectant composition. Aqueous disinfectant compositions and their uses in one or more consumer products and disinfectant methods are also provided.

Description

[Technical Field]

[0001] The present invention relates to disinfectant compositions and their use in consumer products, as well as to methods for disinfecting articles or surfaces using the compositions or consumer products. [Background technology]

[0002] Skin disinfectant or antibacterial compositions are becoming increasingly popular in the healthcare industry and among the general public for their antimicrobial effects. This is especially true after the COVID-19 pandemic, caused by the novel coronavirus 2019-nCoV [officially known as Severe Acute Respiratory Syndrome-Associated Coronavirus SARS-CoV-2].

[0003] Coronaviruses (CoVs) are relatively large viruses containing a single-stranded positive-sense RNA genome enclosed within a membrane envelope. The viral membrane is covered in spikes of glycoproteins, giving coronaviruses their crown-like appearance. There are four classes of coronaviruses: alpha, beta, gamma, and delta. Beta-type coronaviruses include the severe acute respiratory syndrome (SARS) virus (SARS-CoV), the Middle East respiratory syndrome (MERS) virus (MERS-CoV), and SARS-CoV-2, the causative agent of COVID-19. Like SARS-CoV and MERS-CoV, SARS-CoV-2 attacks the lower respiratory tract, causing viral pneumonia. It can also affect the digestive system, heart, kidneys, liver, and central nervous system, potentially leading to multiple organ failure.

[0004] The beta-coronavirus genome encodes several structural proteins, including the glycated spike (S) protein, which functions as a major trigger for the host immune response. This S protein mediates the entry of both SARS-CoV and SARS-CoV-2 into host cells via binding to a receptor protein called angiotensin-converting enzyme 2 (ACE2) on the surface membrane of host cells. According to a 2015 study by Baez-Santos (Antiviral Research (2015), 115, 21-28), this entry process requires priming of the S protein, facilitated by the serine protease TMPRSS211 produced by the host cell. In addition, the viral genome encodes several non-structural proteins, including RNA-dependent RNA polymerase (RdRp), coronavirus major protease (3CLpro), and papain-like protease (PLpro). Upon entering a host cell, the viral genome is released as single-stranded positive RNA. Subsequently, it is translated into viral polyproteins using the host cell's protein translation mechanism, which are then cleaved into effector proteins by viral proteinases 3CLpro and PLpro. PLpro also acts as a deubiquitinating enzyme that can induce immunosuppression by deubiquitinating certain host cell proteins such as interferon factor 3 and NF-κB (Lee et al., Journal of Molecular Biology (2005), 353 (5), 1137-1151). RdRp is used to synthesize a full-length minus-strand RNA template, which is then used by RdRp to produce more viral genomic RNA.

[0005] The interaction between the viral S protein and ACE2 on the host cell surface is of great interest because it initiates the infection process. Cryo-electron microscopy structural analysis has revealed that the binding affinity of the SARS-CoV-2 S protein to ACE2 is approximately 10 to 20 times higher than that of the SARS-CoV S protein (Wrapp et al., Science 2020 Mar 13, 367 (6483);1260-1263; Lu et al., Lancet, 2020 Feb 22;395(10224):565-574). This is thought to be one reason why SARS-CoV-2 has been reported to be more infectious and transmissible than SARS-CoV.

[0006] Alongside the development of therapeutic drugs targeting SARS-CoV-2, there is also considerable interest in compositions that could help prevent infection by viruses and other pathogens through the skin. Specifically, these are compositions that can be easily applied to surfaces and articles and that act efficiently upon application to prevent the spread of infection. This is a particularly challenging issue because SAR-CoV-2, like other known coronaviruses, is an enveloped virus, and enveloped viruses have unique resistances to chemicals and environmental conditions. Desirable formulations for suppressing and killing enveloped viruses such as coronaviruses can be disinfectants, and in particular, disinfectants that exhibit antibacterial activity, virucidal activity and / or sporicidal activity.

[0007] Antibacterial activity can be measured by the BS EN 1500 Hygienic Handrub Method; references to BS EN 1500 herein refer to BS EN 1500:2013. This method is a European standard test method for evaluating the effectiveness of hygienic handrubs by measuring the number of viable bacteria remaining on the fingertips after contamination and exposure to the handrub. Handrub is defined as the process of rubbing hands together without adding water. This method specifically simulates the conditions for determining whether hygienic handrubs reduce the release of transient bacterial flora from the hands.

[0008] Virucidal activity can be measured by BS EN 14476 Chemical disinfectants and antiseptics method; a quantitative suspension test for the evaluation of virucidal activity in the medical area. The reference to BS EN 14476 refers to BS EN 14476:2013+A2:2019. This method is a European standard test method that specifies the minimum requirements for the virucidal activity of chemical disinfectants and antiseptics that form a homogeneous and physically stable formulation when diluted with hard water or in immediate-use products, i.e., products that are not diluted with water at the time of application. This European standard applies to products used in the medical field in the areas of hygienic hand rubbing, hygienic hand washing, disinfection of instruments by immersion, surface disinfection by wiping, spraying, immersion, and other means, and disinfection of textile products. This European standard applies to fields and situations where disinfection is medically indicated. Such adaptations occur in patient care settings such as hospitals, community healthcare facilities, dental clinics, and clinics in schools, kindergartens, and nursing homes, and can also occur in the workplace and at home. This may also include services that directly provide products for patients, such as laundry rooms and kitchens.

[0009] Sporicidal activity can be measured by BS EN 17126 Chemical disinfectants and antiseptics method; a quantitative suspension test for the evaluation of sporicidal activity of chemical disinfectants in medical area. The reference to BS EN 17126 refers to BS EN 17126:2018. This method is a European standard test that specifies the minimum requirements for the sporicidal activity of chemical disinfectants that form a homogeneous and physically stable formulation when diluted with hard water or in the case of immediate-use products. This European standard applies to products used in the medical field for disinfection of instruments by immersion, and for surface disinfection by wiping, spraying, immersion, and other means. This European standard applies to fields and situations where disinfection is medically indicated. Such adaptations occur in patient care settings such as hospitals, community healthcare facilities, dental clinics, and clinics in schools, kindergartens, and nursing homes, and can also occur in the workplace and at home. This may also include services that directly provide products for patients, such as laundry rooms and kitchens.

[0010] Despite significant interest and activity in this field, there is still a need for disinfectant compositions that meet at least one of the aforementioned European standards, particularly compositions that meet all three standards and are effective in killing enveloped viruses such as coronaviruses. Furthermore, in this technical field, such compositions are also required to have limited side effects, especially when used for hand sanitizing. As a result of COVID-19, the frequency and duration of handwashing and hand sanitizing have increased, leading to skin irritation problems, especially since most hand sanitizers rely on the use of alcohol-based solvents.

[0011] The present invention aims to address these needs. [Overview of the project]

[0012] In a first embodiment, the present invention provides the use of 0.001 w / v% to about 0.5 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof as a emollient in an aqueous disinfectant composition. Preferably, the disinfectant composition is a virucidal, antibacterial, or sporicidal disinfectant composition. More preferably, the disinfectant composition is virucidal, antibacterial, and sporicidal. The terms “virucidal,” “antibacterial,” and “sporicidal” are defined herein in accordance with the European standards described above.

[0013] In a second embodiment, the present invention is (a) 0.001 w / v% to approximately 0.5 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or its pharmaceutically acceptable salts and / or solvates; (b) 0.001 w / v% to about 4 w / v% of chlorhexidine or its pharmaceutically acceptable salts and / or solvates; and (c) A disinfectant composition is provided which comprises a disinfectant composition containing 0.001 w / v% to about 2 w / v% of dialkyldimethylammonium chloride (the alkyl group has 8 or more carbon atoms, and the composition is formulated as a single solution in an aqueous solvent).

[0014] In various embodiments of the present invention, the composition preferably comprises 0.001 w / v% to about 0.2 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, more preferably 0.01 w / v% to about 0.1 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof. At such low concentrations, 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline (also known as "HT61") functions as a emollient, which is further described and illustrated herein. HT61 is a compound developed by the applicant, and its synthesis and characterization are disclosed in WO2007 / 054693.

[0015] In various embodiments of the present invention, the composition preferably comprises 0.001 w / v% to about 2 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and more preferably 0.05 w / v% to about 0.5 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof.

[0016] In various embodiments of the present invention, the dialkyldimethylammonium chloride is selected from dioctyldimethylammonium chloride, octyldecyldimethylammonium chloride, and didecyldimethylammonium chloride, and preferably the dialkyldimethylammonium chloride is didecyldimethylammonium chloride, also known as DDAC. In various embodiments of the present invention, the composition preferably contains 0.001 w / v% to about 1 w / v% of didecyldimethylammonium chloride, more preferably 0.01 w / v% to about 0.7 w / v% of didecyldimethylammonium chloride.

[0017] In various embodiments of the present invention, the formulation is biodegradable. The term "biodegradable" means that the disinfectant composition can be decomposed by bacteria and other living organisms, and thus has little environmental impact.

[0018] In various embodiments of the present invention, the aqueous solvent is water.

[0019] In various embodiments of the present invention, the disinfectant composition has virucidal activity measured by BS EN 14476. The virucidal activity of the composition can be specific to picornavirus, poxvirus, coronavirus or a combination thereof. Preferably, the virucidal activity is against poliovirus, poxviruses such as vaccinia virus, coronavirus or a combination thereof. More preferably, the virucidal activity measured by BS EN 14476 is against coronavirus.

[0020] In various embodiments of the present invention, the disinfectant composition has antibacterial activity measured by BS EN 1500. In various embodiments of the present invention, the disinfectant composition is a sporicidal disinfectant composition, and preferably, the composition has sporicidal activity measured by BS EN 17126.

[0021] In a third aspect, the present invention provides a consumer product comprising the disinfectant composition described herein. The consumer product can be, for example, at least one of a disinfectant spray, a hand disinfectant solution or gel, a disinfecting wipe, or a disinfecting pad.

[0022] In a fourth aspect, the present invention provides a method of disinfecting an article or surface, the method comprising treating the article or surface with the disinfectant composition described herein or the consumer product described herein.

[0023] These aspects and embodiments are described in the attached independent and dependent claims. It will be understood that the features of the dependent claims can be combined with each other and with the features of the independent claims in combinations not expressly described in the claims. Furthermore, the approaches described herein are not limited to the specific embodiments shown below, but include and intend to include any combination of the features provided herein. The above and other objects, features and advantages of the present invention will become more fully apparent below by considering the detailed description below.

[0024] For ease of reference, these and further aspects of this disclosure are discussed here under appropriate headings. However, the teachings under each heading are not necessarily limited to each specific heading. [Modes for carrying out the invention]

[0025] While various exemplary embodiments are described or proposed herein, other exemplary embodiments utilizing various methods and materials similar or equivalent to those described or proposed herein are encompassed by the general inventive concept. For the sake of brevity, aspects and features of conventionally practiced embodiments may not be discussed or described in detail. Therefore, it will be understood that aspects and features of apparatuses and methods described herein that are not described in detail may be carried out according to any prior art for performing such aspects and features.

[0026] As used herein and in the claims, the singular forms “a,” “an,” and “the” refer to multiple subjects unless the context clearly indicates otherwise. References to “dry weight percent” or “dry weight basis” refer to the weight of the dry components (i.e., all components except water). The expression “wet weight” refers to the weight of the composition including water or other aqueous solvents. Unless otherwise specified, references to “weight percent” (or “weight %”) of a composition refer to the total wet weight of the composition (i.e., including water or other aqueous solvents).

[0027] In this specification, unless otherwise specified, the term “approximately” modifying the quantity of an ingredient refers to the variation in numerical quantity that may occur, for example, due to typical measurement and liquid handling procedures used in the real world to prepare concentrates or solutions, due to careless errors in these procedures, due to differences in the manufacture, source or purity of the ingredients used, or due to the execution of the method. The term “approximately” also includes different quantities resulting from different equilibrium conditions for compositions arising from a particular initial mixture. Whether modified by the term “approximately” or not, the claims encompass equivalents to quantities.

[0028] The ranges provided herein provide exemplary amounts of each component. These ranges may be used individually or in combination with the ranges of one or more other components.

[0029] The general concept of the invention of this disclosure centers on the use of HT61 as a emollient in aqueous disinfectant compositions. HT61 is disclosed as an antimicrobial compound in WO2007054693A1. Example 1(m) of WO2007054693A1 includes: 1The preparation of chloride salts is included along with the determination of 1H-NMR characteristics. However, HT61 is used at a higher concentration than in the present invention, i.e., 2.0% by weight (see Example 10), in formulations that are not aqueous disinfectant compositions and have been tested for physiological activity against bacteria in the logarithmic and quiescent phases. WO2007054693A1 does not teach that HT61 has any function at much lower concentrations, i.e., 0.001% w / v to 0.5% w / v, nor does it suggest that this compound functions well in aqueous disinfectant compositions as discussed herein.

[0030] Emulsifiers support the skin's barrier function, creating a protective layer on the skin's surface to prevent moisture loss. They can also replenish moisture by drawing it into the uppermost layer of the skin and retaining it. Thus, the functions of emollients include softening, moisturizing, lubrication, protection, film formation, conditioning, solubilization, and dispersion. The emollient properties of HT61 have been demonstrated and further discussed in the examples. These properties are advantageous in the field of aqueous disinfectants for topical use due to the aforementioned problems of skin irritation and dermatitis.

[0031] More specifically, the concept of the present invention focuses on using HT61 as a emollient in an aqueous disinfectant composition that is formulated as a single solution and is therefore easy to manufacture. This disinfectant composition comprises a specified amount of chlorhexidine and a specified amount of dialkyldimethylammonium chloride and exhibits advantageous antibacterial, virucidal, and / or sporicidal activity in one or more of the European Standard tests described above.

[0032] Chlorhexidine is a commercially available preservative compound. In Europe, it is sold under various brand names for a range of therapeutic applications. For example, Corsodyl (registered trademark) is a mouthwash containing chlorhexidine digluconate (0.2 w / v%) and is indicated for inhibiting plaque formation as an adjunct in the treatment and prevention of gingivitis and in maintaining oral hygiene.

[0033] However, when used as a disinfectant, particularly as a skin disinfectant, chlorhexidine is typically used in an alcoholic solvent. For example, Vesismin Health's Bactiseptic Orange is a disinfectant formulated with a solution of 2% chlorhexidine and 70% isopropyl alcohol. Similarly, RU2724581C1 discloses disinfectants containing, in particular, 40-50% n-propyl alcohol, 10-30% isopropyl alcohol, and 0.4-0.6% chlorhexidine bigluconate. However, the use of such high levels of alcohol is undesirable due to the risk of drug abuse by consumers and the side effects of using such products on the skin, such as skin irritation and dermatitis.

[0034] Dialkyldimethylammonium chlorides having eight or more carbon atoms in an alkyl group include didecyldimethylammonium chloride or DDAC, which are commercially available disinfectants and used in a variety of biocidal applications. DDAC, like chlorhexidine, is typically used in alcoholic solvents. For example, K-CARE® DDAC80 contains up to 20% ethanol along with 78-82% DDAC.

[0035] In this invention, a combination of 0.001 w / v% to 0.5 w / v% HT61 or a pharmaceutically acceptable salt and / or solvate thereof, 0.001% to 4% chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and 0.001 w / v% to 2 w / v% dialkyldimethylammonium chloride, such as DDAC, can be formulated as a single solution in an aqueous solvent, which advantageously provides activity against enveloped viruses. This activity can be antibacterial, virucidal, and / or sporicidal, and may include inhibition and killing of viruses.

[0036] As used herein, the terms “disinfection” and “disinfectant” have meanings understood by those skilled in the art in the medical field. In particular, they refer to the killing of (theoretically all) pathogenic bacteria harmful to humans. The activity of disinfectant compositions can be measured by one or more of the European standard test methods described above: BS EN 14476, BS EN 1500, and BS EN 17126. Each of these test methods is incorporated herein by reference. As described above, each of these test methods is a European test standard. This means that each test is approved by the European Committee for Standardization (CEN).

[0037] The BS EN 14476 standard requires that chemical disinfectants achieve a reduction in viral titer of at least 4.0 log against one or more specified microorganisms. For surface disinfection, these microorganisms include poliovirus (poliovirus type 1, LSc 2ab), norovirus (mouse norovirus, S99 Berlin strain), and adenovirus (adenovirus type 5, adenoid 75 strain, ATCC VR-5). For hygienic hand rubbing and hand washing, these microorganisms include poliovirus (poliovirus type 1, LSc 2ab) and vacciniavirus (modified vacciniavirus Ankara, ATCC VR-1508, or vacciniavirus strain Elstree, ATCC VR-1549), with the latter exhibiting virucidal activity against enveloped viruses and the former exhibiting virucidal activity against non-enveloped viruses.

[0038] All viruses listed in the BS EN 14476 standard, with the exception of vaccinia virus, are non-enveloped viruses and therefore have higher resistance to chemical disinfectants. Poliovirus is the most resistant of the listed non-enveloped viruses; therefore, in this invention, the efficacy and activity against poliovirus are used to demonstrate virucidal activity against non-enveloped viruses, while the efficacy and activity against vaccinia virus are used to demonstrate virucidal activity against enveloped viruses (including coronaviruses).

[0039] As described in the BS EN 14476 standard (incorporated herein by reference), in preparation for the suspension test, the test virus is added to the interfering substance in the suspension. The selection of the interfering substance used in the test depends on the required product. For sanitary hand sanitizers and handwashing, the interfering substance is 0.3 g / L bovine albumin (clean state; sanitary hand sanitizer) or 3.0 g / L bovine albumin solution and 3.0 mL / L red blood cells (contaminated state; sanitary handwashing). Next, the test substance or test disinfectant is added to the virus suspension for an exposure period at the temperature specified by the manufacturer (e.g., 20°C or 4°C to 30°C, with a contact time of 30 seconds to 2 minutes, 5 minutes, or 60 minutes). After the exposure time, the sample is collected and the activity of the test substance is neutralized by dilution with ice-cold test medium. Sequential dilutions are performed to examine the viral infectivity of the dilutions. Unlike bacteria and fungi, most viruses are too small to be observed with a light microscope (in the range of 25 nm to 400 nm). Therefore, the presence or absence of the virus in the suspension before and after product exposure is measured by inoculating the suspension into viable host cells. Next, structural changes in these cells are observed after 7 days (depending on the cell type). If the test product fails to inactivate the test virus before neutralization, the test virus will invade and damage viable cells, exhibiting a cytopathic effect (CPE). These are effects that virologists observe when examining cells with a light microscope.

[0040] BS EN 1500 is a European standard test method for evaluating the effectiveness of sanitary hand sanitizer by measuring the number of viable bacteria remaining on fingertips after contamination and hand sanitizer exposure. In this test, subjects with healthy hands are randomly assigned either a reference control product or a sanitary hand sanitizer under evaluation. After washing with mild soap to remove natural, temporary microorganisms, the subjects' hands are thoroughly dried with a paper towel.

[0041] Typically, this test method uses a prepared pure culture of non-pathogenic E. coli, such as non-pathogenic E. coli K12 (e.g., NCTC 10538), as the inoculant. The subject immerses their hand in a predetermined volume of inoculant up to the center of the wrist for 5 seconds, with their fingers spread. After that, the hand is air-dried for 3 minutes, and a sample is taken by rubbing the fingertip in a petri dish containing sterile trypsin-soybean broth (TSB) to measure the preliminary number of viable bacteria present in the hand.

[0042] Immediately after pre-value sampling, the hand is re-inoculated, and either a standard hand rubbing procedure using 60% (v / v) propan-2-ol or a sanitary hand rubbing procedure tested according to the manufacturer's instructions is performed. Subsequently, fingertips are sampled for post-values ​​in the same manner as pre-values, this time using a TSB containing a chemical neutralizing agent. The samples are then appropriately diluted, seeded on trypsin-soybean agar (TSA) medium, incubated at 36±1°C for 18–24 hours, counted, and re-incubated for a further 24 hours to detect potentially slow-growing colonies.

[0043] Prior and post-exposure values ​​collected from fingertips are evaluated relative to each other to obtain a ratio called the reduction coefficient. The reduction coefficient provides a quantitative measure of the antimicrobial effect. This is determined by comparing the average count of viable microbial colony-forming units in the prior state with the average count after exposure to the sanitary hand sanitizer. The average reduction in the release of the test organism Escherichia coli (E. coli) K12 achieved by sanitary hand sanitizing with the test product should be at least as good as that achieved with a standard hand sanitizer (60% by volume propane-2-ol).

[0044] BS EN 17126 is a European standard that specifies test methods and minimum requirements for evaluating the spore-canceling activity of chemical products that become homogeneous and physically stable formulations when diluted with hard water, or with water in the case of immediate-use products. To be characterized as a spore-canceling agent, the product must demonstrate a decrease of at least 4 on a decimal logarithm when tested in accordance with BS EN 17126.

[0045] For surface disinfection, the spore-killing activity in BS EN 17126 is used for Clostridium difficile R027 (NCTC 13366) and / or Bacillus subtilis (ATCC 6633) and Bacillus cereus (CIP). For product 105151), the test is performed at a test temperature range of 4°C to 30°C. A sample of the product in its received state and / or diluted with hard water (or water for immediate use products) is added to a test suspension of spores in a solution of interfering substances (e.g., 0.3 g / L bovine albumin solution for clean conditions, and 3.0 g / L bovine albumin solution + 3.0 mL / L red blood cells for contaminated conditions). This mixture is maintained at the test temperature for a maximum contact time of 15 minutes or 60 minutes, depending on the actual conditions of the product. Products intended for disinfecting surfaces that may come into contact with patients and / or medical staff, and surfaces that are frequently touched by different people and could lead to microbial transmission to patients, are tested for a maximum contact time of 15 minutes. Products for other surfaces can be tested for a maximum contact time of 60 minutes. After the contact time, a small sample is taken and the sporicidal activity in this portion is immediately neutralized or inhibited by a validated method. The method of choice is dilution neutralization. The number of viable spores in each sample is determined and the decrease is calculated.

[0046] In various embodiments of the present invention, the disinfectant composition is effective in reducing the concentration or killing one or more enveloped viruses or non-enveloped viruses. In various embodiments, the disinfectant composition is effective in reducing the concentration or killing one or more non-enveloped viruses such as poliovirus and / or one or more enveloped viruses such as vaccinia virus, coronavirus and combinations thereof. In various embodiments, the disinfectant composition is effective in reducing the concentration or killing one or more enveloped viruses such as vaccinia virus, coronavirus and combinations thereof.

[0047] Viruses are tiny infectious organisms consisting of nucleic acids (DNA / RNA) in a protein coating that infects the cells of living organisms. Viruses replicate by causing host cells to copy their genetic material, and are classified into two types based on the composition of their outer surface structure: enveloped viruses and non-enveloped viruses. Enveloped viruses have a protein coating, often called a capsid, which is further enclosed by an outer lipid membrane. The lipid membrane contains phospholipids, proteins, and viral glycoproteins, and the glycoproteins allow the virus to identify and attach to receptor sites on the host cell membrane. Conversely, non-enveloped viruses are surrounded only by a protein coating (capsid) that performs the task of attaching to the host cell. Unlike enveloped viruses, non-enveloped viruses are typically resistant to a wide range of harsh environmental conditions, including heat, dryness, and acidity. In fact, non-enveloped viruses can survive some disinfection processes and maintain sufficient activity / infectivity. Therefore, these characteristics make it particularly difficult to kill and suppress non-enveloped viruses.

[0048] In various embodiments of the present invention, the disinfectant composition is effective in reducing or killing the concentration of one or more viruses selected from poliovirus, coronavirus, or combinations thereof. In various embodiments, the composition may be effective against enveloped viruses (as indicated by its activity against vaccinia virus). In various embodiments, the disinfectant composition is effective against poliovirus. In various embodiments, the disinfectant composition is effective against vaccinia virus. In various embodiments, the disinfectant composition is effective against coronavirus. In various embodiments, the disinfectant composition is effective against both poliovirus and vaccinia virus. In various embodiments, the disinfectant composition is effective against each of poliovirus, vaccinia virus, and coronavirus. The term "effective against" means a reduction in the concentration of the virus.

[0049] The poliovirus is the causative virus of poliovirus infection (polio), a highly contagious viral disease transmitted horizontally. Three serotypes of poliovirus have been identified: PV1, PV2, and PV3, each exhibiting a different capsid protein. Complications from polio include muscle weakness, paralysis, and, in some cases, death. As mentioned above, the poliovirus is a well-studied non-enveloped virus and exhibits similar drug resistance to a wide variety of other human viruses; therefore, it is used as a standard in the measurement of viricidal activity in EN14476.

[0050] Coronaviruses are a group of closely related RNA viruses that cause disease in mammals and birds. In humans, these viruses cause respiratory infections that can range from mild to lethal. They are enveloped viruses with a positive-sense single-stranded RNA genome and a helical nucleocapsid. In various embodiments of the present invention, the disinfectant composition is effective against coronaviruses, specifically feline coronavirus according to the BS EN 14476 protocol. Feline coronavirus (FCoV) is a positive-sense RNA virus that infects cats worldwide. It is a coronavirus of the alphacoronavirus 1 species, which includes canine coronavirus and porcine gastroenteritis coronavirus. Feline coronavirus is known in the art and is widely accepted as a substitute for SARS-CoV-2. Therefore, activity against FCoV can be extrapolated to activity against SARS-CoV-2.

[0051] In various embodiments, the disinfectant composition statistically reduces the concentration of enveloped viruses such as vaccinia virus and / or coronavirus, and / or non-enveloped viruses such as poliovirus, by a statistically significant amount, and in other embodiments, it meets the EN14476 standard for enveloped and / or non-enveloped virus concentrations. The expression "statistically significant" means that the test composition has a p < 0.05 ratio with respect to a control that does not contain the active ingredient. The analysis is performed using 1) a t-test (statistical examination of the means of two populations); or 2) analysis of variance (ANOVA) when comparing two or more test samples against controls.

[0052] In various embodiments, the disinfectant composition exhibits antibacterial activity according to the BS EN 1500 protocol.

[0053] In various embodiments, the disinfectant composition exhibits spore-killing activity according to the BS EN 17126 protocol. Such activity may involve reducing the amount of Clostridium difficile on an article or surface.

[0054] As used herein, the term “pharmaceutically acceptable derivative” means the following: (a) pharmaceutically acceptable salts; and / or (b) Solvates (such as hydrates)

[0055] Suitable acid addition salts include carboxylates (e.g., formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprirate, caprylate, stearate, acrylate, caproate, propionate, ascorbate, citrate, glucuronate, glutamate, glycolate, α-hydroxybutyrate, lactate, tartrate, phenylacetate, mandelate, fenlpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate) Examples include salts (e.g., suberate, sebacinate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate, or terephthalate), halide salts (e.g., chloride salts, bromide salts, or iodide salts), sulfonates (e.g., benzenesulfonate, methyl-, bromo- or chlorobenzenesulfonate, xylenesulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, 1- or 2-naphthalenesulfonate, or 1,5-naphthalenedisulfonate), or sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monophosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, or nitrates.

[0056] Suitable base salts include metal salts, such as sodium salts, calcium salts, and amine salts.

[0057] The present invention also includes, where appropriate, all enantiomers and tautomers of the said compounds. Compounds having optical properties (one or more chiral carbon atoms) or tautomeristic features will be identifiable to those skilled in the art. Corresponding enantiomers and / or tautomers can be isolated or produced by methods known in the art.

[0058] Some of the compounds included in the composition of the present invention can exist as stereoisomers and / or geometric isomers. For example, since they can have one or more asymmetric centers and / or geometric centers, they can exist in two or more stereoisomeric forms and / or geometric isomeric forms. The present invention contemplates the use of all individual stereoisomers and geometric isomers of these inhibitors, as well as mixtures thereof. The terms used in the claims encompass these forms, provided that they retain the appropriate functional activity (although not necessarily to the same extent).

[0059] The present invention also encompasses all suitable isotopic forms of the compound or its pharmaceutically acceptable salts. Isotopic forms or their pharmaceutically acceptable salts are defined as those in which at least one atom is replaced by an atom having the same atomic number but a different atomic mass than that usually found in nature. Examples of isotopes that can be incorporated include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as 2 H, 3 H, 13 C, 14 C, 15 N, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F and 36 Cl. Certain isotopic forms, such as those incorporating radioactive isotopes such as 3 H or 14 C, are useful in studies of the tissue distribution of drugs and / or substrates. Tritiation, i.e., 3 H, and carbon-14, i.e., 14 C, isotopes are particularly preferred because they are easy to produce and detectable. Furthermore, substitution with isotopes such as 2 H, deuterium, may provide certain therapeutic advantages, such as an increase in the in vivo half-life or a reduction in the required dose, due to increased metabolic stability, and may be preferred in certain situations. Isotopic forms can be produced by conventional procedures using appropriate isotopic forms of suitable reagents.

[0060] The compounds used in the compositions of the present invention, which include pharmaceutically acceptable derivatives, are commercially available and / or can be produced by synthetic methods known in the art.

[0061] 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline and its pharmaceutically acceptable salts and / or solvates can be prepared according to the synthetic methods shown, for example, in WO2007 / 054693A1, and these methods (e.g., Examples 1 and 9) are incorporated herein by reference. To avoid misunderstanding, the name 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline refers to the compound having the following chemical structure:

[0062] [ka]

[0063] Preferred pharmaceutically acceptable derivatives of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline include its hydrochloride and mesylate salts.

[0064] Chlorhexidine is a cationic polybiguanide, also known as N,N''''1,6-hexanediyrbis[N′-(4-chlorophenyl)(imidodicarbonimidodiamide)], which has the following chemical formula.

[0065] [ka]

[0066] Chlorhexidine and its pharmaceutically acceptable salts and / or solvates are commercially available, for example, from Sigma Aldrich Limited. Preferred pharmaceutically acceptable salts of chlorhexidine include its hydrochloride, dihydrochloride, diacetate, acetate, digluconate, and gluconate. Particularly preferred salts are diacetate and digluconate, and especially chlorhexidine digluconate.

[0067] The group of compounds included in dialkyldimethylammonium chloride (where the alkyl group has eight or more carbon atoms) is known in the art and can be produced by known synthetic methods or obtained from commercial sources. Dialkyldimethylammonium chloride can be selected from didecyldimethylammonium chloride, dioctyldimethylammonium chloride, distearyldimethylammonium chloride, octyldecyldimethylammonium chloride, and dimethyldioctadecylammonium chloride. Preferably, dialkyldimethylammonium chloride is selected from didecyldimethylammonium chloride, dioctyldimethylammonium chloride, and octyldimethylammonium chloride. More preferably, dialkyldimethylammonium chloride is didecyldimethylammonium chloride or DDAC having the following chemical structure.

[0068] [ka]

[0069] Dialkyldimethylammonium chloride is commercially available, for example, from Thor as Acticide® and from Evonik Industries as Varisoft®. DDAC is also available from Sigma-Aldrich.

[0070] The disinfectant composition of the present invention comprises three components (i), (ii), and (iii) at predetermined concentrations. The use of the present invention similarly comprises HT61 or a pharmaceutically acceptable salt and / or solvate thereof at predetermined concentrations. A preferred concentration for 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof is about 0.001 to about 0.5 w / v% on a whole basis of the composition. Preferably, the amount of the disinfectant composition is about 0.001 to about 0.4 w / v%, more preferably about 0.001 to about 0.2 w / v%, and particularly preferably about 0.01 to about 0.1 w / v%, for example, 0.001, 0.0025, 0.005, 0.075, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, or 0.5 w / v%.

[0071] In various embodiments, the concentration of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof in the composition of the present invention is about 0.001 to about 0.5 w / v%, preferably about 0.001 to about 0.4 w / v%, and more preferably about 0.001 to about 0.25 w / v%.

[0072] The preferred concentrations of chlorhexidine or its pharmaceutically acceptable salts and / or solvates are, on a whole basis of the disinfectant composition, about 0.001 to about 4 w / v%, preferably 0.001 to about 3 w / v%, more preferably 0.001 to about 2 w / v%, and particularly preferably about 0.05 to about 0.5 w / v%. For example, 0.001, 0.0025, 0.005, 0.0075, 0.01, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 3.0, or 4.0 w / v% of the composition.

[0073] In various embodiments of the present invention, the concentration of chlorhexidine is less than about 2 w / v%, for example, 0.01 to 2 w / v%, preferably 0.01 to 1.5 w / v%, and more preferably 0.01 to 1.0 w / v%.

[0074] The w / v percent (w / v%) of chlorhexidine or its pharmaceutically acceptable salts and / or solvates is calculated based on the weight of chlorhexidine or chlorhexidine salts in the composition. For example, "0.1 w / v% chlorhexidine digluconate" means that the composition contains 0.1% chlorhexidine digluconate, based on the weight of the salt and the total volume of the composition.

[0075] The preferred concentration of dialkyldimethylammonium chloride (e.g., DDAC) is about 0.001 to about 2 w / v%, preferably about 0.001 to 1 w / v%, and more preferably about 0.01 to 0.7 w / v%, based on the entire disinfectant composition. For example, the w / v% of the composition is 0.001, 0.0025, 0.005, 0.0075, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.25, 1.5, and 2.0.

[0076] In one embodiment, the disinfectant composition comprises about 0.005 to about 0.5 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, about 0.01 w / v% to about 1.0 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and about 0.01 w / v% to about 1.0 w / v% of dialkyldimethylammonium chloride.

[0077] In one embodiment, the disinfectant composition comprises about 0.005 to about 0.5 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, about 0.05 w / v% to about 0.5 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and about 0.01 w / v% to about 1.0 w / v% of dialkyldimethylammonium chloride.

[0078] In one embodiment, the disinfectant composition comprises about 0.005 to about 0.5 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, about 0.1 w / v% to about 0.5 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and about 0.01 w / v% to about 1.0 w / v% of dialkyldimethylammonium chloride.

[0079] In one embodiment, the disinfectant composition comprises about 0.005 to about 0.2 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, about 0.01 w / v% to about 1.0 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and about 0.01 w / v% to about 1.0 w / v% of dialkyldimethylammonium chloride.

[0080] In one embodiment, the disinfectant composition comprises about 0.005 to about 0.2 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, about 0.01 w / v% to about 0.5 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and about 0.01 w / v% to about 1.0 w / v% of dialkyldimethylammonium chloride.

[0081] There are no weight ratios of components (i), (ii), and (iii) in the disinfectant composition of the present invention, as long as each component is included in the concentrations required for disclosure herein. However, in various embodiments, the chlorhexidine component and the DDAC component are included in a weight ratio of about 0.05:1 to about 1:1, preferably about 0.1:1 to about 1:1, and more preferably about 0.1:1 to about 0.7:1. Furthermore, HT61 and chlorhexidine may be included in a weight ratio of about 0.05:1 to about 1:1, preferably about 0.05:1 to about 0.5:1, and more preferably about 0.1:1 to about 0.3:1. Furthermore, the weight ratio of HT61:chlorhexidine:DDAC can be approximately 0.05:1:10 to approximately 0.5:1:1, preferably approximately 0.05:1:8 to approximately 0.5:1:1, and more preferably approximately 0.05:1:7 to approximately 0.3:1:1.

[0082] The disinfectant composition of the present invention is formulated as a single solution in an aqueous solvent. The expression "formulated as a single solution" means that the disinfectant composition does not need to be mixed before use. This can facilitate ease of use and reflects the compatibility of the components in the aqueous solvent. However, this expression does not exclude dilution of the disinfectant composition, such that in various embodiments the composition may be prepared as a concentrate and then diluted to a desired concentration. When prepared as a concentrate, the concentrations of the various components may, of course, be higher than those described above. For example, DDAC, when included in a concentrate, may be present at a concentration of about 0.01 to about 20 w / v%, preferably about 0.05 to about 10 w / v%, and more preferably about 0.1 to about 5 w / v%.

[0083] In one embodiment, the disinfectant composition comprises about 0.005 to about 0.5 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof, about 0.01 w / v% to about 2.0 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof, and about 0.01 w / v% to about 5.0 w / v% of dialkyldimethylammonium chloride.

[0084] The aqueous solvent used in the present invention is not limited and includes any aqueous solvent known in the art. In various embodiments, the disinfectant composition contains at least 50% by weight of water, preferably at least 70% by weight of water, and more preferably at least 90% by weight of water. These wt%s of water can be combined with the concentrations of each component (i), (ii) and / or (iii) as shown above. In various embodiments, the aqueous solvent is water.

[0085] For the reasons stated above, the aqueous disinfectant composition of the present invention may be alcohol-free. Alcohol means an organic compound having a hydroxyl functional group bonded to a saturated carbon atom. In various embodiments, the composition does not contain C1-8 alcohols, such as methanol, ethanol, propanol, butanol, pentanol, hexanol, and their isomers and mixtures. In one or more embodiments, the composition does not contain ethanol, propanol, butanol, or their isomers or mixtures.

[0086] In various embodiments of the present invention, the composition comprises one or more additional skin conditioners or emollients. Non-limiting examples include aloe, vitamin E, vitamin E acetate, vitamin B3, C6-10 alkanediols, cococaprylic acid lactic acid, and urea. The composition may also contain, for example, one or more additional skin conditioners or emollients in an amount of 0.0001 to about 1.0% by weight. In other embodiments, the composition does not contain additional skin conditioners and emollients.

[0087] In various embodiments of the present invention, the composition further comprises a non-aqueous solvent selected from the group of alkanolamines, glycols or glycol ethers, or alcohols, provided that it is miscible with water within a given concentration range, so that the aqueous disinfectant composition can still be formed as a single solution. The non-aqueous solvent may be selected from ethylene glycol, propylene glycol, glycerol, 1,3-butanediol, glycerol, ethylene glycol methyl ether, ethylene glycol ethyl ether, ethylene glycol propyl ether, ethylene glycol mono-n-butyl ether, diethylene glycol methyl ether, diethylene glycol ethyl ether, propylene glycol methyl, ethyl or propyl ether, dipropylene glycol monomethyl or ethyl ether, diisopropylene glycol monomethyl or ethyl ether, propylene glycol t-butyl ether, and mixtures thereof. In various embodiments of the present invention, the non-aqueous solvent may be selected from ethylene glycol methyl ether, ethylene glycol ethyl ether, ethylene glycol propyl ether, ethylene glycol mono-n-butyl ether, diethylene glycol methyl ether, diethylene glycol ethyl ether, propylene glycol methyl, ethyl or propyl ether, dipropylene glycol monomethyl or ethyl ether, diisopropylene glycol monomethyl or ethyl ether, propylene glycol t-butyl ether, and mixtures thereof. In various embodiments, the non-aqueous solvent includes glycerol. If present, the non-aqueous solvent is used in an amount of about 0.5 to about 15% by weight, preferably less than about 9% by weight, for example, about 0.5% to 9% by weight, more preferably less than about 5% by weight, for example, about 0.5% to about 5% by weight. In various embodiments, the disinfectant composition does not contain the non-aqueous solvent.

[0088] In various embodiments, the aqueous disinfectant composition of the present invention may be contained in a detergent, and the detergent or disinfectant composition itself may further contain one or more components commonly used in detergents, selected from the group consisting of fragrances, dyes, preservatives, surfactants, pH adjusters, etc. The disinfectant composition may be formulated, for example, as a concentrated solution and then diluted with water to prepare a detergent. The detergent typically contains components (i), (ii), and (iii) in the required concentration range and is formulated as a single solution in an aqueous solvent, and can therefore be considered as the disinfectant composition according to the present invention.

[0089] Dialkyldimethylammonium chloride, which is a quaternary ammonium salt, is preferably a cationic surfactant. Furthermore, various embodiments include additional surfactants, preferably nonionic surfactants, in the composition or detergent. Nonionic surfactants can be selected from the group consisting of polyalkoxylates, alkoxylated fatty alcohols, alkoxylated fatty acids, alkoxylated alkylphenols, and block copolymers of ethylene oxide and propylene oxide. In other embodiments, the composition or detergent does not contain further surfactants.

[0090] The fragrance composition may typically contain up to 2% by weight, preferably 0.01 to 1% by weight, and more preferably 0.02 to 0.75% by weight. The fragrance composition may contain individual aromatic compounds or mixtures thereof. Suitable compounds are known in the art and may include esters, ethers, aldehydes, ketones, alcohols, and hydrocarbons. The fragrance composition may also contain natural aromatic compounds, such as those obtained from plant sources.

[0091] All known acids or bases can be used as pH adjusters, and in this way, they can be used to adjust the pH in either direction (i.e., to make the composition more acidic or more basic). To improve the aesthetic appearance of the compositions, they can be colored using suitable dyes. Preferred dyes have high storage stability and are not sensitive to other components of the composition or to light.

[0092] In one embodiment of the present invention, the disinfectant composition further comprises a β-lactam antimicrobial agent as described in the applicant's patent application WO2012 / 017215. β-lactam antimicrobial agents suitable for use in the present invention include the following compounds:

[0093] (i) Penicillins, for example, (I) Benzylpenicillin, procaine benzylpenicillin, phenoxymethylpenicillin, methicillin, propicillin, epicillin, cyclacillin, hetacillin, 6-aminopenicillaneic acid, penicillic acid, penicillane sulfone (sulbactam), penicillin G, penicillin V, fenticillin, phenoxymethylpenicillic acid, azurocillin, carbenicillin, cloxacillin, D-(-)-penicillamine, dicloxacillin, naphicillin and oxacillin, (II) Penicillinase-resistant penicillins (e.g., flucloxacillin), (III) Broad-spectrum penicillins (e.g., ampicillin, amoxicillin, methampicillin and cavanpicillin), (IV) Anti-Pseudomonas penicillins (e.g., carboxypenicillins such as ticarcillin or ureidopenicillins such as piperacillin), (V) Mesilinum (e.g., Pivmecilinum), or (VI) Any combination of two or more drugs mentioned in (I) to (V) above, or any combination of any drug mentioned in (I) to (V) above with a β-lactamase inhibitor such as tazobactam or, in particular, clavulanic acid (which may be in the form of a metal salt, for example, a salt with an alkali metal such as sodium or, in particular, potassium); (ii) Cefaclor, cefadroxil, cephalexin, cefcapene, cefcapene pivoxil, cefdinir, cefditoren, cefditoren pivoxil, cefixime, cefotaxime, cefpirome, cefpodoxime, cefpodoxime proxetil, cefprodil, ceffradil, ceftazidime, cefteram, cefteram pivoxil, ceftriaxone, cefuroxime, Cephalosporins such as phloxime axetil, cephaloridine, cefacetril, cephamandol, cephaloglysin, ceftobiprole, PPI-0903 (TAK-599), 7-aminocephalosporanic acid, 7-aminodes-acetoxycephalosporanic acid, cephamandol, cefazolin, cefmetazole, cefoperazone, cefsulozin, cephalosporin C zinc salt, cephalothin, cefapillin, and others; and (iii) monobactams (e.g., aztreonam), carbapenems (e.g., imipenem (combined with a renal enzyme inhibitor such as cilastatin, if necessary), meropenem, ertapenem, doripenem (S-4661 and RO4908463 (CS-023)), penems (e.g., faropenem) and other beta-lactams such as 1-oxa-β-lactams (e.g., moxalactam).

[0094] Methods for producing disinfectant compositions are known in the art. Such methods may include, for example, combining components and adding them to an aqueous solvent (e.g., water).

[0095] In various embodiments, the disinfectant compositions of the present invention are suitable for topical use. This means that the compositions are suitable for direct application to surfaces such as the skin of a human or animal body, and / or other surfaces such as hair and nails. Accordingly, the disinfectant compositions can be in the form of skin cleansers, skin disinfectants, skin protectants, wipes, ointments, gels, etc. A wide variety of media can be used to deliver the compositions, for example, pads, bandages, patches, sticks, aerosol dispersers, pump sprays, trigger sprays, canisters, foam pumps, wipes, etc. Accordingly, in various embodiments, the present invention provides consumer products comprising cleansing compositions, the product of which includes disinfectant sprays, hand sanitizer solutions or gels, antibacterial wipes or pap.

[0096] In such embodiments, the disinfectant composition may include components typically included for these uses. The composition may include, for example, thickeners (e.g., hydroxymethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, or carbomer); or gelling agents (e.g., polyoxyethylene-polyoxypropylene copolymer); or preservatives (e.g., benzyl alcohol, benzalkonium chloride, chlorhexidine, chlorbutol, benzoic acid compounds, potassium sorbate, or EDTA, or salts thereof).

[0097] The disinfectant composition may also be suitable for use on non-mammalian surfaces, i.e., surfaces other than the human body. For example, this composition can be used to disinfect various surfaces in homes and buildings, as well as building materials and furniture. Furthermore, the disinfectant composition may be for clinical use and / or may be used to sterilize not only surfaces but also objects, such objects may include medical devices and other medical equipment.

[0098] Accordingly, the present invention relates to the use of disinfectant compositions or cleaning agents according to the present invention for cleaning and / or disinfecting articles or surfaces, and to methods for disinfecting surfaces or articles. Preferably, the surface is a hard surface, and the use of the disinfectant composition or cleaning agent reduces the number of microorganisms on the article or surface treated thereby. Contact or application of the composition or cleaning agent to the article or surface can be carried out by any suitable method, for example, by pouring, spraying, or otherwise wetting the article or surface with the composition or agent of the present invention. The composition may also be applied, for example, by rubbing the article / surface with a brush, sponge, or cloth wet with the composition.

[0099] Embodiments of the disinfectant composition include those described in the examples below, and the following.

[0100] [Table 1]

[0101] Next, the present disclosure will be illustrated by reference to the following non-limiting embodiments. [Examples]

[0102] Example 1: HT61 as a skin emollient To support the use of low concentrations of HT61 as a emollient in aqueous disinfectant compositions, the surface tension, contact angle, and hydrophilic-lipophilic balance (HLB) of this compound were measured.

[0103] Sample preparation: A 0.03 w / w% solution was required for both contact angle and surface tension measurements. This solution was prepared by adding 0.075 g of HT61 solid (obtained according to the method described in WO2007 / 054693A1 above) to 250 mL of desalted water. Since some solid remained in the solution, analysis was performed using UV-Vis spectral analysis. This analysis revealed two large absorption peaks in the 350–400 nm region. These peaks were attributed to the compound in question, leading to the conclusion that HT61 had dissolved and saturated the solution.

[0104] Approximately 100 mL of the test sample was taken from a volumetric flask using the tilting method and used to measure surface tension and contact angle.

[0105] Methods: The surface tension of the samples was measured using a DataPhysics DCAT 9 tensile meter and the Wilhelmie plate method. Measurements were performed three times, and the plates were cleaned between each measurement.

[0106] The contact angle was measured on the surface of Parafilm. A Parafilm sample was wrapped around a glass slide and the protective film was removed. A small droplet (e.g., 2 μL) of the test solution (sample) was placed on the surface, and the contact angle of the solution to the Parafilm was measured. The droplet's shape was measured as a function of time using DataPhysics OCA 35. Each solution was measured three times. The contact angle was measured 2 seconds, 12 seconds, and 30 seconds after the droplet first touched the surface. For reference, the contact angle of demineralized water was also measured.

[0107] HLB values ​​were obtained using Griffin's mathematical method (Griffin, WC, Calculation of HLB Values ​​of Non-Ionic Surfactants, Journal of the Society of Cosmetic Chemists, 1954, 5(4), 249-56). HLB = 20 × (M h / M) In the formula, M h The molecular weight of the hydrophilic group is (44 gmol)-1 ) and M is the total molecular weight of the molecule (380 gmol). -1 )

[0108] The coefficient 20 is a multiplier. Therefore, values ​​between 1 and 20 can generally be obtained.

[0109] result:

[0110] [Table 2]

[0111] The HLB value of HT61 using Griffin's mathematical method is 2.3.

[0112] Conclusion: Assuming the HT61 solution is saturated, there is a significant difference between the surface tension of desalinated water and the surface tension of the HT61 solution (55.7 vs. 72.5 mN / m). The surface tension of an emollient is an elastic-like force between the emollient and the air, and it strongly influences the wetting properties of the emollient on the surface. Surface tension, along with viscosity, correlates with ductility.

[0113] The contact angle of the HT61 solution was lower than that of demineralized water, at 96 to 110 degrees relative to water over 30 seconds. To further determine the ductility properties, the contact angle and ductility value can be measured. When liquid molecules are strongly attracted to solid molecules, the droplet spreads completely on the solid surface, corresponding to a contact angle of 0°. This is often observed with respect to the angle of water on exposed metal or ceramic surfaces. Finally, the HLB value for HT61 is 2.3. Hydrophilic-lipophilic balance (HLB) is the balance of size and strength between the hydrophilic and lipophilic parts of a surfactant molecule. An HLB value of 1 indicates a lipophilic compound, while a compound with an HLB value of 20 has a highly hydrophilic portion.

[0114] In summary, the surface tension, contact angle, and HLB value of HT61 support its emollient properties, and therefore support the use of this compound in the present invention.

[0115] Example 2: Preparation of disinfectant composition The following disinfectant compositions were prepared. Unless otherwise noted, all values ​​are in w / v%.

[0116] [Table 3]

[0117] Sample 1 was prepared as a concentrated solution and diluted 1:10 to make it ready for immediate use. All other samples were prepared in the ready-to-use form.

[0118] Example 3: Activity Test The sample prepared in Example 2 was subjected to an activity test.

[0119] First, two screening tests were performed on each sample against poliovirus and vacciniavirus according to the BS EN 14476 protocol. Virucidal activity was observed.

[0120] The following sample was also subjected to activity testing according to the BS EN 14476 protocol. This sample is referred to as Blend G.

[0121] [Table 4]

[0122] Blend G is particularly useful as a "rapid hand-washing solution." The solvent is a mixture of non-aqueous and aqueous components, specifically 2.50% glycerol and 96.52% water.

[0123] Standard method BS EN 14476 describes test methods and minimum requirements for the virucidal activity of chemical disinfectants and bactericides that form homogeneous and physically stable formulations when diluted with hard water or for immediate-use products that are not diluted with water at the time of application. Because some degree of dilution always occurs when adding test organisms and interfering substances, products can only be tested at 80% concentration. This European standard applies to products used in the medical field in the areas of hygienic hand rubbing, hygienic hand washing, disinfection of instruments by immersion, surface disinfection by wiping, spraying, immersion, and other means, and disinfection of textile products.

[0124] This European standard also applies to areas and situations where disinfection is medically mandated. Such instructions may arise in patient care, for example, in hospitals, community healthcare facilities, dental clinics, or clinics in schools, kindergartens, and nursing homes, and may also occur in workplaces and homes. This may also include services that supply products directly to patients, such as laundry rooms and kitchens.

[0125] Overview of the testing method (mandatory testing conditions) For products that are diluted before use, dilute the test sample with synthetic hard water; for immediate use products, add water to the test virus suspension in the interfering substance solution. Maintain this mixture at one of the temperatures and contact times specified in the standard. After this contact time, take a small sample and immediately suppress the viricidal activity of this portion by a validated method (dilution of the sample in ice-cold cell maintenance medium). Transfer the diluted solution to a cell culture unit using a monolayer or cell suspension. Perform infectivity testing by either a plaque test or a quantum test. After incubation, calculate the infectivity titer according to the Spearman-Carver method or by plaque counting. The reduction in viral infectivity is calculated from the difference in 1g virus titer before (viral control) and after treatment with the product.

[0126] Selection Criteria When tested using the method described above, this product should show a reduction of at least 4log10 against the test virus. This test is considered valid only if all control requirements are met.

[0127] The test data is as follows:

[0128] [Table 5]

[0129] Blend G achieved a 4-log reduction against vaccinia virus, demonstrating virucidal activity against vaccinia virus according to the BS EN 14476 protocol.

[0130] Simultaneously with the screening test, skin patch tests were performed on each of the five samples in Example 2. No dermatological problems were identified in these patch tests.

[0131] At least one sample was further tested for feline coronavirus according to the BS EN 14476 protocol and for antibacterial activity according to the BS EN 1500 protocol. Viral and antibacterial activity was observed. Finally, at least one sample was tested according to the complete BS EN 17126 protocol (spore-killing) including C. difficile. Spore-killing activity was confirmed.

[0132] Further antibacterial activity testing was performed on Blend G according to the BS EN 1500 protocol. The experimental conditions were as described in this standard. That is, Neutralizing agent: BU broth Bacterial strain: Escherichia coli (E. coli) K12 NCTC 10538 Product dilution: Undiluted (as provided) Application of the test product: Apply 4 mL to dry hands. Rub hands together for 60 seconds. Incubation temperature: 36℃±1℃.

[0133] Blend G was not inferior to the standard product (hand rubbing agent containing 60% propane-2-ol) and therefore met the requirements of EN 1500:2013.

[0134] Example 4 - Further Certification Additional blends were prepared and tested as follows.

[0135] Blend A: Concentrated disinfectant cleaning solution Chlorhexidine digluconate (Chlorhex): 1.00% Didecyldimethylammonium chloride (DDAC): 1.40% HT61: 0.10% Other additives (e.g., nonionic surfactants): 7.35%

[0136] Blend B: Immediate-use disinfectant cleaner Chlorhex: 0.10% DDAC: 0.14% HT61: 0.01% Other additives (e.g., nonionic surfactants): 0.74% Solvent: Remainder

[0137] Blend C: Disinfectant cleaning agent (for clinical use) Chlorhex: 0.50% DDAC: 0.18% HT61: 0.05% Other additives (e.g., nonionic surfactants): 0.74% Solvent: Remainder

[0138] Blend D: Medical device disinfectant cleaner Chlorhex: 0.50% DDAC: 0.70% HT61: 0.05% Other additives (e.g., nonionic surfactants): 3.68% Remaining: Solvent

[0139] Blend E: Static electricity disinfectant solution Chlorhex: 0.25% DDAC: 0.14% HT61: 0.05% Other additives (e.g., nonionic surfactants): 0.37% Solvent: Remainder

[0140] Blend F: Hand sanitizer Chlorhex: 0.25% DDAC: 0.18% HT61: 0.05% Other additives (e.g., nonionic surfactants): 0.35% Solvent: Remainder

[0141] Blends A and B A completely equivalent blend, except for the absence of HT61, has already received certification under BS EN 1276, 13697, 16615, 1560, 13624, and 13727. Therefore, a blend containing HT61 should also be able to obtain these certifications. Furthermore, the presence of HT61 provides emollient properties, as described and supported by Example 1 above.

[0142] Blend C This blend is certified to BS EN 1500 and 14476. Due to the increased content of Chlorhex and DDAC, it can be assumed that it meets the requirements of the above EN standards for blends A and B.

[0143] Blend D This blend has been empirically tested according to the methods of ISO CEN ISO / TS15883-5:2005 Disinfectants for washing machines - Part 5. This test demonstrated complete removal of biofilm within a 10-second exposure time.

[0144] Blend E Feedback from ATP testing of this blend in 20 individual facilities demonstrated excellent disinfecting efficacy.

[0145] Blend F In addition to the above certifications for blends A and B, this blend is expected to also meet the requirements of BS EN 1500 and 14476.

[0146] Blend G This blend (see Example 3) satisfies the requirements of BS EN 1500 and 14,476. Because of the increased content of chlorhexidine and DDAC, it can be assumed that it satisfies the requirements of the above EN standards for blends A and B.

[0147] Various modifications and alterations to the present invention will be apparent to those skilled in the art, without departing from the scope and spirit of the invention. While the present invention has been described above in relation to specific preferred embodiments, it should be understood that the claimed invention should not be unduly limited to such specific embodiments. Indeed, various modifications of the described forms for carrying out the invention, which would be apparent to those skilled in the chemistry or related art, are intended to be included within the scope of the appended claims.

Claims

1. (i) 0.001 w / v% to 0.1 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof; (ii) 0.001 w / v% to 4 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof; and (iii) 0.001 w / v% to 2 w / v% dialkyldimethylammonium chloride (the alkyl group having 8 or more carbon atoms) A disinfectant composition containing, A disinfectant composition formulated as a single solution in an aqueous solvent.

2. The disinfectant composition according to claim 1, wherein the composition comprises 0.01 w / v% to 0.1 w / v% of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and / or solvate thereof.

3. The disinfectant composition according to claim 1 or claim 2, wherein the composition comprises 0.001 w / v% to 2 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof.

4. The disinfectant composition according to claim 3, wherein the composition comprises 0.05 w / v% to 0.5 w / v% of chlorhexidine or a pharmaceutically acceptable salt and / or solvate thereof.

5. The disinfectant composition according to any one of claims 1 to 4, wherein the dialkyldimethylammonium chloride is selected from dioctyldimethylammonium chloride, octyldecyldimethylammonium chloride, and didecyldimethylammonium chloride.

6. The disinfectant composition according to claim 5, wherein the composition comprises 0.001 w / v% to 1 w / v% didecyldimethylammonium chloride.

7. The disinfectant composition according to any one of claims 1 to 6, wherein the composition is biodegradable.

8. The disinfectant composition according to any one of claims 1 to 7, wherein the aqueous solvent is water.

9. The disinfectant composition according to any one of claims 1 to 8, wherein the composition has antiviral activity as measured by BS EN 14476.

10. The disinfectant composition according to claim 9, wherein the virucidal activity of the composition is against picornavirus, poxvirus, coronavirus, or a combination thereof.

11. The disinfectant composition according to any one of claims 1 to 10, wherein the composition has antibacterial activity as measured by BS EN 1500.

12. A disinfectant composition according to any one of claims 1 to 11, which is a spore-killing disinfectant composition.

13. The disinfectant composition according to claim 12, wherein the composition has spore-killing activity as measured by BS EN 17126.

14. A consumer product comprising the disinfectant composition according to any one of claims 1 to 13.

15. The consumer product according to claim 14, wherein the product comprises at least one of a disinfectant spray, a hand sanitizer solution or gel, a disinfectant wipe or a disinfectant patch.

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