CN101453889A - Composition and method for controlling the transmission of noroviruses - Google Patents

Abstract

Antimicrobial compositions having a rapid effectiveness against noroviruses and against bacteria are disclosed. The antimicrobial compositions contain a disinfecting alcohol, an organic acid, and water, wherein the composition has a pH of about 5 or less and the nonvolatile components of the composition are capable of forming a barrier film or layer on a treated surface.

Description

Be used to control composition and the method that the class norwalk virus infects

The cross reference of related application

[0001] the application requires the U.S. Provisional Patent Application No.60/802 of submission on May 24th, 2006, the U.S. Provisional Patent Application No.60/811 that on June 6th, 911 and 2006 submitted to, 354 rights and interests.

Technical field

[0002] the present invention relates to have the antimicrobial compositions (replace in full) of quick antivirus action.More particularly, the present invention relates to antimicrobial compositions, such as hand-cleaning liquid (handsanitizer) composition, it comprises ethanol for disinfection, organic acid and optional active antimicrobial agent, and it is effective in control class norwalk virus (noroviruses).The pH that described composition has is about 5 or littler, makes the norwalk virus population reduce the class C in fact in one minute.In certain embodiments, composition provides organic acid barrier film or film to give this surface lasting antiviral activity on surface treated.

Background technology

[0003] every day, the influence of the various microorganisms that human health is all met with.Especially, contact with various microorganisms in the environment and can cause mammal ill, may suffer from serious disease.For example, microbial contamination can cause multiple disease, include, but are not limited to food poisoning, streptococcal infection, anthrax (malignant pustule), the ringworm of the foot, cold sore, conjunctivitis (" blood-shot eye illness "), Coxsackie virus (hand-feet-mouth disease), croup, diphtheria (cutaneous diphtheria), ebolic Hemorrhagic fever and impetigo.

[0004] washs body part (for example washing one's hands) and crust (for example table top and sink) as everyone knows and can reduce the microbial population that comprises pathogene significantly.Therefore, cleaning skin and other animate and inanimate surface is first road defence of removing such pathogene from these surfaces to reduce microbial population, itself thereby the danger of infection is minimized.

[0005] virus is the mainly relevant pathogene of a class.Virus infections is the most important reason of human morbidity, estimate in developed country all human diseasess 60% or to surpass 60% outbreak be to be caused by virus infections.In addition, in fact virus infect natural every kind of microorganism, all mammals, comprises in the mankind, pet, domestic animal and the zoo sample all having high viral infection rate.

[0006] virus demonstrates structure and life cycle diversity widely.At Fundamental Virology, the 4th edition, Eds.Knipe ﹠amp; Howley, LippincottWilliams ﹠amp; Wilkins, Philadelphia, PA has discussed virus family, their detailed description of mode of structure, life cycle and virus infections in 2001.

[0007] in simple terms, virion is intrinsic obligate parasite, and the enough information of genetic material between can transfer sell and coding that has been evolved into is to protect their self-reproductions.In the most basic form, virus is made up of the little nucleotide fragments that wraps in the single protein shell.Major different is enveloped virus and nonenveloped virus between virus,, comprises or do not comprise those of lipid-bimolecular tunic respectively that is.

[0008] virus is only bred in living cells.The major obstacle that virus is run into is to enter cell, and cell is subjected to thickness to be equivalent to the membrane protective of viral size.For penetration cell, virus at first must be attached to cell surface.Virus depends on its ability attached to the specific cells surface to a great extent for the specificity of certain cell type.Lasting contact is very important for the virus infections host cell, and virus and the interactional ability of cell surface are a kind of character of virus and host cell.Virus and the complete virion of the fusion of host cell membrane permission, perhaps in some cases only its infectious nucleic acid enter cell.Therefore, in order to control virus infections, the virus of killing contact skin apace is very important, and this can provide lasting antiviral activity with the control virus infections to skin or abiotic surface in theory.

[0009] for example, known rhinovirus, influenza virus and adenovirus can cause respiratory tract infection.Rhinovirus is the member of pico+ribonucleic acid+virus family, and this family is a family that does not have adventitia " naked virus ".The human rhinovirus so calls because they are particularly suitable for the nasopharynx zone, and they are adult and the topmost pathogene of children's common cold.102 kinds of rhinovirus serotypes of formal existence.From most of picornavirus acid labile that the human respiratory system separates, this lability becomes rhinoviral definition feature.

[0010] rhinovirus infection is to be spread by the respiratory secretions of interpersonal directly contact viral pollution.Typically, this contact is the form that health contacts with contaminated surface, rather than sucks via airborne virion.

[0011] rhinovirus can survive a few hours on environmental surfaces in the initial back of polluting, if the new finger that pollutes wipes one's eyes subsequently or contacts schneiderian membrane, then infects the environmental surfaces and finger contact transmission that contact with finger and pollute by finger easily.Therefore, the viral pollutant of skin and environmental surfaces should minimumly be given the danger of general population to reduce infectious disease transmission.

[0012] some gastrointestinal infection diseases are also caused by virus.For example, in the U.S., estimate that the class norwalk virus causes 2,300 ten thousand acute gastroenteritis cases every year, it is the main cause of gastroenteritis in the U.S..In virus, it is reported that to have only common cold more general than viral gastroenteritis (class norwalk virus).The class norwalk virus causes nausea, vomits (sometimes with diarrhoea) and gastrospasm.This infection is typically spread by interpersonal direct contact.

[0013] class norwalk virus (class norwalk virus belong to, Caliciviridae family) is a kind of relevant, single stranded RNA, nonenveloped virus that causes human acute gastroenteritis.Recently, the class norwalk virus goes through as the formal generic name that is described as " C (Norwalk)-sample virus " virus group (NLV) temporarily.Because their virus family title, this papova also are called as calicivirus (calciviruses), and because their morphological feature, they are called as little round shape structure virus or SRSV.Norwalk virus is the prototype virus that the class norwalk virus of Caliciviridae family belongs to.Another genus that can cause the calicivirus family of human gastrointestinal inflammation is Sapovirus, is described as " Sapporo-sample virus " (SLV) before, is sometimes referred to as traditional or typical calicivirus

[0014] the class norwalk virus is divided into five kinds of different genomes (GI, GII, GIII, GIV and GV) by genetics, and it can further be divided into different genotype or genotype.For example, genome II, the most general human genome comprises 17 genotype at present.Genome I, II and IV infect human.In history, the place name (for example Norwalk, Hawaii, Snow Mountain, Southamptom or Bristol) of class norwalk virus wherein to occur spreading, but the digital sort system has been accepted in the whole world recently.This categorizing system is based on Roman number and gives genome (genogroup) numbering and give genotype (genotype) numbering with numeral.For example, genome II class norwalk virus, Lordsdale virus is the member of genotype 4, therefore, is categorized as GII.4 class norwalk virus.GII.4 virus is that the adult is broken out gastroenteritis and common pandemic main cause.

[0015] the class norwalk virus has very high contagiosity, can easily spread between men.Ight soil (dung urine) vomitus all is infectious.In theory, few inoculum to 10 virions can enough infect body one by one.The class norwalk virus is mainly propagated by ight soil-mouth approach, by polluting of draining food or water or spread by interpersonal directly the contact.Environment and the pollutant that carries disease germs also can serve as source of infection.

[0016] people can infect the class norwalk viruses by several approach, comprises the food that feed is polluted by the class norwalk virus or drinks by the liquid of its pollution; Contact is by class norwalk virus surfaces contaminated or object, and the hand with them is placed in their mouth then; Perhaps with infect and demonstrate symptom other people directly contact (for example, when looking after certain ill man-hour, or during) with ill someone shared food or tableware.Confirmed several circulation ways, for example, then secondly be transmitted to the kinsfolk contactee between men at first at the food transmission in dining room at class norwalk virus gastroenteritis burst period.There is not evidence to show that it is to take place by respiratory system that the class norwalk virus infects.

It is reported [0017], live in the Inst environment that for example among the elderly in sanatorium, class norwalk virus disease postpones outburst.In some cases, described outburst is owing to the carrier (for example food or water) that is exposed to manure contamination causes at first.Then, outburst is by the interpersonal its spread in china between the resident.This spreads and is subjected to the living area sealing and causes that by incontinence, active or spiritual warning the reduction of personal hygiene level promotes.Because under medical conditions, the disease among these the elderlys may be serious or fatal.

[0018] passenger on tourism passenger steamer and the naval vessels and crew often are subjected to the influence of gastroenteritis outburst.The tourism passenger steamer often rests in the country of health level deficiency, thereby has increased and carry the dangerous of the water of going on board and food pollution or have the active passenger who infects to go on board.After passenger or crew had the class norwalk virus aboard ship, airtight living area had enlarged the chance of interpersonal propagation on the ship.And during cruising continuously, every several days or passenger several Zhou Xin and susceptible arrive the chance that lasting propagation is provided on the affected tourism passenger steamer.Reported that class norwalk virus outburst continuity surpasses continuous the cruising of ten secondaries.

[0019] present, do not have antiviral drugs antagonism class norwalk virus effective, and do not have the standard method of infection prevention.Can not infect with antibiotic therapy class norwalk virus.The class norwalk virus also has relative repellence to environment challenge.The class norwalk virus can freezing, survive under up to 60 ℃ temperature, and even in shellfish, still join after the boiling with disease association.And the class norwalk virus can be survived under the chlorine of 10ppm at the most, and it has obviously surpassed the level of chlorine that is present in usually in the public water system.Although these features are arranged, simple relatively method such as handle cold food rightly, frequently the sick leave (paid sickleave) of washing one's hands and retain one's original salary can reduce the propagation of class norwalk virus in fact.

[0020] although end the difficulty that has of interpersonal propagation, frequently washing one's hands with soap and water is a kind of precautionary approach.The method of recommending is with being coated with the powerful together wiping all surface of hand lathery at least 10 seconds, and abundant flushing hand under current is then being gone to toilet or more behind the changing babies' napkin and on the feed or before the manufacturing food especially.Because environmental surfaces participates in the propagation of enterovirus, should wash the surface of having made dirty with suitable antimicrobial agents in order product (for example 10% household bleach solution).

[0021] normal domestic use phenol/pure disinfectant is effectively to the environmental surfaces of sterilization pollution, but lacks lasting viricidal activity.It is very effective for the finger of sterilization pollution to wash one's hands, but also lacks lasting activity.The explanation of these shortcomings need have the virucidal compositions of lasting antiviral improvement such as class norwalk virus activity.

[0022] the antimicrobial personal care composition is known in the art.Especially, its antimicrobial cleaning compositions that typically is used for washed skin and destroys the bacterium on skin, particularly hand, arm and the face be present in the user is well-known commercially available prod.

[0023] bactericidal composition is used for for example health care industry, food service industry, meat industry and individual consumer's private sector.The extensive use of bactericidal composition has shown that consumer thinks that the bacterial population of control skin is very important.The example of bactericidal composition provides in fact and reduces bacterial population fast and do not have the adverse side effect relevant with toxicity and skin irritatin with wide spectrum ground.Such bactericidal composition is disclosed in United States Patent(USP) Nos. 6,107, in 261 and 6,136,771, is incorporated by reference this paper.

The antibiotic personal care composition of [0024] one class is a hand detergent.This based composition is mainly by medical worker be used for sterilizing hand and finger.Hand detergent be applied to obliterating at hand and finger, said composition is evaporated from skin.

[0025] hand detergent comprises a high proportion of alcohol such as ethanol.To exist at high proportion, alcohol itself also plays disinfectant to alcohol in said composition.In addition, pure rapid evaporation has been avoided the skin that wiping or washing are handled with hand detergent.Yet, comprise a high proportion of alcohol, promptly about 40% of composition or the hand detergent of higher weight have the tendency of dry and chafe.

[0026] the antibiotic cleaning composition typically is included in antimicrobial activity, surfactant and the various other components in water and/or the alcohol carrier, for example dyestuff, aromatic, pH regulator agent, thickener, skin conditioning agent etc.Some different types of antibacterial agents in the antibiotic cleaning composition, have been used.The example of antibacterial agent comprises the phenol and the phenolic compound of biguanides (for example Chlorhexidine digluconate), diphenyl compounds, phenmethylol, three halogen diphenylurea, quaternary ammonium compound, ethoxylation, such as the phenolic compound of halogen-replacement such as PCMX (promptly to chloro-meta-xylene phenol) and triclosan (promptly 2,4,4 '-three chloro-2 '-dihydroxy diphenyl ether).Demonstrate from low paramount antibacterial activity widely based on the antimicrobial compositions of such antibacterial agent, depend on the microorganism that to control and concrete bactericidal composition.

[0027] the most commercial bactericidal composition provides usually and is low to moderate medium antibacterial activity, and report does not have antiviral activity.Antibacterial activity comprises that with anti-broad-spectrum micro-organisms Gram-positive and gram-negative micro-organism estimate.The logarithm of the bacterial population that bactericidal composition provides (log) reduces or percentage reduces all relevant with antibacterial activity.For the specific time of contact that is generally 15 seconds to 5 minute, it is preferred that log reduces 1-3, and it is most preferred that log reduces 3-5, and log to reduce less than 1 be that preference degree is minimum.Therefore, highly preferred bactericidal composition demonstrates anti-broad-spectrum micro-organisms log minimizing 3-5 in short time of contact.

[0028] yet, virus control faces more difficult problem.By reducing bacterial population fully, just risk of bacterial infections can be reduced to acceptable level.Therefore, antibiotic apace killing expected.Yet for virus, not only expectation is killed it fast, and needs total antiviral activity.This some difference is to be not enough to reduce infection because only reduce virus population.For example, under the situation of class norwalk virus, about 10 virions can cause infection.In theory, single virus just can cause infection.Therefore, for effective antiviral Cleasing compositions, require or at least expectation basically all with lasting antiviral activity.

[0029] WO 98/01110 discloses the composition that comprises triclosan, surfactant, solvent, chelating agent, thickener, buffer and water.The surfactant that WO 98/01110 relates to by using reduction reduces skin irritatin.

[0030] U.S. Patent No. 5,635, and 462 disclose the composition of the surfactant that comprises PCMX and selection.Wherein disclosed composition does not contain anion surfactant and non-ionic surface active agent.

[0031] EP 0 505 935 discloses and has comprised the particularly composition of the combination of non-ionic block copolymer surfactant of PCMX and nonionic and anion surfactant.

[0032] WO 95/32705 disclose a kind of can with the combinations-of surfactants of the gentleness of antimicrobial compound such as triclosan combination.

[0033] WO 95/09605 discloses the bactericidal composition that comprises anion surfactant and alkyl poly glucoside surfactant.

[0034] WO 98/55096 discloses the antimicrobial rag with the porous plate that injects bactericidal composition, and described composition comprises active antimicrobial agent, anion surfactant, acid and water, and the pH that wherein said composition has is about 3.0 to about 6.0.

[0035] people such as N.A.Allawala is at J.Amer.Pharm.Assoc.-Sci.Ed., Vol.XLII, and no.5,267-275 page or leaf (1953) has been discussed the antibacterial activity of antimicrobial activity and combinations-of surfactants.

[0036] A.G.Mitchell, J.Pharm.Pharmacol, the 16th volume, 533-537 page or leaf (1964) discloses the composition that comprises PCMX and non-ionic surface active agent that demonstrates antibacterial activity.

[0037] for the hand detergent gel, U.S. Patent No. 5,776,430 disclose a kind of topical anti-microbial cleaning agent that comprises Chlorhexidine and alcohol.Described composition comprises the methylated spirit of about 50% to 60% weight and the Chlorhexidine of about 0.65% to 0.85% weight.Described composition is applied to skin, firmly cleans skin, wash from skin then.

[0038] european patent application 0 604 848 discloses a kind of gel-type hand disinfectant, and it comprises the alcohol of antimicrobial, 40% to 90% weight and polymer and the thickener that gross weight is no more than 3% weight.On hand, and make its evaporation this gel obliterating so that the hand through sterilization to be provided.As in EP 0 604 848, setting forth, think that the quantity of antibacterial agent and character are inessential, because the hand detergent gel comprises the alcohol of the high percentage that antibacterial activity can be provided.Yet,, can reduce to class norwalk virus population 1/3rd just independent alcohol need contact 30 minutes in order to control the class norwalk virus.The composition of the disclosure can not provide anti-class norwalk virus sanitized immediately usually, and can not provide lasting anti-microbial effect.

[0039] common, the hand detergent gel typically comprises the ethanol of (a) at least 60% weight or the combination of lower alcohol, described lower alcohol is such as ethanol and isopropyl alcohol, (b) water, (c) gel polymer, such as crosslinked polyacrylate material and (d) other composition, such as skin conditioning agent, aromatic etc.In washing not or after with soap and water washing, consumer is by using the obliterating of described hand detergent gel this hand detergent gel hand of sterilizing effectively on the surface of hand.The alcohol of at present commercially available hand detergent gel dependence high-load is sterilized and is evaporated, thereby has many shortcomings.Especially, because high-caliber alcohol is applied in the composition, present hand detergent gel has the tendency of dry and chafe.And because the volatility of ethanol, behind application controls class norwalk virus, main active disinfectant can not be retained on the skin enough long-time, and therefore anti-these viral anti-microbial effects can not be provided.

[0040] is lower than 60% time at determining alcohol, thinks that ethanol can not be as bactericide.Therefore, in comprising the composition that is less than 60% alcohol, must exist other Antimicrobe compound that antibacterial activity is provided.Yet, before the disclosure, also do not solve the composition of composition wherein can provide control of microorganisms in such antimicrobial compositions problem.Therefore, for the preparation of the determining alcohol that comprises reduction, selection can provide the antimicrobial of quick anti-microbial effect and lasting antimicrobial benefit to have any problem.

[0041] United States Patent(USP) Nos. 6,107, and 261 and 6,136,771 disclose highly effectively bactericidal composition.These patent disclosures solve the composition of the problem of bacteria on control skin and the crust, but can not control virus.The applicant recognizes does not have list of references that form with single composition is provided, and mode is resisted bacterium highly effectively, controls the solution of class norwalk virus simultaneously.

[0042] United States Patent(USP) Nos. 5,968, and 539; 6,106,851; With 6,113,933 disclose that to have pH be about 3 to about 6 bactericidal composition.Said composition comprises antibacterial agent, anion surfactant and proton donor.

[0043] the also known antiviral composition that discloses energy deactivation or destruction pathogenic virus, described pathogenic virus comprises rhinovirus, rotavirus, influenza virus, parainfluenza virus, Respiratory Syncytial Virus(RSV) and norwalk virus.For example, U.S. Patent No. 4,767,788 disclose the purposes that glutaric acid comes deactivation or break virus.U.S. Patent No. 4,975,217 disclose the composition that comprises organic acid and anion surfactant, and it is mixed with soap or lotion to control virus.U.S. Patent Publication 2002/0098159 discloses the purposes that proton donor reagent and surfactant comprise the antiviral and antibacterial properties of antimicrobial surface activating agent performance.

[0044] U.S. Patent No. 6,034, and 133 disclose a kind of malic acid, citric acid and C of comprising _1-6The hand cleanser that kills the virus of alcohol.U.S. Patent No. 6,294,186 disclose the combination of benzoic acid analog such as the slaine of salicylic acid and selection, and it can resist effectively and comprise rhinoviral virus.U.S. Patent No. 6,436,885 disclose the known antibacterial agent that antibiotic and antiviral properties can be provided and the combination of 2-Pyrrolidone-5-carboxylic acid, and its pH is 2 to 5.5.U.S. Patent No. 6,110,908 disclose a kind of C of comprising _2-3The topical germicide of alcohol, free fatty acid and 2-mercaptopyridine zinc oxide.

[0045] organic acid in personal wash compositions also is disclosed.For example, WO97/46218 and WO 96/06152 are disclosed in the purposes that organic acid in the surfactant matrix or salt, hydrotropic solvent, triclosan and hydric solvent are used for antimicrobial cleansing compositions.These openly do not have antiviral properties.

[0046] people Antimicrobial Agents and Chemotherapy such as Hayden, 26:928-929 (1984) disclose the hand cleanser that has a residual viricidal activity by use and have ended hand to hand and transmit the rhinovirus sexuality and emit.In the rhinovirus of some type of deactivation, the described hand cleanser that comprises 2% glutaric acid is more effective than placebo.Yet this publication discloses the lotion rhinovirus serotype of anti-wide spectrum effectively that contains glutaric acid.

[0047] that use and the paper handkerchief that kills the virus (paper tissues) that comprise citric acid, malic acid and lauryl sodium sulfate is known by the people who infects common cold in design.Yet, people such as Hayden., Journal of Infectious Diseases, 152:493-497 (1985) reported with the mass treatment of killing the virus or untreated paper handkerchief can end the hand and hand propagation of virus.Therefore, unclear advantage may belong to described composition is added in the viricidal paper handkerchief in prevention rhinovirus flu.

[0048], is difficult to obtain effectively effective antimicrobial compositions of antibacterium and virus simultaneously because bacterium and viral fundamental difference and because the character of antimicrobial and the effect of surfactant combating microorganisms agent.For example, some antimicrobials such as the phenol solvability in water is very low, and for example the solvability of triclosan in water is about 5 to 10ppm (per 1,000,000 parts umbers).By in composition, adding the dissolubility that surfactant can increase described antimicrobial.Yet, increase the dissolubility of antimicrobial and therefore the content of antimicrobial in composition will inevitably cause that not necessarily effect increases.

[0049] although there are many antimicrobial cleansing products at present, they can take multiple product shape (for example deodorant soap, hard surface cleaner and surgery disinfectant), such antimicrobial products typically comprises high-caliber alcohol and/or thick surfactant (harsh surfactants), but it may make the dry and chafe tissue of skin histology.Ideally, personal cleansing product is cleaning skin mildly, can cause stimulation hardly, and can not make skin over-drying after frequent the use.

[0050] therefore, need a kind of antimicrobial compositions, it at short notice can anti-highly effectively broad-spectrum micro-organisms, comprises class norwalk virus and gram-positive bacteria and Gram-negative bacteria, wherein said composition preferably can provide lasting antiviral activity, and it is soft to skin.Method of the present invention and antimicrobial compositions provide the composition of the reduction increase of the mildness that shows improvement and virus and bacterial content.

Summary of the invention

[0051] the present invention relates to antimicrobial compositions, its provide fast antibacterial action and fast, and preferred lasting anti-class norwalk virus effect.Be less than in about one minute, said composition provides abundant control class norwalk virus and fully reduces gram-positive bacteria and Gram-negative bacteria.

[0052] more particularly, the present invention relates to antimicrobial compositions, it comprises sterilization alcohol, organic acid, optional active antimicrobial agent, optional gelling agent and water, and the pH that wherein said composition has is about 5 or lower.In preferred embodiments, described composition can provide the organic acid residual layer on surface treated.Composition of the present invention does not preferably need to have a mind to add the clean surface activating agent, such as anion, cation and amphoteric surfactant.Described optional active antimicrobial agent can be for example phenol or the quaternary ammonium antimicrobial.

[0053] therefore, one aspect of the present invention provides a kind of antimicrobial compositions, it is to killing broad spectrum of bacteria, comprise that gram-positive bacteria and Gram-negative bacteria are highly effective such as staphylococcus aureus, Salmonella choleraesuls (S.choleraesuis), Escherichia coli and pneumobacillus (K.pneumoniae), and deactivation simultaneously or the destruction virus harmful to human health.

[0054] another aspect of the present invention provides a kind of liquid anitmicrobial composition, and it comprises:

(a) the about 25% sterilization alcohol to about 95% weight is as C _1-6Alcohol;

(b) the kill the virus organic acid of effective dose;

(c) about 0% active antimicrobial agent to about 5% weight;

(d) 0% gelling agent to about 5% weight is as colloidal state or polymerization gelling agent; With

(e) water; The pH that wherein said composition has is about 5 or littler.

[0055] in embodiment preferred, described composition provides continuous basically organic acid layer or film to give the surperficial lasting antiviral activity of this processing on the surface of handling.In other embodiment preferred, described composition does not contain the surfactant of intentional adding.

[0056] another aspect of the present invention provides a kind of antibiotic and antimicrobial compositions antiviral activity of having, it comprises sterilization alcohol, organic acid, optional active antimicrobial agent and optional gelling agent, and described organic acid is selected from monocarboxylic acid, polycarboxylic acid, has a plurality of carboxyls, phosphate radical, sulfonate radical and/or sulfate radical polymeric acid partly and composition thereof.

[0057] another aspect of the present invention provides a kind of organic acid antimicrobial compositions that comprises, described organic acid independent (substantive) is in skin and/or can not can not transdermal, and/or the washing of tolerance skin, and/or on skin, form continuous basically barrier film.The log P that such organic acid typically has is less than 1, the anti-effectively broad spectrum of bacteria of described composition, and demonstrate the synergistic activity of anti-class norwalk virus.Described lasting antiviral activity is organic acid residual layer or film on the surface of handling due to especially, during its tolerance several times washing and the normal routine work several hrs and do not remove from skin.

[0058] preferred compositions comprises one or more polycarboxylic acids, polymeric acid and gelling agent.These compositions provide the effectively lasting control of class norwalk virus, and demonstrate the synergistic activity of resisting gram-positive bacteria and Gram-negative bacteria.

[0059] another aspect of the present invention provides a kind of antimicrobial compositions, and it demonstrates fully and preferred lasting control to the class norwalk virus, and the pH that has is about 2 to about 5.

[0060] also aspect of the present invention provides a kind of antimicrobial compositions, and it demonstrates, and the log at gram-positive bacteria (being staphylococcus aureus) is reduced by at least 2 after contacting 30 seconds.

[0061] another aspect of the present invention provides a kind of antimicrobial compositions, and its log that demonstrates at contact anti-Gram-negative bacteria (being Escherichia coli) after 30 seconds is reduced by at least 2.5.

[0062] another aspect of the present invention provides a kind of antimicrobial compositions, and its log that demonstrates at contact anti-class norwalk virus (being genome GI, GII and GIV) after 30 seconds is reduced by at least 2.After applying time of contact of 30 seconds, described antimicrobial compositions also preferably provide the log of anti-class norwalk virus be reduced by at least 2 at least about four hours and at least 2 at least about six hours.In certain embodiments, described antimicrobial compositions provides the log of anti-class norwalk virus to reduce about 2 up to about eight hours.

[0063] another aspect of the present invention provides a kind of antimicrobial compositions, its tolerance skin flushing, for example after water flushing three times, at least 50%, at least 60% and preferably at least 70% the nonvolatile element of being used is retained on the surface of processing, and after water flushing 10 times, the described composition of antiviral amount is retained on the skin effectively.

[0064] another aspect of the present invention provides the consumer products based on antimicrobial compositions of the present invention, for example skin cleaner, body spray (body splash), surgical scrub, Wound nursing agent, hand detergent gel, disinfectant, pet shampoo, crust disinfectant, lotion, ointment, cream, swab, wiping agent (wipe) etc.Composition of the present invention can be wash type (rinse-off) product, but is preferably flushing-free type (leave-on) product.Described composition is a sense organ joyful (esthetically pleasing) and non-stimulated to skin.

[0065] a further aspect of the present invention provides the method for class norwalk virus and Gram-positive and/or Gram-negative bacteria population in the animal tissue that a kind of quick control comprises human tissue, it passes through with composition contact tissue of the present invention such as corium time enough, for example about 15 seconds to 5 minutes or longer, for example about one hour to reduce the level of class norwalk virus population level to expectation.A further aspect of the present invention provides a kind of composition of controlling the class norwalk virus enduringly that demonstrates in animal tissue.

[0066] also aspect of the present invention provides a kind of termination class norwalk virus propagates into lived surface, particularly human skin and oral cavity from animate and inanimate surface composition and method.A kind of method and composition that the class norwalk virus is propagated that is used to control is provided especially, it is by after being applied to skin with described composition, and control is present in class norwalk virus and about four hours of the Sustainable Control class norwalk virus on the human skin or realizes above and about at the most 8 hours period effectively.

[0067] these and other new aspect of the present invention and advantage are set forth in the non-limiting detailed description of following preferred embodiment.

Description of drawings

[0068] Fig. 1 a and 1b are applied to the reflection displaing micro picture that the barrier film that is provided at lip-deep nonvolatile element is gone up on the surface for showing with composition of the present invention;

[0069] Fig. 1 c and 1d are applied to the reflection displaing micro picture that does not have the barrier film after go up on the surface from the teeth outwards for showing with reference composition;

[0070] Fig. 2 is for showing through 10 water flushing backs at the bar chart of the log minimizing of feline calicivirus (FelineCalicivirus).

[0071] Fig. 3 a and 3b bar chart for showing that drying reduced at the log of feline calicivirus after the time; With

[0072] Fig. 4 comprises and shows that the composition A that uses embodiment 14 contacts the bar chart that thumb pad (fingerpad) reduces through the log of a period of time class norwalk virus with the comparison commercially available prod.

Embodiment

[0073] personal care product of known introducing active antimicrobial agent for many years.Because introduced antimicrobial personal care product, many products of thinking such of declaring provide anti-microbial properties.For the most effective, antimicrobial compositions should provide the high log of anti-broad-spectrum biological body to reduce in short as far as possible time of contact.In theory, described composition is also with inactivation of viruses.

[0074] as present configuration, most commercial liquid antibiotic soap composition provides the poor crash time to kill effect (marginal time kill efficacy), the i.e. speed of kill bacteria.These compositions can not be controlled virus effectively.

[0075] antimicrobial hand detergent composition does not typically comprise the alcohol of surfactant and dependence high concentration with the control bacterium.Described alcohol evaporation, thereby can not provide the control of class norwalk virus or lasting bacterial control.Alcohol also can make dry skin and chafe.

[0076] most of present products lack anti-Gram-negative bacteria especially such as colibacillary effect, and Escherichia coli are relevant especially with human health.Yet, when when measuring, composition of the present invention has extra high broad-spectrum antiseptic effect by quick kill bacteria (being to kill (time kill) time) (its with kill enduringly different).These products also lack enough antiviral activities, particularly anti-class norwalk virus activity.

[0077] with the alcohol that adds high percentage, promptly to compare greater than the existing composition of the alcohol of 40% weight, antimicrobial compositions of the present invention provides fabulous broad-spectrum antiseptic effect, and improves the antiviral efficacy of anti-class norwalk virus significantly.The basis that this effect is improved is: (a) find sterilization pure and mild organic acid combination, particularly log P less than about 1 organic acid fully (substantially) improve antiviral efficacy and pH that (b) should the surface after described composition is applied to the surface.An important aspect of the present invention is to keep the time of the low pH prolongation of skin so that lasting antiviral activity to be provided.In embodiment preferred, this is to realize by the film that forms continuous basically non-volatile composition component on skin, and it provides organic acid bank (reservoir) to keep low skin pH.

[0078] term " continuous basically film " refer to residue with the nonvolatile element of the composition of barrier film form account for processing surface area at least 50%, at least 60%, at least 70% or at least 80%, preferably at least 85% or at least 90%, more preferably at least 95%." continuous basically " film is showed subsequent discussion in the reflection displaing micro picture of accompanying drawing.Term " continuous basically film " and term " continuous basically layer ", " barrier film " and " barrier film " are synonyms as used herein.

[0079] the pure and mild log P of sterilization less than 1 organic acid synergy with control class norwalk virus.The pure and mild log P that sterilizes be 1 or bigger organic acid synergy to substantially improve antibiotic effect.Log P less than 1 first organic acid and log P for 1 or bigger second organic acid and the combination of sterilization alcohol the collaborative improvement of control class norwalk virus and gram-positive bacteria and Gram-negative bacteria is provided.Another basis that effect is improved is to find active antimicrobial agent, particularly the antimicrobial efficacy of the antimicrobial of phenol may with described composition is applied to the surface after, the speed that this reagent arrives the activation of microorganism position is relevant with the pH on duration and surface.

[0080] a kind of driving force that determines active antimicrobial agent to be transported to the speed of site of action is the difference of chemical potential between described reagent site of action and the outside water.Show that in addition the bactericidal activity of active antimicrobial agent and its thermodynamic activity in foreign minister (external phase) are proportional.Therefore, opposite with concentration for the effect of antimicrobial, thermodynamic activity is an important variable.Following discussion more fully, thermodynamic activity is relevant in the degree of saturation of the continuous aqueous phase of composition with active antimicrobial agent usually.

[0081] solubility limit that has in the aqueous solution of chemical compound lot is called as " saturated concentration ", and it is with temperature change.Be higher than saturated concentration, compound can be settled out from solution.Saturated percentage (percent saturation) is that measured concentration in solution is divided by saturated concentration.By adding compound such as surfactant, the comparable saturated concentration height in water of the concentration of compound in the aqueous solution.Surfactant not only increases the dissolubility of compound at the continuous aqueous phase of composition, and forms micella, and it can make compound solubilising in micella.

[0082] % of active antimicrobial agent in any composition (comprising the composition that contains surfactant) is saturated, can be expressed as in theory:

% is saturated=[C/C _s] * 100%,

Wherein C is the concentration of antimicrobial in the solution of composition, and Cs is this antimicrobial saturated concentration in composition at room temperature.Think that in theory the continuous water of the composition that contains surfactant intends (pseudophase) balance mutually with the micella of described composition, according to distribution law, the kind of any dissolving is such as antimicrobial activities distribution between water and micella are intended mutually continuously further.Therefore, the antimicrobial activating agent is dissolved in the saturated percentage in the composition that contains surfactant, and perhaps thermodynamic activity or relative chemical potential are identical Anywhere in composition relatively.Therefore, " in the composition " of term antimicrobial, " at the water continuous phase of composition " are interchangeable with saturated percentage in " micella at composition is intended mutually ".

[0083] when the difference of the thermodynamic activity of active antimicrobial agent between described composition and target organism is maximum (, the active component that has when described composition is more when " saturated ") obtains maximum antimicrobial efficacy.Second factor that influences antimicrobial acivity is the total amount that is present in obtainable antimicrobial in the described composition, and it can be considered to " threshold dose ".Find that the hypothesis thermodynamic activity equates, activating agent greatly influences the time of the level of the antimicrobial efficacy that obtains expectation in the total amount of the continuous aqueous phase of composition.Therefore, two key factors that influence the antimicrobial efficacy of activating agent in the composition are: (1) its availability, and as by the i.e. total amount of obtainable activating agent in the saturated percentage decision of the continuous aqueous phase of composition and (2) solution of its thermodynamic activity.The time quantum that keep in touch on the surface that the 3rd key factor is described active antimicrobial agent and processing.

[0084] composition in many antimicrobial cleansing compositions is a surfactant, and it plays the effect of solubilizer, cleaning agent and blowing agent.Surfactant influences the saturated percentage of antimicrobial in solution, perhaps more importantly, influences the saturated percentage of described activating agent at the continuous aqueous phase of composition.This effect can illustrate under the situation of antimicrobial in aqueous surfactant solution of poorly water-soluble that wherein said activating agent distributes mutually and between the micella plan phase at water (promptly continuous).Because the dissolubility of antimicrobial in water be very low, such as triclosan, described distribution consumingly to the micella direction move (that is, most triclosan molecules be present in water facing surfaces activating agent micella in).

[0085] ratio of surfactant and active antimicrobial agent directly determines active antimicrobial agent to be present in the amount in the described surfactant micella, and it influences the saturated percentage of described active antimicrobial agent at continuous aqueous phase again.Find when surfactant: when the ratio of active antimicrobial agent increased, micellar phase also increased for the quantity of bioactive molecule, and when described ratio increased, the micella saturated by active antimicrobial agent reduced pro rata.Because the active antimicrobial agent in continuous phase with intend mutually at micella in the activating agent balance, when the degree of saturation of activating agent in micellar phase reduced, the degree of saturation of antimicrobial in continuous phase also reduced.Vice versa.The active antimicrobial agent of solubilising can not realize contacting microorganism immediately in micella is intended mutually, and activating agent can determine the initial antibacterial activity of composition at the saturated percentage of continuous aqueous phase.The activating agent that is present in the surfactant micella serves as the activating agent bank, and when the activating agent of water exhausted, it can fill continuous water again, and helps the antibacterial activity that provides lasting.

[0086] puts it briefly, help to strengthen (drive) antibacterial activity at the thermodynamic activity or the saturated percentage of the active antimicrobial agent of the continuous aqueous phase of composition.Further, duration of keeping on the surface of handling of the total amount of obtainable activating agent and activating agent has determined the final degree of effect.Use therein in the composition of surface active agent solubilization activating agent, the activating agent that is present in the surfactant micella can not obtain antibacterial activity immediately.For such composition, the saturated percentage of activating agent in described composition, perhaps activating agent has determined initial antimicrobial efficacy at the saturated percentage of the continuous aqueous phase of described composition.

[0087] although the verified composition that contains the active antimicrobial agent of high saturated percentage has the antibacterial activity of resisting gram-positive bacteria and Gram-negative bacteria fast and effeciently, control virus is class C disease active not enough particularly.Extremely important for the many virus-mediated transmissions of disease of control on the skin with abiotic lip-deep virus control.

[0088] for example, rhinovirus is and the relevant most important microorganism of acute respiratory disease that is called " (common) flu ".Also known other virus can cause the symptom of " common cold " such as parainfluenza virus, Respiratory Syncytial Virus(RSV) (RSV), enterovirus and coronavirus, but rhinovirus causes the common cold of maximum quantity in theory.The class norwalk virus causes human acute gastroenteritis, and it is the virus infections of main report after the common cold.The class norwalk virus is one of virus the most rambunctious, has in 10ppm chlorine and the ability of wide temperature range survival.Although begun to understand the molecular biology of class norwalk virus, also do not have to find to be used to prevent the enteric infection that causes by the class norwalk virus and be used to prevent the class norwalk virus to spread to the experimenter's who does not infect effective ways.

[0089] chlorine (that is, greater than 1000ppm) of well-known glutaraldehyde (gluteraldehyde), iodine or high concentration is the effective agent of anti-class norwalk virus.The phenol of high concentration, peracetic acid and hydrogen peroxide also can be controlled the class norwalk virus.The time of contact of using ethanol control class norwalk virus to grow.There is not a kind of can the use continuously especially for human skin in these methods with control class norwalk virus.Therefore, research is sent immediately and the composition of the activity of anti-enduringly class norwalk virus will be effective for reducing the gastroenteritis incident.Equally, the topical application of compositions that demonstrates the antiviral activity of anti-class norwalk virus will be effective for preventing and/or treating the disease that is caused by other calicivirus.

[0090] killing the virus finger can deactivation or break virus.Term " permanent disease-resistant poison effect " or " permanent disease-resistant cytotoxic activity " refer to after using residue is retained in lived (for example skin) or abiotic surface or give its situation as used herein, the time that it can provide antiviral activity significantly to prolong.In certain embodiments, " permanent disease-resistant poison effect " or " permanent disease-resistant cytotoxic activity " refer to that the stop residue or the film that will comprise the organic acid antivirotic after using are retained in lived (for example skin) or abiotic surface, and it provides the time of antiviral activity prolongation significantly.Described residue or the film of stopping can be continuously or continuous basically, and removing from treatment surface between antagonism water flush period.

[0091] composition of the present invention preferably provides lasting antiviral efficacy, and promptly preferably log is reduced by at least 2 in back 30 seconds contacting with described composition.With after described composition contacts, antiviral activity preferably keep at least about 0.5 hour, preferably at least about 1 hour, more preferably at least about 2 hours, at least about 3 hours with at least about 4 hours.In certain preferred aspects, with after described composition contacts, antiviral activity kept about six to about eight hours.In certain embodiments, described lasting antiviral activity due to (to small part due to) be present in the barrier film of lip-deep composition of processing or the organic acid bank in the film.Measure the lasting employed method of antiviral efficacy in following discussion.

[0092] antimicrobial compositions of the present invention is providing fast and the bacterial control of wide spectrum and control in the class norwalk virus highly effective fast and preferably enduringly.Described height effective composition is included in (a) the sterilization alcohol in the phase stabilization formulations, the organic acid of the effective dose of (b) killing the virus, and (c) optional active antimicrobial agent and (d) gelling agent are preferably with the saturated percent concentration of height.Astoundingly, described composition is to the skin gentleness and to abiotic surperficial non-corrosiveness.Therefore, provide the gentleness that solves bacterium and class norwalk virus control problem composition effectively to the user.

[0093] the pure and mild log P of sterilization less than about 1 organic acid synergy with control class norwalk virus.The pure and mild log P that sterilizes be 1 or bigger organic acid synergy with the control broad spectrum of bacteria.Comprise log P less than 1 first organic acid and log P be 1 or the second bigger organic acid composition play synergy with control class norwalk virus and wide spectrum gram-positive bacteria and Gram-negative bacteria.

[0094] antimicrobial compositions of the present invention family's clean applications (for example crust such as floor, table top, bathtub, plate and soft cloth material such as clothes), personal care applications (for example lotion, shower gels, soap, shampoo and cleaning piece) and commercial Application, entertainment applications and healthcare applications (for example on the tourism passenger steamer, in sanatorium, in food processing and sterilization instrument, medical device and gloves) in highly effective.Composition of the present invention can be effectively and apace cleaning and disinfection infected or surfaces contaminated by Gram-negative bacteria, gram-positive bacteria and class norwalk virus.Composition of the present invention preferably provides the effect of lasting anti-class norwalk virus.

[0095] composition of the present invention can be in external and use in vivo.External finger is in inanimate objects or on it, particularly on the inanimate objects of crust that is positioned at or uses with expectation prevention virus disseminating wherein or pressure release surface, on the object that the most human hand contacts.Refer in the body in lived object or on it, particularly on mammal skin, particularly on hand.

[0096] as setting forth in following nonrestrictive embodiment, antimicrobial compositions of the present invention comprises: (a) the about 25% sterilization alcohol to about 95% weight; (b) the kill the virus organic acid of effective dose, preferred organic acid combination; (c) water.In preferred embodiments, described composition comprises optional gelling agent and/or optional active antimicrobial agent.The pH that described composition has typically can form the continuous basically film or the layer of non-volatile composition component for less than about 5 on the surface of handling.After using, the tolerance in several hrs of described film or layer removed from the surface of handling.Especially, after flushing ten times, the composition components of effective dose is retained on the surface of processing, and after flushing three times, at least 50%, preferably at least 60% and more preferably at least 70% non-volatile composition components is retained on the surface of processing.

[0097] handle therein in the embodiment of skin, " flushing " refers to be about 30 ℃ and flowed down the skin that dabs processing about 30 seconds, air-dry then skin to about 40 ℃ running water in the temperature that has of appropriateness.Described therein composition comprises in the embodiment of active antimicrobial agent that when when measuring down for 25 ℃, antimicrobial is preferably at least about 50% at the saturated percentage of continuous aqueous phase.

[0098] described composition can further comprise optional hydrotropic agent and/or polyhydroxyl solvents and optional in addition after this disclosed composition such as pH regulator agent, dyestuff, skin conditioning agent, vitamin and spices.Composition of the present invention does not typically contain the surfactant of intentional adding, promptly comprises 0% to the surface-active compound of demonstrating of about 0.5% weight.

[0099] described compositions display goes out in contact and reduces about 2 at the log of gram-positive bacteria after 30 seconds.Described composition also demonstrates in contact and reduces about 2.5 at the log of Gram-negative bacteria after 30 seconds.Described composition further demonstrates in contact and reduces about 3 at the log of class norwalk virus and other calicivirus after 30 seconds, and preferably after contact, be reduced by at least 2.5 at these viral log in about five hours, and after contacting, be reduced by at least 2 at these viral log in about six to eight hours.Described composition also is gentle, does not need to wash or wipe out said composition from skin.

[00100] following compositions is present in the antimicrobial compositions of the present invention.

A. sterilization is pure

[00101] antimicrobial compositions of the present invention comprises the about 25% sterilization alcohol to about 75% weight.Embodiment preferred comprises the about 30% sterilization alcohol to about 75% weight.The most preferred embodiment comprises the about 30% sterilization alcohol to about 70% weight.

[00102] term " sterilization alcohol " is to comprise the water miscible alcohol to six carbon atom, i.e. C as used herein _1-6Alcohol.Sterilization alcohol includes, but are not limited to methyl alcohol, ethanol, propyl alcohol and isopropyl alcohol.

B. organic acid

[00103] antimicrobial compositions of the present invention comprises the organic acid of the amount that is enough to control the lip-deep class norwalk virus that contacts with this antimicrobial compositions with deactivation and bacterium.Described organic acid and described sterilization alcohol synergy are controlled class norwalk virus and bacterium apace to provide, and preferably control the class norwalk virus enduringly.

[00104] especially, described organic acid is present in the described composition with enough amounts, makes the pH lived or abiotic surface of said composition contact be reduced to the degree that wherein obtains lasting virus control.No matter described composition can both obtain lasting virus control whether from the contact-making surface flushing or allow to be retained in contact-making surface.Described organic acid does not dissociate at least partially in keeping in the composition, and when said composition diluted or use and flush period between still keep so.

[00105] in the time of on being applied to surface ratio such as human skin, this surperficial pH sufficiently reduces so that obtain lasting virus control.In preferred embodiments, the organic acid of residual volume is retained on the skin, even after rinsing step, preferably forms film or layer, to give lasting virus control.Yet even described organic acid washes from the surface basically fully, this surperficial pH is also enough low to give virus control at least 0.5 hour.

[00106] a kind of preferred compositions is a flushing-free type composition, does not promptly mean and washes from skin.Yet after flushing three times, at least 50% non-volatile composition components keeps from the teeth outwards, and after flushing 10 times, the composition of effective dose is retained on the surface of processing.

[00107] typically, organic acid be present in amount in the composition of the present invention be described composition about 0.05% to about 15%, preferred about 0.1% to about 10% weight.In order to obtain all advantages of the present invention, the organic acid amount be described composition about 0.15% to about 6% weight.In embodiment preferred, the organic acid mixture is added in the composition.The character of the total amount of organic acid in composition and used organic acid kind and used specific acid is relevant.

[00108] organic acid of adding antimicrobial compositions of the present invention preferably can not penetrate the surface that it is used, for example, be retained on the skin surface and can transdermal, and with other non-volatile composition components for example optional gelling agent and/or active antimicrobial agent cambium or film on skin.Therefore, described organic acid is preferably the hydrophobicity organic acid.

[00109] in one embodiment of the invention, the log P that described organic acid has is less than 1, preferably less than 0.75.In order to obtain all advantages of the present invention, described organic acid log P is less than 0.5.In this embodiment, the pure and mild organic acid synergy of described sterilization is to provide effective and lasting virus control.

[00110] in another embodiment, the log P that described organic acid has is 1 or bigger, for example 1 to about 100.In this embodiment, the pure and mild organic acid of described sterilization is controlled nonenveloped virus effectively and is acted synergistically with the control broad spectrum of bacteria.

[00111] imagination is 1 or the second bigger organic acid by thinking in the composition of the present invention to add log less than 1 first organic acid and log, and first kind and second organic acid and described sterilization be pure to act synergistically with the lasting control that the class norwalk virus is provided and the bacterial control of wide spectrum.

[00112] term " log P " is defined as the log of water-octanol distribution coefficient, i.e. P as used herein _w/ P _oThe log of ratio, wherein P _wFor under 25 ℃, under poised state, the concentration of organic acid in water, P _oFor under 25 ℃, the concentration of organic acid in octanol under poised state.Water-octanol coefficient can pass through U.S.Environmental Protection AgencyProcedure, ＂ OPPTS 830.7560 Partition Coefficient (n-Octanol/Water), and Generator Column Method ＂ (1996) measures.

[00113] log P typically is water-insolublely less than 1 organic acid, and for example water-soluble under 25 ℃ is less than about 0.5wt%.Log P be 1 or bigger organic acid typically be considered to water miscible, for example have water-soluble under 25 ℃ and be 0.5wt% at least.

[00114] antimicrobial compositions of the present invention can with organic acid comprise monocarboxylic acid, polycarboxylic acid, have a plurality of carboxyls, polymeric acid or its mixture of phosphate radical, sulfonate radical and/or sulfate radical part.Except acid moieties, described organic acid also can comprise other parts, for example hydroxyl and/or amino.In addition, organic acid anhydride can be used as organic acid and is used for composition of the present invention.Preferred organic acid is polycarboxylic acid, polymerization of carboxylic acid class and composition thereof.

[00115] in one embodiment, described organic acid comprises having structure RCO ₂The monocarboxylic acid of H, wherein R is C _1-10Alkyl, hydroxyl C _1-3Alkyl, halogen C _1-3The phenyl of alkyl, phenyl or replacement.Described monocarboxylic acid is water-soluble 0.05% weight that is at least about under 25 ℃ preferably.Alkyl can be replaced by phenyl and/or phenoxy group, and these phenyl and phenoxy group can be that replace or unsubstituted.

[00116] limiting examples of the used monocarboxylic acid of the present invention be acetate, propionic acid, sad, glycolic acid, lactic acid, benzoic acid, phenylacetic acid, phenoxyacetic acid, zimanic acid, 2-, 3-or 4 hydroxybenzoic acids, the benzoyl amino acid that contracts (anilic acid), adjacent-,-or 4-Chlorophenylacetic acid, neighbour-,-or parachlorophen-oxyacetic acid and composition thereof.The benzoic acid of Qu Daiing is disclosed in U.S. Patent No. 6,294 in addition, in 186, is incorporated by reference this paper.The benzoic example that replaces comprises, but be not limited to salicylic acid, 2-nitrobenzoic acid, thiosalicylic acid, 2,6-dihydroxy-benzoic acid, 5-nitro-salicylic acid, 5 bromosalicylic acid, 5-iodo-salicylic acid, 5-fluorosalicylic acid, 3-chloro-salicylic acid, 4-chloro-salicylic acid, 5-chloro-salicylic acid and composition thereof.

[00117] in another embodiment, described organic acid comprises polycarboxylic acid.Described polycarboxylic acid comprises at least two and four carboxylic acid groups at the most.Described polycarboxylic acid also can comprise hydroxyl or amino, and that replace and unsubstituted phenyl.Preferably, water-soluble be at least about 0.05% weight of described polycarboxylic acid under 25 ℃.

[00118] the used polycarboxylic limiting examples of the present invention comprises malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, decanedioic acid, fumaric acid, maleic acid, tartaric acid, malic acid, maleic acid, citric acid, aconitic acid and composition thereof.

[00119] acid anhydrides of polycarboxylic acid and monocarboxylic acid also is an organic acid useful in the composition of the present invention.Preferred acid anhydrides is polycarboxylic acid anhydrides.Because the pH of described composition, at least a portion acid anhydrides is hydrolyzed into carboxylic acid.The imagination acid anhydrides can hydrolysis at leisure on the surface of described composition contact, thereby helps to provide lasting antiviral activity.

[00120] in the 3rd embodiment, described organic acid comprises polymerization of carboxylic acid, polymerization sulfonic acid, sulfated polymers, polymer phosphate and composition thereof.The molecular weight that described polymeric acid has is about 500g/mol to 10,000, and 000g/mol comprises homopolymers, copolymer and composition thereof.Described polymeric acid preferably can form substantive film on skin surface, and the glass transition temperature T that has _gFor less than about 25 ℃,, be more preferably less than about 15 ℃ preferably less than about 20 ℃.Described glass transition temperature is transformed into the temperature of plastic state from the brittle glass attitude such as polymer for amorphous materials wherein.The Tg of polymer uses standard technique to measure by those skilled in the art easily.

[00121] described polymeric acid is that uncrosslinked or only very low limit is crosslinked.Therefore, described polymeric acid is a water dissolvable or water is dispersible at least.Described polymeric acid is typically by having the ethylenically unsaturated monomers preparation of at least one hydrophilic parts such as carboxyl, carboxylic acid anhydride, sulfonic acid and sulfate radical.

[00122] example that is usually used in preparing the monomer of described polyorganic acid includes, but are not limited to:

(a) contain carboxylic monomer, for example undersaturated monocarboxylic acid of monoene class or polycarboxylic acid are such as acrylic acid, methacrylic acid, maleic acid, fumaric acid, crotonic acid, sorbic acid, itaconic acid, ethylacrylic acid (ethacrylic acid), α-Lv Bingxisuan, alpha-cyanoacrylate, Beta-methyl acrylic acid (crotonic acid), atropic acid, β-propenyloxy group propionic acid, sorbic acid, α-chlorine sorbic acid, angelic acid, cinnamic acid, to chloro-cinnamic acid, β-stearyl acrylic acid, citraconic acid, mesaconic acid, glutaconate, aconitic acid, three carboxyl ethene and cinnamic acids;

(b) contain the monomer of carboxylic acid anhydride group, the undersaturated polycarboxylic acid acid anhydrides of monoene class for example, such as maleic anhydride and

(c) contain sulfonic monomer, for example aliphatic or aromatic ethenyl sulfonic acid are such as vinyl sulfonic acid, allyl sulphonic acid, vinyl toluene sulfonic acid, styrene sulfonic acid, (methyl) sulfoethyl acrylate, 2-acrylamido-2-methyl propane sulfonic acid, (methyl) acrylic acid sulfopropyl ester and 2-hydroxyl-3-(methyl) propenyloxy group propyl sulfonic acid.

[00123] but described polymeric acid can comprise the unit of other copolymerization well-known in the art, i.e. the undersaturated comonomer of other monoene class, as long as described polymer has basically, promptly have at least 10% and preferred at least 25% contain the acidic group monomeric unit.In order to obtain whole advantage of the present invention, described polymeric acid comprise at least 50%, more preferably at least 75% and at the most 100% contain the acidic group monomeric unit.But the unit of other copolymerization can be for example styrene, alkyl acrylate or alkyl methacrylate.

[00124] polymeric acid helps to form residual organic acid film or layer on skin, and helps further to form on skin the more continuous layer of residual organic acid.Described polymeric acid typically is used in combination with monocarboxylic acid and/or polycarboxylic acid.

[00125] a kind of preferred polymeric acid is a polyacrylic acid, is homopolymers or copolymer, for example the copolymer of acrylic acid and alkyl acrylate and/or alkyl methacrylate.Another kind of preferred polymeric acid is the homopolymers or the copolymer of methacrylic acid.

[00126] the used exemplary polymeric acid of the present invention includes, but are not limited to

Carbomer	(CARBOPOL 910，934， 934P，940，941，ETD 2050；ULTREZ 10，21)
		Acrylate/C20-30 alkyl acrylate cross-linked polymer	(ULTREZ 20)
Acrylate/Beheneth 20 methacrylate copolymers	(ACULYN 28)
		Acrylate/Steareth 20 methacrylate copolymers	(ACULYN 22)
Acrylate/Steareth 20 methacrylate cross-linked polymers	(ACULYN 88)
		Acrylate copolymer	(CAPIGEL 98)
Acrylate copolymer	(AVALURE AC)
		Acrylate/Palmeth 25 acrylate copolymers	(SYNTHALEN 2000)
The ammonium acrylate copolymer
		PAA/vinyl alcohol copolymer
Sodium polymethacrylate
		Acrylamido propyl group three ammonium chlorides (acrylamidopropyltrimonium chloride)/acrylate copolymer
Acrylate/acrylamide copolymer
		Acrylate/ammonio methacrylate copolymer
Acrylate/C10-30 alkyl acrylate cross-linked polymer
		Acrylate/biacetone acrylamide copolymer
Acrylate/octyl acrylamide copolymer
		Acrylate/VA copolymer
Acrylic acid/Acrylonitrogens copolymer

[00127] in an embodiment preferred of the present invention, described organic acid comprises one or more polycarboxylic acids, for example citric acid, malic acid, tartaric acid or any two or all three kinds these sour mixtures, or the polymeric acid that contains a plurality of carboxyls for example homopolymers and the copolymer of acrylic or methacrylic acid.

C. antimicrobial

[00128] described composition can also comprise optional active antimicrobial agent, the for example phenol and the phenolic compound of biguanides (for example Chlorhexidine digluconate), diphenyl compounds, phenmethylol, three halogenated diphenyl ureas, quaternary ammonium compound, ethoxylation, such as the phenolic compound of halogen-replacement such as PCMX (promptly to chloro-meta-xylene phenol) and triclosan (promptly 2,4,4 '-three chloro-2 '-dihydroxy diphenyl ether).Described antimicrobial also can be hydrogen peroxide, benzoyl peroxide (benzylperoxide), phenmethylol or quaternary ammonium compound.If exist, active antimicrobial compositions the amount in the composition of the present invention of joining is about 0.001% to about 1% weight.The antimicrobial of preferred optional is the phenols and the diphenyl compounds of following example.

[00129] amount of antimicrobial in composition of the present invention is about 0.001% to about 5%, preferred about 0.01% to about 2% of described composition weight.In order to obtain all advantages of the present invention, the amount of antimicrobial is about 0.05% to about 1% of a described composition weight.

[00130] described antimicrobial compositions can be instant (ready to use) composition, its typically comprise account for said composition weight 0.001% to about 2%, preferred 0.01% to about 1.5%, 0.05% to about 1% antimicrobial most preferably from about.Described antimicrobial compositions also can be formulated into concentrate, promptly dilutes so that the composition of final use to be provided than about 100 parts water by 1 part before use.Described concentrated composition typically comprises greater than about 0.1% to the antimicrobial of about 5% weight at the most.Consider that also the wherein final composition that uses comprises the active antimicrobial agent greater than 2% weight.

[00131] as discussed above, the absolute quantity of antimicrobial in described composition is very important, because it is the amount of obtainable antimicrobial in described composition.The amount of obtainable antimicrobial relates to content and the gelling agent and existence and the content of other optional ingredients in composition of antimicrobial in sterilize in the composition pure character, the composition in described composition.

[00132] for obtain short time of contact as 15 to 60 seconds in the killing bacteria of expectation, the continuous water of described composition preferably comprises a certain amount of antimicrobial, this amount position is when at room temperature measuring, the saturated concentration of described antimicrobial in water is at least about 50%, preferably at least about 60%, more preferably at least about 75%.In order to obtain all advantages of the present invention, described continuous water is saturated to about 95% to 100% by described antimicrobial.The method of measuring the saturated percentage of antibacterial agent in composition is following open.

[00133] the used antimicrobial of the present invention is the phenolic compound by the compound example of following type:

[00134] (a) 2-hydroxydiphenyl compounds

Wherein Y is or bromine, and Z is SO ₃H, NO ₂Or C ₁-C ₄Alkyl, r are 0 to 3, and o is 0 to 3, and p is 0 or 1, m be 0 or 1 and n be 0 or 1.

[00135] in preferred embodiments, Y is a chlorine or bromine, and m is 0, and n is 0 or 1, and o is 1 or 2, r be 1 or 2 and p be 0.

[00136] in particularly preferred embodiments, Y is a chlorine, and m is 0, and n is 0, and o is 1, r be 2 and p be 0.

[00137] useful especially 2-hydroxydiphenyl compounds has structure:

Have the title triclosan and the commercially available title IRGASAN DP300 of employing, be sold by CibaSpecialty Chemicals Corp., Greensboro, NC.Another kind of useful 2-hydroxydiphenyl compounds is 2,2 '-dihydroxy-5,5 '-two bromo-diphenyl ether.

[00138] (b) phenol derivatives

R wherein ₁Be hydrogen, hydroxyl, C ₁-C ₄Alkyl, chlorine, nitro, phenyl or benzyl; R ₂Be hydrogen, hydroxyl, C ₁-C ₆Alkyl or halogen; R ₃Be hydrogen, C ₁-C ₆Alkyl, hydroxyl, chlorine, nitro or with the sulphur of alkali metal salts or ammonium salt form; R ₄Be hydrogen or methyl; And R ₅Be hydrogen or nitro.Halogen is bromine or preferred chlorine.

[00139] instantiation of phenol derivatives comprises, but be not limited to chlorophenol (adjacent-,-, right-), 2,4 dichloro benzene phenol, right-nitrophenol, picric acid, xylenols, to chloro-meta-xylene phenol, cresols (adjacent-,-, right-), to chloro-m-cresol, catechol, Resorcino, 4-n-hexyl resorcinol, 1,2,3,-thrihydroxy-benzene, phloroglucin, carvacrol, thymol, to chlorothymol, o-phenyl phenol, 2-methane, to chloro-2-methane, phenol, 4-ethyl-phenol and 4-phenolsulfonic acid.Other phenol derivatives is in U.S. Patent No. 6,436, lists in 885, is incorporated by reference this paper.

[00140] (c) diphenyl compounds

Wherein X is sulphur or methylene, R ₆And R ' ₆Be hydroxyl, and R ₇, R ' ₇, R ₈, R ' ₈, R ₉, R ' ₉, R ₁₀And R ' ₁₀Be hydrogen or halogen independently of one another.Especially, the limiting examples of diphenyl compounds is hexachlorophene, tetra-chloro-phenol, two chlorophenols, 2,3-dihydroxy-5,5 '-two chloro diphenyl sulfides, 2,2 '-dihydroxy-3,3 ', 5,5 '-tetrachloro diphenyl sulfide, 2,2 '-dihydroxy-3,5 ', 5,5 ', 6,6 '-chlordene diphenyl sulfide and 3,3 '-two bromo-5,5 '-two chloro-2,2 '-dihydroxy diphenylamine.Other diphenyl compounds is in U.S. Patent No. 6,436, lists in 885, is incorporated by reference this paper.

[00141] (d) quaternary ammonium antibacterial agent

[00142] useful quaternary ammonium antibacterial agent has formula:

R wherein ₁₁, R ₁₂, R ₁₃And R ₁₄In at least one is alkyl, aryl or the alkaryl substituting group that comprises 6 to 26 carbon atoms.Alternatively, any two R substituting groups can be joined together to form five with nitrogen-atoms-or six-first cycloaliphatic ring or aromatic rings.Preferably, the molecular weight that partly has of all ammonium cations of antibacterial agent is at least 165.

[00143] described substituent R ₁₁, R ₁₂, R ₁₃And R ₁₄Can be straight chain can be side chain maybe, but be preferably straight chain, and can comprise that one or more acid amides, ether or ester bond connect.Especially, at least one substituting group is C ₆-C ₂₆Alkyl, C ₆-C ₂₆Alkoxy aryl, C ₆-C ₂₆The C of alkaryl, halogen-replacement ₆-C ₂₆Alkaryl, C ₆-C ₂₆Alkyl phenoxy alkyl etc.Non-above-mentioned substituent remaining substituting group typically comprises and is no more than 12 carbon atoms on the quaternary nitrogen atoms.In addition, the nitrogen-atoms of quaternary ammonium antibacterial agent may reside in the ring system, and aliphatic ring system is piperidyl or aromatic ring system pyridine radicals for example for example.Anion X can be that any quaternary ammonium compound that makes is water miscible one-tenth salt anionic.Anion includes, but are not limited to halide for example chlorion, bromide ion or iodide ion, methyl-sulfuric acid root and acetate thing root.

[00144] preferred quaternary ammonium antibacterial agent has structure:

R wherein ₁₂And R ₁₃Be C independently ₈-C ₁₂Alkyl, perhaps R ₁₂Be C ₁₂-C ₁₆Alkyl, C ₈-C ₁₈Alkyl ethoxy or C ₈-C ₁₈The alkyl phenyl ethyoxyl, R ₁₃For benzyl and X are halogen, methyl-sulfuric acid root, etherosulfuric acid root or right-tosylate.Alkyl R ₁₂And R ₁₃Can be straight chain or side chain, be preferably straight chain.

[00145] the quaternary ammonium antibacterial agent in composition of the present invention can be the independent quaternary ammonium compound or the mixture of two or more quaternary ammonium compounds.Useful especially quaternary ammonium antibacterial agent comprises dialkyl group (C ₈-C ₁₀) alkyl dimethyl ammonium chloride (for example Quaternium 24), zephiran (for example benzalkonium chloride and myristyl dimethyl benzene ammonio methacrylate), alkyl methyl lauryl benzyl ammonium chloride, methyl lauryl dimethylbenzene-two-trimethyl ammonium chloride, benzethonium chloride, dialkyl methyl benzyl ammonium chloride, alkyl dimethyl ethyl ammonium bromide and alkyl tertiary amine.Polymeric quaternary ammonium compound based on these monomer structures also can be used for the present invention.An example of polymeric quaternary ammonium compound is 2-cyclobutenyl alkyl dimethyl ammonium chloride polymer for example.Above-mentioned quaternary ammonium compound by supplier such as Lonza, Inc., Fairlawn, NJ and Stepan Co., Northfield, IL sells with following trade name:

With

The other example of quaternary ammonium antibacterial agent includes, but are not limited to alkyl ammonium halide such as the 16 basic trimethylammonium bromides of washing; The alkylaryl ammonium halide is such as octadecyl dimethyl benzyl ammonium bromide; N-alkyl pyridine halide is such as N-cetyl pyridine bromide; Deng.Other suitable quaternary ammonium antibacterial agent has acid amides, ether or ester moiety, such as Octylphenoxy ethoxyethyl group dimethyl benzyl ammonium chloride, N-(lauryl cocoyl carbamyl ylmethyl) pyridinium chloride etc.The quaternary ammonium antibacterial agent of other type comprises those of the aryl nucleus that comprises replacement, for example bay oxygen base phenyl trimethyl ammonium chloride, cetyl aminophenyl trimethyl first ammonium sulfide, dodecylphenyl trimethyl first ammonium sulfide, dodecylbenzyl trimethyl ammonium chloride, chlorination dodecylbenzyl trimethyl ammonium chloride etc.

[00146] concrete quaternary ammonium antibacterial agent includes, but are not limited to Shan Yu base dimethyl benzyl ammonium chloride (behenalkonium chloride), cetalkonium chloride, cetarylalkoniumbromide, softex kw (cetrimonium tosylate), cetyl pyridinium chloride, Laura bromine ammonium (lauralkonium bromide), Lauralkonium Chloride (lauralkoniumchloride), lapirium chloride (lapyrium chloride), lauryl chloride pyridine drone (laurylpyridinium chloride), myristyl ammonium chloride (myristalkonium chloride), oil base benzyl dimethyl ammonium chloride (olealkonium chloride) and iso stearyl ethyl dichloride ammonium.Preferred quaternary ammonium antibacterial agent comprises benzalkonium chloride, benzethonium chloride, cetyl bromination pyridine and Methylbenzethonium Chloride.

[00147] (e) aniline and biguanides antibacterial agent

[00148] useful aniline and biguanides (bisguanadine) antibacterial agent include but not limited to neko, carbanilide, salicylanilide, Tribromsalan, TCSA, Flusalan, chlorhexidine gluconate, chlorhexidine salt acidulants and composition thereof.

D. gelling agent

[00149] antimicrobial compositions of the present invention also comprises 0% to about 5% weight, preferred 0.10% gelling agent to about 3% weight.In order to obtain all advantages of the present invention, described antimicrobial compositions comprises about 0.25% gelling agent to about 2.5% weight.Described antimicrobial compositions typically comprises the gelling agent of q.s, makes that described composition is viscous liquid, gel or semisolid, its can be applied in easily with obliterating on skin or other surface.Those skilled in the art recognize that the type and the quantity that are included in the gelling agent in the described composition can provide compositions desired viscosity or denseness.

[00150] term " gelling agent " as this paper and use after this refers to that the viscosity that can increase aqueous composition maybe can be transformed into aqueous composition gel or semisolid compound.Therefore, described gelling agent can be a natural organic matter, and for example natural gum or synthetic polymer perhaps can be the natural inorganic things.

[00151] as mentioned above, composition of the present invention does not preferably contain surfactant.Surfactant is not deliberately joined in the antimicrobial compositions of the present invention usually, but can exist with 0% amount to about 0.5% weight, because surfactant may be present in the gelling agent of commercial form to help gelling agent to be dispersed in the water.Surfactant can also be present in other the composition components as additive or by product.

[00152] preferably, surfactant is dispensed from composition of the present invention to help avoid micella formation, it is solubilising active antimicrobial agent compound and its effect of reduction again.Similarly, preferred gelling agent is not for forming micella and can or not combining, or can not influence on the contrary those of anti-microbial properties of antimicrobial with the active antimicrobial agent complexing.In preferred embodiments, select the property quality and quantity of gelling agent and other composition components so that there be (when when measuring down for 25 ℃) in active antimicrobial agent (if existence) with at least 50% saturated amount.

[00153] following for can be used for the limiting examples of gelling agent of the present invention.Especially, following compound (organic compound and inorganic compound) mainly partly works by the water-based in thickening or the cementitious compositions:

Gum Arabic, agar, marine alga, alginic acid, ammonium alginate, ammonium chloride, ammonium sulfate, amylopectin, Attagel, swelled ground, C _9-15Alcohol, calcium acetate, calcium alginate, calcium carrageenan, calcium chloride, octanol, carboxymethyl hydroxyethyl cellulose, CMHPG, carrageenan, cellulose, cellulose gum, cetostearyl alcohol (cetearyl alcohol), cetanol, corn starch, hard gum, dextrin, dibenzylidene sorbitol (dibenzylidine sorbitol), the di-H tallow acid amides of ethene (ethylene dihydrogenated tallowamide), ethene two grease acid amides (ethylene dioleamide), ethene distearyl acid amides (ethylenedistearamide), fruit pectin, gelatin, guar gum, guar gum hydroxypropyl three ammonium chlorides (guar hydroxypropyltrimonium chloride), hectorite (hectorite), hyaluronic acid, hydrated silica, hydroxy butyl methyl cellulose, hydroxyethylcellulose, hydroxyethyl ethylcellulose, ethoxy stearmide-MIPA, hydroxypropyl cellulose, hydroxypropyl guar gum, hydroxypropyl methylcellulose, different cetanol, isooctadecanol, karaya, sea grass, laruyl alcohol, carob gum, aluminium-magnesium silicate, magnesium silicate, magnesium trisilicate, methoxyl group PEG-22/ Propylene glycol laurate copolymer, methylcellulose, microcrystalline cellulose, montmorillonite, myristyl alcohol, oat meal, oleyl alcohol, palm kernel alcohol, pectin, PEG-2M, PEG-5M, polyvinyl alcohol, potassium alginate, carrageenan potassium, potassium chloride, potassium sulphate, potato starch, propylene glycol alginate, Sensor Chip CM 5 sodium, carrageenan sodium, cellulose sodium sulfate, sodium chloride, sodium silicoaluminate, sodium sulphate, stearyl alkylammonium salt swelled ground (tearalkonium bentonite), stearyl alkylammonium salt hectorite (stearalkonium hectorite), stearyl alcohol, tallow alcohol, the TEA-hydrochloride, bassora gum, tridecanol, the tromethamine aluminium-magnesium silicate, wheat flour, wheaten starch, xanthans, polyvinylpyrrolidone and derivative thereof, vinethene derivative (methyl vinyl ether, ethyl vinyl ether, butyl vinyl ether, isobutylvinyl ether, poly-ethylene methacrylic ether/maleic acid), quaternised vinyl pyrrolidone/quaternised dimethyl aminoethyl pyrrolidones-based polyalcohol and methacrylate copolymer, caprolactam/vinyl pyrrolidone dimethylaminoethyl methacrylate polymers, vinyl pyrrolidone/dimethyl amino ethyl methacrylate copolymer, acid stable and derivative naturally occurring guar gum and modified guar, xanthans modification or that replace and carboxy-propyl cellulose and composition thereof.

[00154] the other limiting examples of following gelling agent mainly works by the non-aqueous part of thickener composition: abienol, acrylic linoleic acid behenic acid aluminium, aluminium octoate, dilinoleic acid aluminium, AlDS, isostearic acid aluminium/Aluminum trilaurate/aluminum palmitate or aluminum stearate, isostearic acid aluminium/aluminium myristate, isostearic acid aluminium/aluminum palmitate, isostearic acid aluminium/aluminum stearate, lanoceric acid aluminium (aluminum lanolate), aluminium myristate/aluminum palmitate, aluminum stearate, aluminum stearate, three aluminum foil stearates, beeswax behenamide behenyl alcohol, butadiene/acrylonitrile copolymer, C _29-70Acid behenic acid calcium; calcium stearate; candelila wax; babassu; ceresine; cholesterol; the hydroxy stearic acid cholesterol ester; lauric alcohol; copal; stearic acid malic acid two glyceride; dihydroabietyl alcohol; the dimethyllaurylamine oleate; dodecanedioic acid/cetostearyl alcohol (cetearyl alcohol)/diol copolymer; erucyl amide (erucamide); ethyl cellulose; glyceryl triacetyl hydroxy stearic acid ester; glyceryl triacetyl ricinoleate ester Er behenic acid diol ester; two sad diol esters; distearyl acid diol ester; distearyl acid hexylene glycol ester; hydrogenation C _6-14Olefin polymer, rilanit special, cotmar, hydrogenated fat, the hydrogenation pilchardine, hydrogenated palm kernel glyceride, the hydrogenated palm macadamia nut oil, HPO, Parleam, oil with hydrogenated soybean, hydrogenated oil and fat tallow acid amides, hydrogenated tallow glyceride, hydrogenated vegetable glyceride, hydrogenated vegetable glyceride, hydrogenated vegetable oil, hydroxypropyl cellulose, isobutene/isoprene copolymer, different cetyl stearoyl stearate, Japan wax, jojoba wax, lanolin alcohol, lauramide, the methyl dehydroabietate, the hydrogenated methyl rosinate, the methyl rosinate, methyl styrene/vinyl toluene copolymer, microwax, montanic acid wax (montan acidwax), montan wax, the myristyl eicosanol, the myristyl octadecanol, vaccenic acid/copolymer-maleic anhydride, octyl group dodecyl stearoyl stearate, oleamide, oleostearin, ouricury wax, the polyethylene of oxidation, ceresine, palm kernel alcohol, paraffin, hydrogenated rosins acid pentaerythritol ester, the abietic acid pentaerythritol ester, four abietic acid pentaerythritol ester Si behenic acid pentaerythritol esters, Pentaerythrityl tetraoctanoate, four pentaerythritol oleates, pentaerythritol tetrastearate, phthalic anhydride/glycerine/glycidyl capric acid copolymer, phthalic acid/1,2,4-benzenetricarboxylic acid/diol copolymer, polybutene, polybutylene terephthalate, poly-cinene, polyethylene, polyisobutene, polyisoprene, polyvinyl butyral resin, the polyvinyl laurate, two sad propylene glycol esters, two coconut oil propylene glycol esters (propylene glycol dicocoate), two different n-nonanoic acid propylene glycol esters, two lauric acid propylene glycol esters, two n-nonanoic acid propylene glycol esters, the distearyl acid propylene glycol ester, two hendecanoic acid propylene glycol esters, PVP/ eicosylene copolymer, PVP/ hexadecene copolymer, rice bran wax, stearyl alkylammonium salt bentonite (stearalkonium bentonite), stearyl quaternary ammonium alkyl montmorillonite (stearalkonium hectorite), stearmide, stearmide DEA-distearate, stearmide DIBA-stearate, stearmide MEA-stearate, stearone, stearyl alcohol, the stearyl erucyl amide, the stearic acid stearyl, stearyl stearoyl stearate, synthetic bees wax, synthetic wax, trihydroxy tristearin, three different fat in the ninth of the ten Heavenly Stems (triisononanoin), three different tristearin, three linoleic acid, three iso stearyl esters, trilaurin, three linoleic acid, trilinolein, trimyristin, triolein, glyceryl tripalmitate, tristearin, zinc laurate, Zinc tetradecanoate, zinc neodecanoate, abietic acid zinc, zinc stearate and composition thereof.

[00155] the used exemplary gelling agent of the present invention includes, but are not limited to

Polyethylene glycol ﹠ propane diols ﹠ water	(ACULYN 44)
		Acrylate dimethyl taurine ammonium/VP copolymer	(ARISTOFLEX AVC)
Tristerin ﹠ PEG 100 stearates	(ARLACEL 165)
		Polyethylene (2) stearyl ether	(BRIJ 72)
Polyoxyethylene (21) stearyl ether	(BRIJ 721)
		Silica	(CAB-O-SIL)
Polyquaternium 10	(CELQUAT CS230M)
		Cetanol
Cetostearyl alcohol ﹠ Cetereth 20	(COSMOWAX P)
		Cetostearyl alcohol ﹠ di(2-ethylhexyl)phosphate cetyl ester ﹠ Ceteth-10 phosphate	(CRODAFOS CES)
Ceteth-20 phosphate ﹠ cetostearyl alcohol ﹠ di(2-ethylhexyl)phosphate cetyl ester	(CRODAFOS CS-20 Acid)
		Cetostearyl alcohol ﹠ Cetereth 20	(EMULGADE NI 1000)

Sodium silicate magnesium	(LAPONITE XLG)
		Cetanol ﹠ stearyl alcohol ﹠ stearyl alkyl ammomium chloride (Stearalkonium Chloride) ﹠ dimethyl octadecylamine ﹠ lactic acid	(MACKADET CBC)
Cetostearyl alcohol ﹠ 18 acylamino-propyl-dimethyl amine (Stearamidopropyldimethylamine) ﹠ 18 acylamino-propyl group alkyl ammomium chlorides (Stearamidopropylalkonium Chloride)	(MACKERNIUM Essential)
		The stearyl alkyl ammomium chloride	(MACKERNIUM SDC-85)
Cetostearyl alcohol ﹠ 18 acylamino-propyl-dimethyl amine ﹠ 18 acylamino-propyl group alkyl ammomium chloride ﹠ silicone (Silicone) Quaternium 16	(MACKERNIUM Ultra)
		Cetostearyl alcohol ﹠ cetearyl glucoside (Cetearyl Glucoside)	(MONTANOV 68EC)
Hydroxyethylcellulose	(NATROSOL 250 HHR CS)
		Polyquaternium-37 ﹠ Kuang Wuyou ﹠Trideceth-6	(SALCARE SC 95)
Polyquaternium-32 ﹠ Kuang Wuyou ﹠Trideceth-6	(SALCARE SC 96)
		Stearic acid
The cetyl hydroxyethylcellulose	(NATROSOL Plus 330 CS)
		Polyvinyl alcohol, PVP-K30, propane diols
Stearic acid ， behenic acid, tristerin, lecithin, C12-16 alcohol, palmitic acid	(PROLIPID 141)
		Beeswax	(saponification beeswax)
Beeswax	(synthetic bees wax)
		Water, beeswax, sesame oil, lecithin, methyl hydroxybenzoate	(royal jelly)
Polyquaternium 10	(CELQUAT SC240C)
		PAA/acryloyl group dimethyl sodium taurocholate copolymer ﹠ isohexadecane ﹠ polysorbate 80	(SIMULGEL EG)
Polyquaternium 44	(LUVIQUAT Care)

E. carrier

[00156] carrier of antimicrobial compositions of the present invention comprises water.

F. optional ingredients

[00157] antimicrobial compositions of the present invention also can comprise the well-known composition of optional those skilled in the art.Concrete optional ingredients that can in composition of the present invention, exist and the following discussion of amount.

[00158] described optional ingredients exists with enough amounts, this amount is enough to achieve the function of its expection and the antimicrobial efficacy that do not influence composition on the contrary, and the synergy that provides of the layer that forms on the surface of handling of the nonvolatile element of influence pure and mild organic acid of sterilization or described composition or film on the contrary not especially.Optional ingredients typically with account for composition weight 0% to about 50%, exist separately or together.

[00159] classification of optional ingredients includes, but are not limited to the optional member of hydrotropic agent, polyhydroxyl solvents, dyestuff, aromatic, pH regulator agent, thickener, viscosity modifier, chelating agent skin conditioning agent, emollient, preservative, vitamin, buffer, foam stabiliser, antioxidant, Babassuamidopropylamine, chelating agent, opacifier and similar type well known by persons skilled in the art.

[00160] if there is hydrotropic agent, its amount is about 0.1% to about 30%, preferred about 1% to about 20% of a described composition weight.In order to obtain all advantages of the present invention, composition can comprise about 2% hydrotropic agent to about 15% weight.

[00161] hydrotropic agent is the compound with the water miscible ability that increases other compound.Used in the present invention hydrotropic agent does not have surfactant properties, typically is the short-chain alkyl aromatic yl sulphonate.Hydrotropic instantiation includes, but are not limited to cumene sodium sulfonate, cumene ichthyodin, ammonium xylene sulfonate, potassium toluene sulfonate, toluenesulfonic acid sodium salt, sodium xylene sulfonate, toluenesulfonic acid and xylene monosulfonic acid.Other useful hydrotropic agent comprises poly-sodium naphthalene sulfonate, kayexalate, methyl naphthalene sulfonic acid sodium, sodium camphorsulfonate and disodium succinate.

[00162] if there is polyhydroxyl solvents, its amount is about 0.1% to about 50%, preferred about 5% to about 40% of a described composition weight.In order to obtain all advantages of the present invention, the amount of described polyhydroxyl solvents is about 10% to about 30% of a described composition weight.Form contrast with sterilization alcohol, if there is polyhydroxyl solvents, its contribution to the antimicrobial efficacy of composition of the present invention is very little.

[00163] " polyhydroxyl solvents " for comprising two to six, typically the water-soluble organic compounds of two or three hydroxyls.Term " water miscible " refers to that described polyhydroxyl solvents water-soluble under 25 ℃ is the water of polyhydroxyl solvents/100g of 0.1g at least.Described polyhydroxyl solvents water-soluble do not have the upper limit, and for example, described polyhydroxyl solvents and water can be miscible in any ratio.

[00164] therefore, term " polyhydroxyl solvents " comprises water miscible glycol, three pure and mild polyalcohols.The instantiation of hydroxyl solvent includes, but are not limited to ethylene glycol, propane diols, glycerine, diethylene glycol (DEG), dipropylene glycol, tripropylene glycol, hexylene glycol, butanediol, 1,2,6-hexane triol, sorbierite, PEG-4 and similar polyol.

[00165] particular type of optional member comprises inorganic phosphate, sulphate and the carbonate as buffer; EDTA and phosphate as chelating agent; With bronsted lowry acids and bases bronsted lowry as the pH regulator agent.

[00166] example of the preferred classes of Ren Xuan alkaline pH conditioning agent is an ammonia; Single-, two-and trialkylamine; Single-, two-and three-alkanolamine; Alkali metal and alkaline earth metal hydroxide; And composition thereof.Yet the character of described alkaline pH conditioning agent is unrestricted, can use any alkaline pH conditioning agent known in the art.Particularly, the limiting examples of alkaline pH conditioning agent is an ammonia; Sodium hydroxide, potassium hydroxide and lithium hydroxide; MEA; Triethylamine; Isopropanolamine; Diethanol amine; And triethanolamine.

[00167] example of the preferred classes of Ren Xuan acidic ph modifier is an inorganic acid.The limiting examples of inorganic acid is hydrochloric acid, nitric acid, phosphoric acid and sulfuric acid.The character of described acidic ph modifier is unrestricted, can be used alone or in combination any acidic ph modifier known in the art.

[00168] described composition also can comprise cosolvent or fining agent, is solvent or its mixture of the oxidation of about at the most 4000 polyethylene glycol, methyl propanediol, ethene, propylene or butylene such as molecular weight.When needs are given described composition stable and/or transparency, can add cosolvent or fining agent, its may reside in processing lip-deep composition residual film or the layer in.

[00169] surfactant with account for composition weight 0% to about 15%, 0.1% to about 10% the amount of typically being adds in the described composition.More typically, if exist, described composition comprises about 0.2% surfactant to about 7% weight.Described optional surfactant is stable under the pH of described composition, and with described composition in other composition of existing compatible.

[00170] described surfactant can be the compatibility mixture of anion surfactant, cationic surfactant, non-ionic surface active agent or surfactant.Described surfactant also can be that (its pH according to composition has anion or cationic property for ampholytic, amphoteric) surfactant in both sexes.

[00171] therefore, described composition can comprise the anion surfactant with hydrophobic parts and further possess hydrophilic property part, described hydrophobic parts is such as comprising about 8 to about 30 carbon atoms, particularly about 12 carbochains to about 20 carbon atoms, described hydrophilic parts is such as sulfate radical, sulfonate radical, carbonate, phosphate radical or carboxylate radical.Usually, described hydrophobicity carbochain, is reduced such as water-soluble increase or surface tension to give the specific physical property of anion surfactant such as with oxirane or expoxy propane etherificate by etherificate.

[00172] suitable anion surfactant includes, but are not limited to the compound such as the alkyl sulfate of known type; alkyl ether sulphate; the alkyl ether sulphonic acid ester; the sulfuric ester of alkyl phenoxy poly ethyleneoxy ethanol; the alpha-olefin sulphonic acid ester; β-alkoxy alkane sulphonic acid ester; alkyl aryl sulfonate; the alkyl glycerol Monosulfate; alkyl glycerol list sulphonic acid ester; alkyl carbonate; alkyl ether carboxylate; fatty acid; sulfosuccinate; sarcosinate; Octoxinol or nonoxinol phosphate; taurine ester (taurates); taurine fatty ester (fatty taurides); fatty acid amide polyoxyethylene sulfuric ester; isethionic acid ester; acyl glutamic acid ester; the salts of alkyl sulfoacetates ester; the peptide of acidylate; acyl lactylates (acyl lactylates); anion fluorinated surfactants and composition thereof.Other anion surfactant is at McCutcheon ' sEmulsifiers and Detergents, 1993 Annuals, (hereinafter be expressed as McCutcheon ' s), McCutcheon Division, MC Publishing Co., Glen Rock, NJ, provide in the 263-266 page or leaf, be incorporated by reference this paper.A large amount of other anion surfactant and the type of anion surfactant be disclosed in U.S. Patent No. 3,929,678 and U.S. Patent Publication No.2002/0098159 in, all incorporate this paper by reference into every piece.

[00173] especially, the non-limiting type of the used anion surfactant of the present invention includes, but are not limited to C ₈-C ₁₈Alkylsulfonate, C ₈-C ₁₈Alkyl sulfate, C ₈-C ₁₈Soap, has one or two mole ethyoxyl partial C ₈-C ₁₈Alkyl ether sulfate, C ₈-C ₁₈Amino alcohol oxide, C ₈-C ₁₈Alkanoyl sarcosinate, C ₈-C ₁₈Sulfosalicylic acetate, C ₈-C ₁₈Sulfosuccinate, C ₈-C ₁₈Alkyl diphenyl ether disulfonate, C ₈-C ₁₈Alkyl carbonate, C ₈-C ₁₈Alpha-alkene sulfonate, methyl ester sulfonate and composition thereof.Described C ₈-C ₁₈Alkyl comprises eight to 18 carbon atoms, and it can be (for example lauryl) of straight chain or (for example 2-ethylhexyl) of side chain.The cation of described anion surfactant can be alkali metal (preferred sodium or potassium), ammonium, C ₁-C ₄Alkylammonium (single-, two-, three-) or C ₁-C ₃Alkanol ammonium (single-, two-, three-).Can use lithium and alkaline earth cation (for example magnesium), but not be preferred.

[00174] concrete surfactant comprises, but is not limited to lauryl sulfate, sulfuric acid octyl group ester, sulfuric acid 2-ethylhexyl, sulfuric acid decyl ester, sulfuric acid tridecyl ester, cocounut oil ester, methyl amimoacetic acid lauroyl ester, sulfosuccinic acid Lauryl Ester, straight chain C ₁₀Diphenyl ether disulfonate, sulfosuccinic acid Lauryl Ester, lauryl ether sulfuric ester (1 and 2 moles of ethylene oxide), sulfuric acid myristyl ester, oleate, stearate, fatty acid ester, ricinoleate ester, sulfuric acid cetyl ester and similar surfactant.The other example of surfactant can be at " CTFACosmetic Ingredient Handbook; " J.M.Nikitakis edits, The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, D.C. (1988) (hereinafter being expressed as CTFA Handbook), 10-13,42-46 page or leaf and 87-94 page or leaf find, and are incorporated by reference this paper.

[00175] described composition can also comprise non-ionic surface active agent.Typically, non-ionic surface active agent has the hydrophobicity base, and such as chain alkyl or alkylating aryl, described hydrophilic chain comprises (promptly 1 to about 30) ethyoxyl and/or propoxyl group part of sufficient amount.The example of the type of non-ionic surface active agent comprises polyglycol ether, the polyglycol ether of sorbierite, ethylene oxide-propylene oxide block copolymer, the fat (C of ethoxylated alkylphenol, ethoxylation and propoxylated fatty alcohol, methyl glucoside ₈-C ₁₈) ethoxylation ester, oxirane and long-chain amine or the condensation product of acid amides and composition thereof of acid.

[00176] exemplary ionic surfactant pack is drawn together, but is not limited to methyl glucosamine polyethers (gluceth)-10, PEG-20 methyl glucoside distearate, PEG-20 Glucate SS, C _11-15Pareth-20, ceteth-8, ceteth-12, dodoxynol-12, laureth 9-15 (laureth-15), the PEG-20 castor oil, polysorbate 20, steareth-20, polyoxyethylene-10 cetyl ether, polyoxyethylene-10 stearoyl ether, polyoxyethylene-20 cetyl ether, polyoxyethylene-10 oleyl ether, polyoxyethylene-20 oleyl ether, ethoxylated nonylphenol, the ethoxylation octyl phenol, ethoxylation dodecylphenol or comprise the ethoxylated fat (C of 3 to 20 ethylene oxide moieties ₆-C ₂₂) alcohol, the different cetyl ether of polyoxyethylene-20, polyoxyethylene-23 glycerol monolaurate, polyoxyethylene-20 tristerin, the PPG-10 methyl glucose ether, the PPG-20 methyl glucose ether, polyoxyethylene-20 anhydro sorbitol monoesters, polyoxyethylene-80 castor oil, polyoxyethylene-15 tridecyl ether, polyoxyethylene-6 tridecyl ether, laureth 9 (laureth)-2, laureth 9-3, laureth 9-4, the PEG-3 castor oil, PEG 600 dioleates, PEG 400 dioleates and composition thereof.

[00177] other non-ionic surface active agent is disclosed in McCutcheon ' s in a large number, 1-246 and 266-272 page or leaf; CTFA International Cosmetic Ingredient Dictionary, the 4th edition, Cosmetic, Toiletry and Fragrance Association, Washington, D.C. (1991) (after this being called CTFA Dictionary) 1-651 page or leaf; With at CTFAHandbook, the 86-94 page or leaf is all incorporated this paper into by reference with every piece.

[00178] except anion and non-ionic surface active agent, (ampholytic, amphoteric) surfactant can be used in the described composition for cation, both sexes.Useful cationic surfactant comprises those with following structural formula:

R wherein ₁₅For having about 12 to the alkyl of about 30 carbon atoms or have about 12 aromatic groups, aryl or alkaryl to about 30 carbon atoms; R ₁₆, R ₁₇And R ₁₈Be independently selected from hydrogen, have 1 to the alkyl of about 22 carbon atoms or have about 12 aromatic groups, aryl or alkaryl to about 22 carbon atoms; With X be compatible anion, preferably be selected from chlorion, bromide ion, iodide ion, acetate, phosphate radical, nitrate anion, sulfate radical, methylsulfate, ethyl sulphate, tosylate, lactate, citrate, glycolic root and composition thereof.In addition, R ₁₅, R ₁₆, R ₁₇And R ₁₈Alkyl also can comprise ester bond and/or ehter bond, or hydroxyl or amino substituting group (for example, described alkyl can comprise polyethylene glycol and polypropylene glycol part).

[00179] preferably, R ₁₅For having about 12 alkyl to about 22 carbon atoms; R ₁₆For H or have 1 alkyl to about 22 carbon atoms; And R ₁₇And R ₁₈Be H or have 1 alkyl independently to about 3 carbon atoms.More preferably, R ₁₅For having about 12 alkyl to about 22 carbon atoms, and R ₁₆, R ₁₇And R ₁₈For H or have 1 alkyl to about 3 carbon atoms.

[00180] other useful cationic surfactant comprises amino-acid amides, wherein in said structure, and R ₁₀Be R alternatively ₁₉CONH-(CH ₂) _n, R wherein ₁₉For having about 12 alkyl and n to about 22 carbon atoms is integer 2 to 6, more preferably 2 to 4, most preferably 2 to 3.The limiting examples of these cationic surfactants comprises the amino propyl group pg dimonium chloride phosphate (stearamidopropyl PG-dimonium chloridephosphate) of stearoyl; mountain Yu acylamino-propyl group pg dimonium chloride (behenamidopropylPG-dimonium chloride), the amino propyl group ethyl Dimethyl Ammonium (stearamidopropyl ethyldimonium ethosulfate) of second thiosulfuric acid stearoyl, amino propyl-dimethyl (myristyl acetic acid esters) ammonium chloride of stearoyl, the amino propyl-dimethyl cetearyl ammonium tosylate (stearamidopropyl dimethyl cetearyl ammonium tosylate) of stearoyl, the amino propyl-dimethyl ammonium chloride of stearoyl, amino propyl-dimethyl ammonium lactate of stearoyl and composition thereof.

[00181] limiting examples of quaternary cationics comprises and is selected from following those: cetyl ammonium chloride, cetyl bromination ammonium, lauryl chlorination ammonium, lauryl bromination ammonium, stearoyl chlorination ammonium, the stearoyl ammonium bromide, the cetyl alkyl dimethyl ammonium chloride, cetyl dimethyl ammonium bromide, lauryl dimethyl ammonium chloride, the lauryl dimethyl ammonium bromide, the stearoyl alkyl dimethyl ammonium chloride, stearoyl dimethyl ammonium bromide, the cetyl trimethyl ammonium chloride, the cetyl trimethylammonium bromide, lauryl trimethyl ammonium chloride, the lauryl trimethylammonium bromide, stearyl trimethyl ammonium chloride, the stearoyl trimethylammonium bromide, lauryl dimethyl ammonium chloride, stearoyl dimethyl cetyl two tallow dimethyl ammonium chlorides, dicetyl ammonium chloride, the dicetyl ammonium bromide, dilauryl ammonium chloride, the dilauryl ammonium bromide, distearyl ammonium chloride, the distearyl ammonium bromide, the dicetyl ammonio methacrylate, dicetyl methyl ammonium bromide, the dilauryl ammonio methacrylate, dilauryl methyl ammonium bromide, the distearyl ammonio methacrylate, distearyl methyl ammonium bromide and composition thereof.

[00182] other quaternary ammonium salt comprises wherein C ₁₂-C ₃₀Alkyl carbon chain is from those of tallow fatty acid or cocoyl fatty acid.Term " tallow " refers to that a class derives from the alkyl of tallow fatty acid (being generally the acid of hydrogenated animal fat), and it has usually at C ₁₆To C ₁₈The mixture of the alkyl chain of scope." cocoyl (coconut) refers to that a class derives from the alkyl of cocoyl fatty acid to term, and it has usually at C ₁₂To C ₁₄The mixture of the alkyl chain of scope.The example of quaternary ammonium salt derives from these tallows and cocoyl source, comprises two tallow dimethyl ammonium chlorides, two tallow Dimethyl Ammonium Methylsulfates, two (hydrogenated tallow) alkyl dimethyl ammonium chloride, two (hydrogenated tallow) dimethyl acetic acid ammonium, two tallow dipropyl ammonium phosphate, two tallow dimethyl ammonium nitrate, two (cocoyl alkyl) alkyl dimethyl ammonium chloride, two (cocoyl alkyl) dimethyl ammonium bromide, tallow ammonium chloride, cocoyl ammonium chloride and composition thereof.Example with quaternary ammonium compound of the alkyl that contains ester bond is two tallow base oxethyl alkyl dimethyl ammonium chlorides.

[00183] both sexes (Ampholytic) surfactant (being both sexes (amphoteric) and amphion (zwitterionic) surfactant) can be described as having the secondary amine of straight or branched aliphatic group and the derivative of tertiary amine widely, wherein one of aliphatic substituting group comprises about 8 to about 18 carbon atoms, and at least one aliphatic substituting group comprises anionic water-solubilizing group, for example carboxyl, sulfonate radical or sulfate radical.

[00184] more particularly, a class amphoteric surfactant comprises sarcosinate and the taurate with following general structural formula:

R wherein ²⁰Be C ₁₁-C ₂₁Alkyl, R ²¹Be hydrogen or C ₁-C ₂Alkyl, Y are CO ₂M or SO ₃M, M are that alkali metal and n are numeral 1 to 3.

[00185] another kind of amphoteric surfactant is the acid amides sulfosuccinate with following structural formula:

[00186] also can use the amphoteric surfactant of following type:

Alkoxylate both sexes glycinate (alkoamphoglycinates)

Alkoxylate carboxyl glycinate (alkoamphocarboxyglycinates)

Alkoxylate both sexes propionate (Alkoamphopropionates)

Alkoxylate both sexes carboxyl propionate (alkoamphocarboxypropionates)

Alkoxylate both sexes propyl sulfonic acid salt (alkoamphopropylsulfonates)

Alkoxylate amido propyl betaine (alkamidopropyl betaines)

Alkoxylate acylamino-propyl hydroxy betain (alkamidopropyl hydroxysultaine)

Alkoxylate aminopropionate (alkylaminopropionates)

Alkoxylate iminopropinate (alkyliminopropionates)

The amphoteric surfactant of other type comprises phosphoric acid betaine (phosphobetaines) and phosphorous acid betain (phosphitaines).

[00187] especially; the limiting examples of the amphoteric surfactant that the present invention is used is a cocoyl N methyl taurine sodium; oil base N methyl taurine sodium; tall oil acid N methyl taurine sodium; palmityl N methyl taurine sodium; cocoyl dimethyl carboxymethyl betaine; the lauryl dimethyl carboxymethyl betaine; lauryl dimethyl carboxyethyl betain; cetyl dimethyl carboxymethyl betaine; lauryl-two (2-ethoxy) carboxymethyl betaine; oleoyl dimethyl γ-carboxymethyl CAB; lauryl-two-(2-hydroxypropyl)-carboxyethyl betain; cocoyl acylamino-dimethyl propyl sulfobetaines (sultaine); stearyl acylamino-dimethyl propyl sulfobetaines; lauryl acylamino--two-(2-ethoxy) propyl group sulfobetaines; oleamide PEG-2 disodium sulfosuccinate; the amino PEG-2 sulfosuccinate of TEA oleoyl; oleamide MEA disodium sulfosuccinate; oleamide MIPA disodium sulfosuccinate; castor oil acid amides MEA disodium sulfosuccinate; endecatylene acid amides MEA disodium sulfosuccinate (disodium undecylenamide MEA sulfosuccinate); wheat embryo acylamino-(wheat germamido) MEA sodium sulfosuccinate; wheat embryo acylamino-PEG-2 disodium sulfosuccinate; isostearoyl amine MEA disodium sulfosuccinate (disodiumisostearamideo MEA sulfosuccinate); cocoyl both sexes glycinate (cocoamphoglycinate); cocoyl both sexes carboxyl glycinate (cocoamphocarboxyglycinate); lauryl both sexes glycinate (lauroamphoglycinate); lauryl both sexes carboxyl glycinate (lauroamphocarboxyglycinate); octyl group both sexes carboxyl glycinate (capryloamphocarboxygly cinate); cocoyl both sexes propionate (cocoamphopropionate); cocoyl both sexes carboxyl propionate (cocoamphocarboxypropionate); lauryl both sexes carboxyl propionic ester (lauroamphocarboxypropionate); octyl group both sexes carboxyl propionate (capryloamphocarboxypropionate); dihydroxy ethyl tallow glycinate; cocoyl acylamino-3-hydroxypropyl phosphoric acid betaine disodium; lauryl myristyl acylamino-3-hydroxypropyl phosphoric acid betaine disodium; lauryl myristyl acylamino-glyceryl phosphoric acid betaine; lauryl myristyl acylamino-carboxyl 3-hydroxypropyl phosphoric acid betaine disodium; cocoyl acylamino-propyl group phosphorous acid betain list sodium (monosodium phosphitaine); lauryl myristyl acylamino-propyl group phosphorous acid betain list sodium and composition thereof.

[00188] useful amphoteric surfactant also comprises amine oxide.Amine oxide has wherein, and hydrophilic parts comprises the general structure that is bonded to the nitrogen-atoms of oxygen atom by semi-polar bond.

[00189] R ²², R ²³And R ²⁴Can be for having 1 alkyl or alkenyl to saturated or unsaturated, side chain or the non-side chain of about 24 carbon atoms.Preferred amine oxide comprises at least one R group, and it is the alkyl chain of 8 to 22 carbon atoms.The limiting examples of amine oxide comprises the alkyl-dimethyl amine oxide, such as decyl amine oxide, cocoyl amine oxide, myristyl amine oxide and palmityl amine oxide.Alkyl amino propyl group amine oxide for example cocoyl acylamino-propyl group amine oxide and stearyl acylamino-propyl group amine oxide also is useful.

[00190] limiting examples of used preferred surfactants comprises and is selected from following those in described composition: the alkyl sodium sulfate ester; Alkyl ether sulphate; The benzene sulfonic acid Arrcostab; The alpha-olefin sulphonic acid ester; Uncle or secondary alkyl sulfonate; Alkylphosphonate; Acyl taurate; Sulfosuccinic acid alkyl ester, fatty alkyl sulfoacetate; Alpha-sulfonated fatty acid; Alkyl trimethyl ammonium chloride and ammonium bromide; Dialkyl dimethyl ammonium chloride and ammonium bromide; Alkyl dimethyl amine oxide; Alkyl amido propyl group amine oxide; Alkyl betaine; The alkyl amido CAB; And composition thereof.Preferred surfactant comprises and is selected from following those: alkyl sulfate; Alkyl ether sulphate; The benzene sulfonamide acid esters; The alpha-olefin sulphonic acid ester; Uncle or secondary alkyl sulfonate; Alkyl dimethyl amine oxide; Alkyl betaine; And composition thereof.

[00191] make the composition thickening optional alkanolamide can for, but be not limited to coconut oleoyl amine MEA, coconut oleoyl amine DEA, soy amide DEA, lauramide DEA, oleamide MIPA, stearmide MEA, myristamide MEA, lauramide MEA, decyl amide DEA, castor oil acid amides DEA, myristamide DEA, stearmide DEA, oleamide (oleylamide) DEA, tallow acid amides DEA, lauramide MIPA, tallow acid amides MEA, isostearoyl amine DEA, isostearoyl amine MEA, and composition thereof.Alkanolamide is non-flushing surfactant, and if the change that exists then with a small amount of adding so that the composition thickening.

G.pH

[00192] pH of antimicrobial compositions of the present invention is down about 5 or littler, preferred about 4.5 or littler at 25 ℃.In order to obtain all advantages of the present invention, described pH is less than about 4.Typically, the pH of composition of the present invention is about 2 to less than about 5, is preferably about 2.5 to about 4.5.

[00193] pH of described composition is enough low, makes that at least a portion organic acid is a protonated form.Then, described organic acid has and reduces the ability that surface p H comprises skin pH and do not stimulate this surface so that effective class norwalk virus control to be provided.Described organic acid also can deposit from the teeth outwards with cambium or film, and the opposing flushing is removed so that lasting antivirus action is provided.

[00194] the new unexpected result in order to confirm that antimicrobial compositions of the present invention provides has prepared following embodiment, measures the ability of described composition control gram-positive bacteria and Gram-negative bacteria and control class norwalk virus.The percetage by weight of listing is in an embodiment represented reality or the effective weight of the every kind of composition that exists in composition.As skilled in the art to understand and as described below, become to assign to prepare composition by mixing each.

[00195] in preparation and experimental example, use following method:

(a) the active mensuration of the quick sterilization of antimicrobial product (time is killed (Time Kill)).By the activity of time killing method measurement bactericidal composition, wherein be exposed to the survival rate of tested (challenged) organism of antibacterial tests composition as the function mensuration of time.In this test, under the temperature of regulation, make the aliquot of dilute compositions contact one section official hour with the test bacterium of known population.When the time cycle finishes, the neutralization test composition, it has suppressed the antibacterial activity of composition.Calculate percentage of indigenous bacteria population or log minimizing alternatively.

[00196] common, the time killing method is well known by persons skilled in the art.

[00197] can be at the described composition of test under any concentration of 100% at the most.Wherein the selection of institute's working concentration is determined by the researcher, and suitable concentration is that those skilled in the art measure easily.For example, the thickness sample is tested with 50% dilution usually, and the sample of non-sticky need not dilute.Test specimen is placed the beaker that is equipped with magnetic stirring bar of aseptic 250ml, if desired, make sample volume reach 100ml with aseptic deionized water.All tests are carried out in triplicate, with result combinations, report that average log reduces.

[00198] time of contact section selection also determine by the researcher.Can select any time of contact of section.Be from 15 seconds to 5 minutes typical time of contact, and 30 seconds to 1 minute is preferred time of contact.The contact temperature also can be arbitrary temp, typically is room temperature or about 25 ℃.

[00199] bacterial suspension or test inoculum are to prepare by on any suitable solid culture medium (for example agar) bacterial cultures being grown.Then, wash out bacterial population with stroke-physiological saline solution from agar, the population of regulating this bacterial suspension is to about 10 ⁸Every milliliter of colony-forming units (cfu/ml).

[00200] following table has been listed the test bacterial cultures that uses in this test, and it comprises bacteria name, ATCC (American Type Culture Collection) identification number and the abbreviation of the biological name of use thereafter.Staphylococcus aureus is a gram-positive bacteria, and Escherichia coli, pneumobacillus and Salmonella choleraesuls are Gram-negative bacteria.

Biological name	ATCC#	Abbreviation
			Staphylococcus aureus	6538	S.aureus
Escherichia coli	11229	E.coli
			Pneumobacillus	10031	K.pneum
Salmonella choleraesuls	10708	S.choler

[00201] beaker that will comprise subject composition places water-bath (if expectation constant temperature), or is placed on (if expectation environmental experiment room temperature) on the magnetic stirring apparatus.Then, inoculate sample with the test bacterial suspension of 1.0ml.Stir the time of contact that inoculum is scheduled to this subject composition.When expire time of contact, this subject composition/bacterial mixture of 1.0ml is transferred in the neutralizer solution of 9.0ml.Then, (decimal) that carries out by ten times is diluted to computable scope.For different organisms, dilution factor can be different.Selected dilution is placed on (TSA+ is for containing the tryptic soy agar of lecithin and polysorbate 80 (polysorbate80)) on the TSA+ plate, triplicate.Then, this plate was cultivated 24 ± 2 hours, the colony number of counting survival, and calculate percentage or log minimizing.Measure contrast counting (quantity contrast) by carrying out aforesaid process (difference is to use deionized water to replace subject composition).By the standard microorganism determination method plate count of quantity contrast and sample is changed into cfu/ml respectively.

[00202] using following formula to calculate log reduces.

Log minimizing=log ₁₀(quantity contrast)-log ₁₀(test specimen survival number)

[00203] the following table percentage that demonstrates bacterial population reduces relevant with the log minimizing:

% reduces	Log reduces
		90	1
99	2
		99.9	3
99.99	4
		99.999	5

[00204] (b) antiviral remaining efficacy test

[00205] reference: S.A.Sattar, Standard Test Method for Determiningthe Virus-Eliminating Effectiveness of Liquid Hygienic HandwashAgents Using the Fingerpads of Adult Volunteers, Annual Book of ASTMStandards.Designation E1838-96, incorporate its full content into this paper in the mode of introducing and with reference to ＂ Sattar I ＂; With people such as S.A.Sattar, Chemical Disinfection toInterrupt Transfer of Rhinovirus Type 14 from Environmental Surfaces toHands, Applied and Environmental Microbiology, the 59th volume, the 5th phase, in May, 1993,1579-1585 page or leaf, incorporate its full content into this paper in the mode of introducing, and be referred to as ＂ Sattar II. ＂.

[00206] to measure the used method of antiviral index be improvement to the method for describing in Sattar I in the present invention, and the method for describing in Sattar I is a kind of test that is used for the viricidal activity of liquid hand cleanser (wash type product).Under situation of the present invention, improve this method so that the reliable data for flushing-free type (leave-on) product to be provided.

[00207] improvement of Sattar I comprises and as described below product directly is delivered to skin, virus inoculation thumb pad as described below (fingerpads) and uses ten washing and recycling viruses.Then, by handle the skin part of sterilizing fully and inoculate in described zone with 70% dilution of ethanol in water.

[00208] step:

Test in [00209] ten minute:

[00210] then, the Ethanol Treatment hand with 70%, air-dry.

[00211] test products (typically being 1.0ml to 5.0mL) is applied to hand,, makes its drying except thumb.

[00212] uses about 10 minutes (± 30 seconds), back at product, use feline calicivirus (FVC) (class norwalk virus acceptable substitute (ATCCVR-782, about 1 * 10 of micro-pipette 10 μ l ⁶TCID ₅₀/ 0.1mL (TCID)/ml)) local application is called as a plurality of positions of the appointment skin surface area of thumb pad to hand.At this moment, also the solution of feline calicivirus is applied on the untreated thumb by similar method.

[00213] after during 7-10 minute drying (dry-down), then washs each position 10 times with from each described a plurality of skin part wash-out virus with the eluent (MEM (MEM)+1% green grass or young crops-streptomycin-glutamate) of 1ml.

[00214] then, by with the household bleach of 1:10 (

5.25% clorox) dilution in running water is handled, and follows the skin part of alcohol flushing to sterilize and to inoculate fully with 70%.Using standard technique is sour bacterial plaque method or TCID ₅₀(TCID) measures virus titer.

Test in [00215] one hour:

[00216], allow the experimenter to continue normal activity (except the hand of washing them) at 1 hour to 3 hours time point.After one hour, strict with above-mentioned described for test in 10 minutes, feline calicivirus suspension is applied to the position of appointment on the thumb pad and wash-out from it.

[00217] embodiment 1-11 has confirmed composition of the present invention control virus and bacterium and the ability on formation barrier film on the surface of handling.Embodiment 12-21 has confirmed the ability of described composition control class norwalk virus.Embodiment 22-25 has set forth the other limiting examples of antimicrobial compositions of the present invention.

Embodiment 1

[00218] prepares following composition.

Sample	Composition (wt%)
		A	62% ethanol water
B	30% ethanol water
		C
	2% salicylic acid in 62% ethanol/water
		D
	2% salicylic acid in 30% ethanol/water
		E
	2% salicylic acid in dipropylene glycol/water

[00219] kills the antiviral activity of working sample rhinovirus 1A and rotavirus Wa in the suspension test in the time.Following table has been summed up the result of this test.

[00220] this embodiment has set forth the synergistic corrosion virus effect that the pure and mild log that sterilizes provides less than the combination of 1 organic acid.Sample A and B show that independent sterilization alcohol can not provide acceptable virus control.Sample E shows the virus serotype of salicylic acid this test of deactivation fully that is dissolved in dipropylene glycol and the water.Yet, the virus serotype of fully having eliminated this test as the sample C and the D of composition of the present invention.

Embodiment 2

[00221] preparation can reduce the following antiviral composition of skin pH, and it is applied to the thumb pad of human volunteer:

¹⁾Acrylate/C10-30 alkyl acrylate cross-linked polymer;

²⁾Preservative comprises propane diols, diazonium ureine (diazolidinyl urea), methyl hydroxybenzoate and propylben.

The pH of sample 2 is 3.1.

[00222] in this test, sample 2 is applied to the thumb pad of all fingers of eight volunteers except that thumb.Thumb is the contrast position.The volunteer is divided into four groups, every group two people.At preset time, estimate rhinovirus titre on all thumb pads of every hand that (challenged) respectively organize I-IV to measure the time dependence effect of this subject composition.In the time suitable to each combination, the skin pH that also measures thumb pad is to measure the time course that skin pH replys this subject composition.For each group I-IV, it is respectively 5 minutes, 1 hour, 2 hours and 4 hours to the predetermined test period that rhinovirus is estimated and skin pH measures.Following table has been summed up average log (the rhinovirus titre of inoculum), mean skin pH and the average log (the rhinovirus titre of recovery) from the volunteer's of research test thumb pad that handles by group.

Group	Use the initial pH (on average) in back	The skin pH (on average) of test period	The titre of log[inoculum] (on average)	The titre that log[reclaims] (on average)
					I	3.0	3.0	3.9	0.23
II	2.8	3.4	4.0	0.23
					III	3.0	3.8	3.8	0.23
IV	3.0	3.8	4.3	0.23

[00223] each the group (that is, different time points) data show average recovery the rhinovirus titre less than 1 virion, perhaps be lower than the detection limit of this test.This data declaration after 4 hours the effect of the inventive method, and confirm that further skin pH can eliminate viral challenge effectively fully less than about 4.Citric acid, malic acid and polymeric acid are (promptly

Being combined in 20) provides organic acid residual barrier film on the described thumb pad, it has increased the lasting antiviral activity of said composition.

Embodiment 3

[00224] with following compound treatment test experimenter's clean thumb pad.Before handling, measure the baseline skin pH registration of thumb pad with said composition.Also after drying on the thumb pad, carry out skin pH immediately and measure, after 4 hours, measure once more then in said composition.

Sample	Form (weight %)	Mean skin pH (T=0)	Mean skin pH (T=4 hour)	The Log 10 of virus reduces	Virulent hand %
						A
	2% citric acid, 2% malic acid, 62%ETOH, 1.25% hydroxyethylcellulose	2.81	3.23	>3log 10	0
						B	2% citric acid, 2% tartaric acid, 62%ETOH, 1.25% hydroxyethylcellulose	2.64	3.03	>3log 10	0
C	2% malic acid, 2% tartaric acid, 62%ETOH, 1.25% hydroxyethylcellulose	2.66	2.94	>3log 10	0
						D	62%ETOH, 1.25% hydroxyethylcellulose	5.53	5.13	<0.5log 1-	100
E	2% citric acid, 2% malic acid, 70%ETOH, 1% polyacrylic acid	2.90	3.72	>3log 10	0
						F	70%ETOH, 1% polyacrylic acid	4.80	5.16	2.0log 10	100
G	70%ETOH, 1.25% hydroxyethylcellulose	5.3	5.25	<0.5log 10	100

1) ETOH is an ethanol

[00225] handling thumb pad after 4 hours, be 1.3 * 10 with titre with sample A-G ³The rhinovirus 39 of pfu (plaque forming unit) is applied to thumb pad.Should virus on thumb pad dry 10 minutes, wash this thumb pad with comprising the antibiotic viral recovery meat soup of 75%EBSS and 25%FBS and 1X (viral recovery broth) then.Sample is reclaimed in the meat soup serial dilution and places on the H1-HeLa cell in virus.Measure titre according to plaque assay.The acid-containing composition that use comprises in citric acid, malic acid and the tartaric acid two kinds mixture obtains the complete inactivation of rhinovirus 39, that is, log reduces greater than 3.Hydroxyethylcellulose or polyacrylic having help form more continuous organic acid film or layer on the thumb pad of handling, and it strengthens the lasting antiviral activity of said composition again.

Embodiment 4 antibacterial activities

¹⁾Time of contact on skin

A.62% ethanol, 2% citric acid, 2% malic acid, 1.25% hydroxyethylcellulose

B.62% ethanol, 2% citric acid, 2% malic acid, 1.25% hydroxyethylcellulose and emollient

[00226] this embodiment has illustrated that composition of the present invention also provides fast and broad-spectrum antibacterial activity.

Embodiment 5

[00227] with following compound treatment test experimenter's clean thumb pad.Before handling, measure the baseline skin pH registration of thumb pad with said composition.Also carrying out skin pH immediately in said composition after drying on the thumb pad measures.

[00228] after handling thumb pad, be 1.4 * 10 with titre immediately with said composition ⁴The rhinovirus 14 of pfu (plaque forming unit) is applied to thumb pad.Should virus on thumb pad dry 10 minutes, then, wash this thumb pad with comprising the antibiotic viral recovery meat soup of 75%EBSS and 25%FBS and 1X.Sample is reclaimed in the meat soup serial dilution and places on the H1-HeLa cell in virus.Measure titre according to plaque assay.Complete inactivation with described acid-containing composition acquisition rhinovirus 14 obtains log and reduces 4.

Sample	Form (weight %)	PH value of solution	The Log10 of virus reduces 30 seconds	Virulent hand %
					A
	2% citric acid, 2% malic acid, 70%ETOH, 1% polyacrylic acid	3.10	4log	0

Embodiment 6

[00229] the following composition of preparation is to test organic acid and organic acid blend effect and the antiviral efficacy to skin pH.

Sample	Form (weight %)	Mean skin pH (T=0)	Mean skin pH (T=2 hour)	The Log10 of virus reduces
					A	4% citric acid in 70% ethanol/water	2.97	3.64	>3log 10
B	4% malic acid in 70% ethanol/water	2.91	3.94	>3log 10
					C	2% citric acid in 70% ethanol/water and 2% malic acid	2.99	3.38	>3.log 10
D	4% tartaric acid in 70% ethanol/water	2.56	3.0	>3log 10

[00230] with the described clean thumb pad of testing the experimenter of sample A-D processing.With before the compositions-treated, measure the baseline skin pH registration of thumb pad.Also measure and after two hours, measure once more in carrying out skin pH after the drying on the thumb pad immediately in said composition.

[00231] all sample A-D inhibition skin pH are lower than 4 two hours.The combination of citric acid and malic acid (sample C) was compared the lower pH of the identical acid maintenance of independent (the sample A and B) that uses two hours.4% tartaric acid composition (sample D) demonstrates the inhibition maximum to skin pH.

[00232] with described solution-treated thumb pad after two hours, with rhinovirus 39 with 4 * 10 ⁴The titre of pfu is applied to thumb pad.Should virus on thumb pad dry 10 minutes, then, wash this thumb pad with comprising the antibiotic viral recovery medium of 75%EBSS and 25%FBS and 1X.Sample is reclaimed in the meat soup serial dilution and places on the H1-HeLa cell in virus.Measure titre according to plaque assay.Obtain the complete inactivation of rhinovirus 39, obtain log and reduce greater than 3.

[00233] following embodiment has illustrated that in the presence of alcohol, polymeric acid, particularly acrylate homopolymer or copolymer are given antiviral efficacy.Described polymeric acid has low pH and the direct contact (substantivity) good to skin, and it passes in time and has kept low skin pH effectively and helped the antiviral efficacy that provides lasting.Described polymeric acid also helps to provide continuous substantially organic acid layer or film on the surface of handling, and therefore it increase the lasting antiviral activity of said composition.

[00234] confirmed in the presence of alcohol, used acrylic acid-based polyalcohol to reduce the synergy of skin pH.Yet, under the situation that does not have alcohol, passing in time, acrylic acid-based polyalcohol does not keep skin pH to reduce the degree that reaches identical.Importantly be that when using the combination of polymeric acid and alcohol, skin pH reduces the less pH that depends on composition.The synergy of showing between described polymeric acid and the described alcohol is unexpected, and it provides reduction skin pH the new method of the permanent disease-resistant poison effect so that expectation to be provided for a kind of.

[00235] when acrylic acid-based polyalcohol is used in combination with polycarboxylic acid, also confirmed the synergy of quick and lasting antiviral activity.Discovery utilizes a spot of polymeric acid (about 2% weight of for example about 0.1%-) and polycarboxylic acid such as citric acid, malic acid, tartaric acid and composition thereof can strengthen polycarboxylic antiviral activity together.This synergy allows to reduce polycarboxylic concentration in the antiviral composition and can correspondingly not reduce antiviral efficacy.This reduction of polycarboxylic acid concentration may stimulate the gentle degree that has improved composition by the minimizing composition.(but this paper and do not rely on it) in theory, polymeric acid help to form residual barrier film of organic acid or layer on the surface of handling, and it has increased the lasting antiviral activity of said composition.

Embodiment 7

[00236] preparation comprises polyacrylic acid (1wt%), the i.e. composition of ULTREZ 20 (available from Noveon Europe) in 70% ethanol water and water.Various compositions (1.8ml) are applied to test experimenter's thumb, forefinger and middle finger.Before processing, after two hours, measure skin pH registration after (benchmark), the dry fingers immediately and once more.Mean skin pH registration is summarized as follows.

[00237] initial, polyacrylic acid suppresses skin pH to about 4.5, and after two hours, skin pH remains on below 5.Composition (4.4) the inhibition skin pH that contains ethanol is lower slightly than the composition (4.5) that does not contain ethanol.This result shows when using polyacrylic acid and ethanol has synergy to reducing skin pH.

[00238], after two hours rhinovirus 39 is being applied to 9.8 * 10 with above-mentioned compositions-treated thumb pad ²The thumb pad that the titre of pfu is handled.Should virus on thumb pad dry 10 minutes, then, reclaim this thumb pad of meat soup flushing flushing with virus.To reclaim in the meat soup sample serial dilution and place on the H1-HeLa cell in virus.Measure titre according to plaque assay.Two kinds of compositions all reduce virus titer.Yet the composition that comprises ethanol is to demonstrating the effect of the rhinovirus bigger a little than the composition that does not contain ethanol, and it reduces titre 1.8log, and the composition that does not contain ethanol reduces titre 1.5log.

[00239] this data declaration polyacrylic acid suppresses skin pH generation antiviral efficacy.These data illustrate that also polyacrylic acid and ethanol synergy reduce skin pH, therefore produce the effect of bigger rhinovirus.

[00240] in order to confirm this effect, prepare following eight kinds of compositions, wherein will comprising polyacrylic (contain and do not contain ethanol) solution, to be buffered to pH be about 4.5,5.0,5.5 or 6.0.

Sample	Composition (weight)	PH value of solution	Mean skin pH2 hour	The log of virus 10Reduce
					A	1%ULTREZ 20/70% ethanol	4.54	4.52	>2log 10
B	1%ULTREZ 20/70% ethanol	5.10	4.87	>2log 10
					C	1%ULTREZ 20/70% ethanol	5.54	4.41	>2log 10
D	1%ULTREZ 20/70% second	6.17	4.32	>2log 10

	Alcohol
					E
	1％ULTREZ 20	4.57	4.93	<1log 10
					F	1％ULTREZ 20	5.12	5.46	<1log 10
G	1％ULTREZ 20	5.55	5.33	<1log 10
					H	1％ULTREZ 20	6.32	5.70	<1log 10

[00241] the described eight kinds of compositions of test are to the effect of skin pH and viral effect.Every kind of composition (1.8ml) is applied to test experimenter's thumb, forefinger and middle finger.Before processing, after two hours, measure skin pH registration behind (benchmark), the product drying immediately and once more.

[00242] suppresses skin pH to lower value because of comprising every kind of composition of ethanol than the composition that does not contain ethanol, so skin pH data show goes out polyacrylic acid and the ethanol synergy suppresses skin pH with polyacrylic combination.Comprise ethanol and polyacrylic composition and reduce skin pH to pH4 to 5, irrelevant with the pH of solution.On the contrary, the composition that does not contain ethanol only suppresses the pH to pH5-6 of skin, and final skin pH is similar to the pH of solution.

[00243], after two hours, be 1.7 * 10 with titre in order to test the viral effect of above-mentioned composition ³The rhinovirus of pfu is applied to thumb pad.Should virus dry 10 minutes, wash-out also reclaims serial dilution in the meat soup in virus.Sample is placed on the H1-HeLa cell, and measure virus titer according to the plaque assay method.Comprise ethanol and reduce virus titer greater than 2log, and the compositions display that does not contain ethanol goes out virus titer and reduces less than 1log in conjunction with polyacrylic composition.Therefore, there are synergy in polyacrylic acid and ethanol aspect the skin pH reducing, and it provides the antiviral efficacy of bigger rhinovirus.(but this paper and do not rely on it) in theory, ethanol help to provide organic acid more continuous film or layer on skin, for example, make it average and equably said composition is applied to the surface by the surface tension that reduces composition, particularly on the skin.

Embodiment 8

[00244] prepares the antiviral efficacy that following composition provides with further elaboration polyacrylic acid.

Sample	Composition (wt%) thickener	PH value of solution	2 hours mean skin pH	Virulent hand %
					A
	1% polyacrylic acid	4.21	4.7	63％
					B	5.5%CRODAFOS acid 1)	5.41	5.0	100％

C

1.25％NATROSOL 250 HHR CS 2)

6.32

5.3

100％

¹⁾CRODAFOS CS20 acid is Ceteth-20 ﹠amp; Jing Layingzhichun ﹠amp; DCP; With

²⁾NATROSOL 250 HHR CS are hydroxyethylcellulose.

[00245] sample A-C (1.8ml) is applied to thumb, forefinger and the middle finger of clean hand.Before processing, after four hours, carrying out skin pH registration once more after two hours and for sample C immediately and for sample A and B after (benchmark), the dry fingers.The mean value of skin pH value is provided in the table.

[00246] comprise polyacrylic sample A and reduce skin pH to maximum degree, after two hours, final skin pH is pH4.7.Sample B and sample C do not reduce skin pH to being lower than pH5.0.This data show goes out polyacrylic acid to be had the skin of inhibition pH and keeps low minimum two hours ability of skin pH.

[00247] goes back the viral effect of test specimen A-C rhinovirus 39.With load is about 10 ³The virus of pfu is coated in thumb, forefinger and the middle finger of the hand of each processing, and makes its dry 10 minutes.Then, reclaim meat soup with virus and wash described finger, with the sample serial dilution with place on the H1-HeLa cell.Use plaque assay to measure virus titer.For sample B and C, 100% hand is positive to rhinovirus, and its effect that shows these composition rhinovirus is very little.On the contrary, confirmed the viral effect of sample A, because find that only 63% hand is positive to rhinovirus.

Embodiment 9

[00248] embodiment 7 has confirmed to exist between polyacrylic acid and the ethanol synergy, and it produces and suppresses skin pH and antiviral efficacy.Prepare following composition and make up the effect that resists viral effect with polyacrylic acid and ethanol separately with research polycarboxylic acid blend and independent polycarboxylic acid composition.Preferably comprise minimum organic acid antiviral composition and confirmed lasting antiviral efficacy.

[00249] described composition is applied to the thumb pad of clean hand.After the time of appointment, with about 10 ³To 10 ⁴The rhinovirus 39 of pfu is applied to described hand, and makes its dry 10 minutes.Reclaim virus by reclaim meat soup flushing hand with virus.Then, sample is reclaimed in the meat soup serial dilution and places on the H1-HeLa cell in virus.Measure virus titer with plaque assay.The percentage of the hand that will be positive to rhinovirus is summarized as follows.

Composition (wt%)

Time

Rhinovirus is

		Positive hand %
			70% ethanol	15 minutes	100％
1% citric acid/1% malic acid/10% ethanol/water	1 hour	100％
			1% polyacrylic acid/4% citric acid/70% ethanol/water	4 hours	91％
1% polyacrylic acid/1% citric acid/1% malic acid/70% ethanol/water	4 hours	0％

[00250] composition that comprises 70% independent ethanol is not effective antiviral composition.Citric acid after 1 hour (1%) and malic acid (1%) have been lost the effect of rhinovirus, because find 100% hand rhinovirus are positive.On the contrary, in the time will comprising 1% citric acid and 1% malic acid composition and be applied to hand, do not detecting virus on hand after four hours in conjunction with polyacrylic acid and 70% ethanol.Independent acid (4% citric acid) is less in conjunction with the effect of the combination rhinovirus of polyacrylic acid and ethanol, because find after 4 hours 91% hand rhinovirus is positive.

[00251] this data acknowledgement uses polyacrylic acid and ethanol can make the polycarboxylic acid of low concentration obtain the antiviral efficacy of expectation.This is improved to small part and has formed organic acid residual film or layer due on skin.

Embodiment 10

[00252] in composition, use polyacrylic acid and ethanol to suppress skin pH, as in embodiment 7, confirming to the value that is lower than pH value of solution.To comprise citric acid, malic acid, polyacrylic acid and ethanol antiviral composition and whether can be buffered to higher pH value of solution and provide the skin pH that is equal to or less than pH4 in order to test, prepare following composition to obtain lasting antiviral activity.

Sample	Composition (wt%)	PH value of solution	Initial skin pH	Skin pH after 4 hours	Virus reduces
						A	1%ULTREZ 20/2% citric acid/2% malic acid/70% ethanol	3.2	2.9	3.7	>3log 10
B	1%ULTREZ 20/2% citric acid/2% malic acid/70% ethanol	4.34	3.4	3.7	>3log 10
						C	1%ULTREZ 20/2% citric acid/2% malic acid/70% ethanol	4.65	3.6	3.8	>3log 10

[00253] described composition (1.8ml) is applied to thumb, forefinger and the middle finger of clean hand.Before processing after (benchmark), the dry fingers immediately and after four hours, measure skin pH registration once more.The mean value of skin pH value provides as above.

[00254] the initial skin pH of the skin of handling with sample A-C is suppressed to pH 2.9 to 3.6, and wherein along with pH value of solution reduces, initial skin pH reduces.Yet after four hours, the skin pH of all three kinds of compositions is about pH 3.7.Consistent with the foregoing description, pH value of solution can not be inferred skin pH subsequently.

[00255] goes back the viral effect of test specimen A-C rhinovirus 39.With load is about 10 ³The virus of pfu is coated at the thumb of the hand of each processing, forefinger and middle finger, and makes its dry 10 minutes.Then, reclaim meat soup with virus and wash described finger, with the sample serial dilution and place on the H1-HeLa cell.Use plaque assay to measure virus titer.Be not recovered to virus on hand from arbitrary and show that all three kinds of sample A-C have antiviral efficacy.

[00256] this data acknowledgement is when being used in combination citric acid and malic acid and polyacrylic acid and ethanol in composition, the pH of solution can be buffered to higher, for example be buffered to and be applied to skin milder and safer pH, still keep the ability that suppresses skin pH and demonstrate antiviral activity simultaneously.This result also is retained in organic acid residual layer or film on the skin due to small part after volatile compositions composition evaporation.

[00257] following test confirms that composition of the present invention provides continuous basically organic acid barrier film on the surface of handling.Especially, following test shows that composition of the present invention tolerance washes from the surface of handling, and for example after flushing three times, at least 50% non-volatile composition components (comprising organic acid) is retained on the surface of processing, as spectrometric by NMR and IR.In addition, after flushing 10 times, the non-volatile composition components of effective antiviral amount is retained on the surface of processing, also uses NMR and EIR spectrometry.

[00258] in following test, will comprise 2% malic acid by weight, 2% citric acid, 1% polyacrylic acid, 62% ethanol and 0.5% waterborne compositions (composition A) as the hydroxyethylcellulose of gelling agent compares with the waterborne compositions (composition B) that comprises 2% malic acid, 2% citric acid and 62% ethanol.Described composition is applied on the glass surface so that film to be provided.After each flushing, carry out infrared (IR) and nuclear magnetic resonnance (NMR) spectrum of described film, the composition B that recorded after water washes 1 time fully from the described surface eccysis.Therefore, composition B can not demonstrate resistance to water, and the film or the layer of non-volatile composition components can not be provided from the teeth outwards.

[00259] opposite, IR and NMR spectrum show that composition A provides the washable type film or the layer of composition components on the surface of handling.After beginning to wash three times, the amount that is retained in the lip-deep composition components of processing reduces, and then in the flushing afterwards, its opposing is further removed from the surface of handling.IR and NMR optical spectrum surface light are after 10 water flushings, and detectable and non-volatile composition components effective dose is retained on the surface of processing.

[00260] carries out another test to measure water contact angle from the teeth outwards." contact angle " is the measurement yardstick of the ability on water-wet surface.In this test, be applied to composition A and B on the glass surface and make its drying.Then, do not washing and washing under two kinds of situations, using deionized water to measure the contact angle of the glass surface of handling with composition A and B.Also measurement blank, promptly the contact angle of untreated glass in contrast.Following table has been summed up the result of contact angle test.

	Composition A does not wash	Composition A, flushing	Composition B does not wash	Composition B, flushing	Blank glass
						Average registration (number of degrees)	45.96	72.66	6.69	41.51	38.4 7
The variation of the number of degrees		26.7		34.8
						Rate of change %		58.1		520.2

Described contact angle data show that composition A has improved glass surface, and lasting barrier film or layer is provided on glass surface.These data show that also composition B can be from eccysis on the surface, because contact angle and blank glass is substantially the same behind flushing composition B.

[00261] carries out another and test the residual film absorption metal ion that confirms composition A.In this test, at the film of formation composition A on glass, drying at least 4 hours is exposed to the metal ion solution that contains 0.5M concentration then.Then, with SEM scanning analysis sample.Data in the following table show that film that composition A obtains is effectively in conjunction with the metal ion of several types.(but this paper and do not rely on it) in theory, this is a kind of superficial phenomenon, because it is unknown that metal ion is transported to the mechanism of described film.

Also gathered the reflectivity displaing micro picture (Fig. 1) of the surface coverage that demonstrates composition A and B.Appended displaing micro picture shows that composition A provides basically surface coverage completely, i.e. the covering of composition A on treatment surface is more even, and it provides the continuous basically layer or the film of non-volatile composition components on this surface.Appended displaing micro picture is the digital translation of reflectivity, and it provides the directly related property with surface coverage.This displaing micro picture confirms composition A (figure Ia) and Ib)) film that provides has than (figure Ic) and the same)) adhesion, dispersion and the crystal formation character improved.

Embodiment 11

[00262] time of carrying out with another kind of bacterium is killed the wide spectrum effect that test has confirmed composition of the present invention.In this test, tested following antimicrobial compositions.

Composition	Percetage by weight
		Cetanol	1.00
Glycerine	1.00
		Isopropyl palmitate	1.00
Dimethyl silicone polymer 100 CST	1.02

Ethanol SDA-40B	3.09
		Natrosol 250 HHX	0.26
Deionized water	10.94
		Deionized water	17.65
ULTREZ 10 polymer	1.01
		Ethanol SDA-40B	58.82
Citric acid	2.00
		Malic acid	2.00
Sodium hydroxide 50%	0.22

[00263] under the following conditions, the test above-mentioned composition is controlled the ability of following microorganism.

The test system:	Staphylococcus aureus ATCC6538 Escherichia coli ATCC 11229 bacterium monocytogenes ATCC 7644 enterobacter cloacae ATCC 13047
		Test temperature	Room temperature (20-25 ℃)
Open-assembly time	15 and 30 seconds
		Neutralizer	The neutralizer screening that the D/E medium of 99mL carries out as the part of test has confirmed described neutralizer neutralized product and harmless to the organism of test fully
Subculture medium	D/E agar
		Cultivate	Descend 72 ± 4 hours (for people's Candida albicanss) 35 ± 2 ℃ following 48 ± 4 hours (for staphylococcus aureus, Escherichia coli, bacterium monocytogeneses) under 30 ± 2 ℃ 48 ± 4 hours (for enterobacter cloacae) at 26 ± 2 ℃

[00264] this test data is summarized as follows:

Inoculum quantity (CFU/mL)

The test system	A	B	C
				Staphylococcus aureus ATCC 6538	30 x 10 6	29 x 10 6	3.0 x 10 7
Escherichia coli ATCC 11229	18 x 10 6	18 x 10 6	1.8 x 10 7
				Monocytosis Lee department is (family name) bacterium ATCC 13047 too	26 x 10 6	29 x 10 6	2.8 x 10 7
Enterobacter cloacae ATCC 13047	31 x 10 6	35 x 10 6	3.3 x 10 7

Staphylococcus aureus ATCC 15442

Open-assembly time (second)	Survivor (CFU/ml)	Average survivor (CFU/ml)	Log reduces	Reduce percentage
					15	<100，<100	<100	>5.48	>99.999
30	<100，<100	<100	>5.48	>99.999

Escherichia coli ATCC 11229

Open-assembly time (second)	Survivor (CFU/ml)	Average survivor (CFU/ml)	Log reduces	Reduce percentage
					15	2 x 10 2，<100	<1.5 x 10 2	>5.08	>99.999
30	<100，<100	<100	>5.26	>99.999

Monocytosis Lee department is (family name) bacterium ATCC 7644 too

Open-assembly time (second)	Survivor (CFU/ml)	Average survivor (CFU/ml)	Log reduces	Reduce percentage
					15	<100，3 x 10 2	<2.0 x 10 2	>5.15	>99.999
30	<100，<100	<100	>5.45	>99.999

Enterobacter cloacae ATCC 13027

Open-assembly time (second)	Survivor (CFU/ml)	Average survivor (CFU/ml)	Log reduces	Reduce percentage
					15	＜100, pollute	<100	>5.52	>99.999
30	5 x 10 2，6 x 10 2	5.5 x 10 2	4.78	>99.998

[00265] described data show that the log that compositions display of the present invention goes out at anti-staphylococcus aureus ATCC 6538 of 15 and 30 seconds open-assembly time, Escherichia coli ATCC 11229, monocytosis Lee Salmonella ATCC 7644 and enterobacter cloacae ATCC 13047 reduces about 4 to 5.

Embodiment 12

[00266] comprises the composition of the present invention that active antimicrobial agent is a triclosan by mix following compositions by the percetage by weight of indicating to evenly preparing.

Composition	Percetage by weight
		Triclosan (TCS)	0.15
PEG-9	11.5
		Ethanol	26
Carbopol	0.1
		Citric acid	3
Water	In right amount

[00267] pH of described composition is about 3.5.The saturated percentage of the TCS that composition has is 50%, has good antibacterial properties, kills the log that test demonstrates gram-positive bacteria and Gram-negative bacteria in 30 seconds by the time and reduces greater than 3.Said composition is also eliminated the class norwalk virus on the skin.

Embodiment 13

[00268] to comprise active antimicrobial agent be salicylic another kind of composition of the present invention to evenly preparing by mix following compositions by the percetage by weight indicated.

Composition	Percetage by weight
		Triclosan (TCS)	0.15
PEG-9	11.5
		Ethanol	26
Carbopol	0.1
		Salicylic acid	1
Water	In right amount

[00269] pH of described composition is about 3.5.The saturated percentage of the TCS that said composition has is 50%, has good antibacterial properties, kills the log that test demonstrates gram-positive bacteria and Gram-negative bacteria in 30 seconds by the time and reduces greater than 3.Said composition is also eliminated the class norwalk virus on the human skin.

Embodiment 14

[00270] carries out this and test the effect of killing the virus of measuring the anti-feline calicivirus of composition of the present invention (a kind of substitute of class norwalk virus known in the art).In this embodiment, use following test method and method parameter.

Test method:

[00271] ASTM E 1052-96: be used for the standard test method of effect of the virus of the anti-suspension of antimicrobial

Method parameter:

The test system	Feline calicivirus, F-9 strain, ATCCVR-782
		Organic dirt:	5% hyclone (FBS)
Exposure Temperature	Room temperature (20-26 ℃)
		Open-assembly time	30 seconds
Neutralizer	Use 100% hyclone to reach 10 -2Dilution
		Test medium	MEM (MEM) is supplemented with 5% heat-inactivated FBS, 100 units/ML penicillin, 10 μ g/mL gentamicins, 2.5 μ g/mL amphotericin Bs, 20mM Hepes and 2mM glutamine
The test cell culture	Crandell Reese Feline Kidney (CRFK) cell
		Cultivate	At 35 ± 2 ℃, 5 ± 2%CO 2Following 7 days

[00272] effect of the following four kinds of anti-feline calicivirus of sample of test:

Composition (wt%)	A	B	C	D
					Cetanol	1.00			1.00
Glycerine	1.00			1.00
					Isopropyl palmitate	1.00			1.00
Dimethyl silicone polymer 100 CST	1.02			1.02
					Ethanol SDA-40B	3.09			3.09
Natrosol 250 HHR	0.26			0.26
					Deionized water	10.94	37.94	35.80	10.94
Deionized water	17.65			17.65
					ULTREZ 10 polymer	1.01			1.01
Ethanol SDA-40B	58.82	59.83	60.00	58.82
					Citric acid	2.00	1.01	2.00	2.00
Malic acid	2.00	1.00	2.00	2.00
					Sodium hydroxide 50%	0.22	0.23	0.20	0.22
Total amount	100.00	100.00	100.00	100.00
					pH	3.51	3.54	3.50	3.51

[00273] is used to estimate virucide and must confirms that for (a) this product is can both the described test of complete inactivation under all dilution factors viral based on the result's of EPA general rule; If (b) have cytotoxicity, must confirm to reduce 3-log at least in the titre that surmounts (beyond) cytotoxin level.For all composition A-D, total log reduces owing to the Cytotoxic amount that exists reduces.

[00274] in this test, after 30 seconds open-assembly times, composition A demonstrates the complete inactivation feline calicivirus, and its anti-this virus is effective.Virus titer is reduced to 〉=4.75log ₁₀

[00275] after 30 seconds open-assembly times, composition B demonstrates the deactivation feline calicivirus, and its anti-this virus is effective.Virus titer is reduced to 3.0log ₁₀

[00276] after 30 seconds open-assembly times, composition C demonstrates the complete inactivation feline calicivirus, and its anti-these viruses effectively.Virus titer is reduced to 〉=5.75log ₁₀

[00277] after 30 seconds open-assembly times, composition D demonstrates the complete inactivation feline calicivirus, and its anti-these viruses effectively.Virus titer is reduced to 〉=4.75log ₁₀

Embodiment 15

[00278] carries out the effect that test for the second time confirms the anti-feline calicivirus of antiviral composition of the present invention.In this test, the antiviral activity of composition of the present invention and present commercially available ol-yl (60%) hand gel (hand rub) composition is compared.

[00279] in this test, with composition A and the commercially available alcohols hand gel combination of embodiment 14, promptly ENDURE 450 compares, and it is sold by Ecolab, Inc., Eagan, MN.

[00280] in this test, viral suspension is exposed to the dilution of used test products.Open-assembly time before each is measured, shift out aliquot, by the serial dilution neutralization, and measure the virus that exists.Measure positive-virus contrast, cytotoxicity contrast and neutralization contrast simultaneously.With the concentration of regulation with the time interval is estimated and the antiviral properties of comparative product.

Experimental scheme:

Dilution:	Instant (RTU)
		Virus:	Feline calicivirus, ATCC VR-782, F-9 strain
Open-assembly time	30 seconds, 1 minute and 10 minutes
		Exposure Temperature	Room temperature (25.0 ℃)
Test medium	The test medium that uses in this research is MEM (MEM), is supplemented with 5% heat-inactivated FBS, 10 μ g/mL gentamicins, 100 units/ML penicillin, 2.5 μ g/mL amphotericin Bs
		The designated cell culture	Cat kidney (CRFK)

[00281] in this test, after open-assembly time was 30 seconds, 1 minute and 10 minutes, the titre of virus control was 7.25log ₁₀The viewing test material is 2.5log to the cytotoxicity of composition A and alcohols hand gel ₁₀The neutralization contrast confirms that the neutralization of composition A is≤3.5log ₁₀

[00282] with virus control relatively and consider to confirm the result of neutralization be exposed to feline calicivirus after 30 seconds, 1 minute and 10 minutes, composition A makes virus titer reduce 〉=99.99%.To all three open-assembly times, the log of virus titer reduces 〉=4.0log ₁₀The result who compares and consider to neutralize with virus control confirms be exposed to feline calicivirus after 30 seconds, and described pure hand gel makes virus titer reduce by 82.2%.The log of virus titer is reduced to 0.75log ₁₀The result who compares and consider to neutralize with virus control confirms be exposed to feline calicivirus after 1 minute, and described pure hand gel makes virus titer reduce by 99.7%.The log of virus titer is reduced to 2.5log ₁₀The result who compares and consider to neutralize with virus control confirms be exposed to feline calicivirus after 10 minutes, and described pure hand gel makes virus titer reduce by 99.97%.The log of virus titer is reduced to 3.5log ₁₀

[00283] tests once more to confirm the effect of the anti-class norwalk virus of antiviral composition of the present invention.Embodiment 16 has confirmed the effect after water washes repeatedly, and embodiment 17 has illustrated the barrier properties that composition of the present invention provides.

Embodiment 16

[00284] this embodiment has shown that composition of the present invention is the ability of composition A maintenance effect after the water flushing of embodiment 14.This embodiment confirms that composition A has the ability that forms film on crust, and it can keep antiviral properties after being exposed to the water flushing.This test has been set forth after applied product water flushing several times, and described film deactivation nonenveloped virus is the ability of feline calicivirus (substitute of the class norwalk virus of a kind of Environmental Protection Agency USA approval) for example.

[00285] in this embodiment, one square inch composition A is coated on the glass slide (1 ＂ x, 3 ＂), and in room temperature, makes its drying under promptly about 25 ℃.With each sample of purified rinse water of 5ml and make its drying.Repeat this process to the washing time that reaches standard.The feline calicivirus of ten microlitres is inoculated on the product film, and is expanded to the covering all surfaces.Initial inoculation thing level is 10 ^6.25Total open-assembly time is ten minutes, then, this product that neutralizes, dilution was also cultivated 7 days under 35 ℃.

[00286] result be summarized as follows with Fig. 2 in, show that described antiviral activity can keep through the flushing of 10 water.

The Log of feline calicivirus reduces

Washing time	Sample	1	Sample 2	Mean value	Fmax-mean value
						0	3.5	5	4.3	0.8
1	3.5	3.3	3.4	0.1
					3	3	3.3	3.1	0.1
5	1.3	1	1.1	0.1
					10	1	1	1	0

Embodiment 17

[00287] this embodiment confirms that the composition A of embodiment 14 has the ability that forms film on crust, and described film demonstrates the lasting antiviral properties of deactivation nonenveloped virus feline calicivirus (substitute of the class norwalk virus of a kind of Environmental Protection Agency USA approval).

[00288] in this embodiment, one square inch composition A coating on glass slide (1 ＂ x, 3 ＂), and is at room temperature made its dry preset time.The feline calicivirus of ten microlitres is inoculated on the product film, and is expanded to the covering all surfaces.Initial inoculation thing level is 10 ^6.5(test 1) and 10 ^5.75(test 2).Total open-assembly time is ten minutes (test 1) or 15 minutes (test 2), this product that neutralizes then, dilution and cultivated 7 days down at 35 ℃.

[00289] result is summarized as follows with Fig. 3 a in, shown the ability of barrier film control virus.

The Log of 10 minutes feline calicivirus reduces

Drying time	Sample	1	Sample 2	Mean value	Fmax-mean value
						10min	4.8	3.0	3.9	0.9
1hr	3.0	4.8	3.9	0.9
					4hr	4.5		4.5	0
24hr	3.8	4.0	3.9	0.1
					48hr	3.0	3.3	3.1	0.1

[00290] repeat to select data point, triplicate, and regulate open-assembly time above 15 minutes.To the results are shown among following Fig. 3 b.

The Log of 15 minutes feline calicivirus reduces

Drying time	Sample	1	Sample 2	Sample 3	Mean value	Fmax-mean value
							10min	3.75	4.25	4.25	4.1	0.2
1hr	4	4.25	4	4.1	0.2
						4hr	4.25	4.25	4	4.2	0.1

Embodiment 18

[00291] this embodiment has confirmed the remnants of the anti-feline calicivirus of composition of embodiment 14 effect of killing the virus.

[00292] in this embodiment, by on glass slide, being cut into one inch film of taking advantage of one inch zone to prepare composition A with the glass paper tape of two kinds of thickness (cellophane tape).Arrange described slide, add composition A, make the product intersection pass the product film of slide coherent to set up (even) with the stainless steel scraper.Then, remove described band, make the dry official hour of described film.

[00293] after drying time, the feline calicivirus of ten microlitres is inoculated on the described product film, and launches this film with cell scraper.At room temperature, in the cabinet (cabinet) of bio-safety, cultivate the exposure period of described film regulation.By replace the described product film of virus inoculation to obtain the cytotoxicity contrast with cell culture medium.

[00294] finishes first three ten seconds in exposure period, the cell culture medium of 100 microlitres is added described film, use cell scraper to remove described product film from slide.Use two milliliters hyclone flushing slide and this product that neutralizes.(consider 10 with every kind of sample of sterile glass beads vortex ^-2Dilution), 10 times of serial dilutions of preparation in cell culture medium.

[00295] inoculates the cell of four hole kinds on 24-porocyte culture plate (each hole has comprised one milliliter cell culture medium) with every kind of dilution of 100 microlitres.At 35 ± 2 ℃, 5 ± 2%CO ₂Under cultivated this Tissue Culture Plate seven days.

[00296] is deployed in the virus control that obtains drying on the glass slide by feline calicivirus, and uses the above-mentioned steps test ten microlitres.

[00297] two holes that are inoculated in four holes of diluting separately on the described cytotoxicity plate by the feline calicivirus that will hang down titre confirm the product neutralization.

The test system	Feline calicivirus, F-9 strain, ATCCVR-782
		Organic dirt:	5% hyclone
Exposure Temperature	Room temperature (20-26 ℃)
		Open-assembly time	10 minutes (all drying time), 5 minutes (only 48 hours)
Neutralizer	100% hyclone
		Test medium	MEM (MEM) is supplemented with 5% heat-inactivated FBS, 100 units/mL penicillin, 10 μ g/mL gentamicins, 2.5 μ g/mL amphotericin Bs, 20mM Hepes and 2mM glutamine
The test cell culture	Crandell Reese cat kidney (CRFK) cell
		Cultivate	At 35 ± 2 ℃, 5 ± 2%CO 2Following 7 days

[00298] following result has confirmed the residual activity of composition A.

After [00299] 10 minute: after 10 minutes open-assembly time, reduction 〉=4.75 of the virus titer of feline calicivirus and 3.0log ₁₀

After [00300] 1 hour: after 10 minutes open-assembly time, the virus titer of feline calicivirus be reduced to 3.25 and 〉=4.75log ₁₀

After [00301] 4 hour: after 10 minutes open-assembly time, the virus titer of feline calicivirus is reduced to 4.5log ₁₀

After [00302] 24 hour: after 10 minutes open-assembly time, the virus titer of feline calicivirus be reduced to 3.75 and 〉=4.0log ₁₀

After [00303] 48 hour: for 5 minute exposure time, the virus titer of feline calicivirus is reduced to 3.0 and 3.25log ₁₀For 10 minutes open-assembly time, described virus titer be reduced to 4.25 and 〉=3.25log ₁₀

Embodiment 19

[00304] repeat the test of embodiment 18, but the open-assembly time of using is 15 minutes.Following result has confirmed the residual activity of composition A.

[00305] to composition A, after 10 minutes: after 15 minutes open-assembly time, the virus titer of feline calicivirus reduces by 3.75, 〉=4.25 and 〉=4.25log ₁₀

[00306] composition A, after 1 hour: after 15 minutes open-assembly time, the virus titer of feline calicivirus reduces by 4.0, 〉=4.25 and 4.0log ₁₀

[00307] composition, after 4 hours: after 15 minutes open-assembly time, the virus titer of feline calicivirus reduces 〉=4.25, 〉=4.25 and 4.0log ₁₀

Embodiment 20

[00308] this embodiment has further confirmed the residual effect of the anti-feline calicivirus of composition of embodiment 14.In this embodiment, by on the glass slide of glass paper tape, being cut into one inch film of taking advantage of one inch zone to prepare composition A with two kinds of thickness.Arrange described slide, add composition A, with the stainless steel scraper product is intersected and pass slide to set up coherent product film.Remove described glass paper tape, made described film dry 20 minutes.Use five milliliters MilliQ water to wash the number of times of this film regulation, and make its between flushing dry 20-30 minute.

[00309] after final drying time, the feline calicivirus of ten microlitres is inoculated on the described product film, and launches this film with cell scraper.At room temperature, in the cabinet of bio-safety, cultivate the exposure period of this film regulation.By replace the described product film of virus inoculation to obtain the cytotoxicity contrast with cell culture medium.

[00310] finishes first three ten seconds in exposure period, the cell culture medium of 100 microlitres is added described film, use cell scraper to remove described product film from slide.Use two milliliters hyclone flushing slide and this product that neutralizes.(consider 10 with every kind of sample of sterile glass beads vortex ^-2Dilution), in cell culture medium, carry out 10 times of serial dilutions.

[00311] inoculates the cell of four hole kinds on 24-porocyte culture plate (each hole has comprised one milliliter cell culture medium) with every kind of dilution of 100 microlitres.At 35 ± 2 ℃, 5 ± 2%CO ₂Under cultivated this Tissue Culture Plate seven days.

[00312] is deployed in the virus control for preparing drying on the glass slide by feline calicivirus, and uses the above-mentioned steps test ten microlitres.

[00313] two holes that are inoculated in four holes of diluting respectively on the described cytotoxicity plate by the feline calicivirus that will hang down titre confirm the product neutralization.

The test system	Feline calicivirus, F-9 strain, ATCCVR-782
		Organic dirt:	5% hyclone
Exposure Temperature	Room temperature (20-26 ℃)
		Open-assembly time	10 minutes
Neutralizer	100% hyclone
		Test medium	MEM (MEM) is supplemented with 5% heat-inactivated FBS, 100 units/mL penicillin, 10 μ g/mL gentamicins, 2.5 μ g/mL amphotericin Bs, 20mM Hepes and 2mM glutamine
The test cell culture	Crandell Reese cat kidney (CRFK) cell
		Cultivate	At 35 ± 2 ℃, 5 ± 2% CO 2Following 7 days

[00314] following result has confirmed the residual activity of composition A.

[00315] composition A, 0 flushing back: after 10 minutes open-assembly time, the virus titer of feline calicivirus reduce by 3.5 and 〉=5.0log ₁₀

[00316] composition A, 1 flushing back: after 10 minutes open-assembly time, reduction by 3.5 of the virus titer of feline calicivirus and 3.25log ₁₀

[00317] composition A, 3 flushing backs: after 10 minutes open-assembly time, reduction by 3.0 of the virus titer of feline calicivirus and 3.25log ₁₀

[00318] composition A, 5 flushing backs: after 10 minutes open-assembly time, reduction by 1.25 of the virus titer of feline calicivirus and 1.0log ₁₀

[00319] composition A, 10 flushing backs: after 10 minutes open-assembly time, the virus titer of feline calicivirus reduces 1.0log ₁₀

Embodiment 21

[00320] this embodiment uses adult volunteer's thumb pad to confirm the effect of antimicrobial compositions control class norwalk virus of the present invention.Especially, this embodiment has shown after processing 30 and 60 seconds and 2 hours and 4 hours, and the composition A of embodiment 14 reduces the ability of the level of feline calicivirus ATCC VR-782 on people's thumb pad.

[00321] in this test, 12 experimenters have finished this research.Eight experimenters have finished the research of using the composition A of embodiment 14, and four experimenters have finished the research of using ENDURE 450, and ENDURE is a kind of commercially available alcohol-based disinfectant composition, is sold by Ecolab, Inc., Eagan, MD.Use three thumb pads of every hand of every experimenter to be used for handling a thumb pad of (trial target) and every hand as untreated contrast.The thumb pad of randomization allocation process and untreated contrast thumb pad between eight fingers.A thumb that uses every experimenter is as " input (input) " contrast (counting virus before dry).Two experimenters have finished the neutralizer effect stage of this research.

[00322] for composition A, a male sex and seven female subjects have been finished this research.For ENDURE450, two male sex and two female subjects have been finished this research.Nine experimenters are excluded or withdraw from this research.Four experimenters participate in the adjusting stage (conditioning phase) of neutralization research.Two experimenters (male sex and a women) that meet research standard add and have finished neutralization research.Two experimenters have withdrawed from the neutralization stage of this research.

[00323] use following parametric statistics analysis to come evaluating data.The log of the viral rate of recovery that 12 composition A are handled ₁₀Counting averages.In each period (30 seconds, 60 seconds, 2 hours and 4 hours), obtain the change of untreated counting (15 viral rate of recovery (fifteen viral the recoveries)) mean value of this trial target.Calculate log ₁₀With reduction percentage.

[00324] similarly, to the log of six viral rate of recovery of ENDURE 450 ₁₀Counting averages.In each period (30 seconds, 60 seconds, 2 hours and 4 hours), obtain the change of untreated counting (eight the viral rate of recovery) mean value of this trial target.Calculate log ₁₀With reduction percentage.

[00325] be exposed to described composition after 30 seconds, the titre that composition A demonstrates feline calicivirus reduces above 1.5log, is being exposed to described composition after 60 seconds, and virus titer reduces above 1.9log.Using composition A preliminary treatment after 2 hours and 4 hours, when this virus was used for thumb pad, demonstrating virus titer can reduce above 1.7log.These results have confirmed that after processing the lasting antivirus action of composition A on thumb pad reaches 4 hours.

[00326] be exposed to described product after 30 seconds, the titre reduction that ENDURE 450 compositions display relatively go out the cat family calicivirus surpasses 1.7log and is being exposed to described product after 60 seconds, and virus titer reduces above 2log.With ENDURE 450 preliminary treatments after 2 hours and 4 hours, when virus is applied to thumb pad, demonstrate virus titer reduction much smaller (be 0.17 and be 0.4 at 4 hours) at 2 hours.In a word, these data show that the antiviral persistence of use composition A on the thumb pad of inoculation feline calicivirus is bigger than persistent effect of ENDURE 450.

[00327] this result of the test is summarised among Fig. 4, demonstrates remarkable residual activity through the reduction by 99% of 4 hours composition A.Fig. 4 also comprises the data in literature that demonstrates the straight chain 60% pure disinfectant that does not have residual activity basically.

Embodiment 22-25

	Embodiment 22	Embodiment 23	Embodiment 24	Embodiment 25
					Ethanol SDA 40B 190 Proof	75	85	95	25
Sad		0.05		0.05
					Citric acid	0.5	0.5	1.5	0.5
Malic acid	0.5	0.5	1.5	0.5
					Pluronic F108		0.2	0.2	0.2
Sodium hydroxide or buffer solution	In right amount	In right amount	In right amount	In right amount
					Deionized water
	24	13.75	1.8	73.75
Altogether	100	100	100	100

[00328] all compositions of embodiment 22-25 all are clear, colorless, on being sprayed at table top and when making it dry, stay small amount of residue.

[00329] antimicrobial compositions of the present invention has the final use of some reality, comprises hand cleanser, surgical scrub, wash body fluid (body splashes), bactericide, disinfectant, hand detergent gel, deodorant, dental care additive and similar personal care product.The composition of other type comprises foam compositions, such as mousse etc. and the composition that comprises organic and inorganic filler material such as emulsion, lotion, ointment, cream, paste etc.Described composition further can be used as the antimicrobial that is used for abiotic surface, and described abiotic surface is the sink and the table top of hospital, tourism passenger steamer, sanatorium, catering service zone and meat-packing plant for example.Antimicrobial compositions of the present invention can be prepared into the instant composition or the concentrate (dilution before use) of dilution.

[00330] as discussed above, animate and inanimate surface can the method according to this invention be handled.The surface of particular importance is a mammalian skin, and particularly human skin is used for the propagation of deactivation or termination bacterium and class norwalk virus.Yet method of the present invention also is used to handle all types of abiotic surfaces.

[00331] method of the present invention is useful to treatment of hard surfaces.As used herein about the surface of compositions-treated of the present invention, term " firmly " refers to comprise the surface of refractory material, such as glaze and no glazed ceramic wall tile, brick, porcelain, pottery, metal, glass etc., comprise that also timber and hard plastics are such as formica (formica), polystyrene type plastics, vinyl group of plastics, acrylics, ester plastic etc.Such surface can be found in for example kitchen and bathroom.Crust can be porous or atresia.

[00332] method of the present invention also can be used for the crust in processing facility (such as dairy facilities, wine brewing facility and food processing facility), health-care facilities (such as hospital, clinic, surgery center, dentistry office and laboratory), long-term care facility (such as sanatorium), farm, tourism passenger steamer, school and the private residence.

[00333] method of the present invention can be used for surface ratio such as floor, wall, ceiling and the drainpipe of processing environment.This method can be used for treatment facility such as food processing equipment, dairy equipment, winery equipment etc.Described composition can be used for handling kinds of surface, is included in food, dairy products and brewages food contact surface in the facility, table top, furniture, sink etc.Described method further can be used for handling implement and instrument, comprises that such as medical tool and instrument, dental instruments and instrument and the equipment that uses in health care industry and Inst kitchen cutter, vessel are (such as basin, pot and dish, cutter sweep etc.The method of treatment of hard surfaces is described in United States Patent(USP) Nos. 5,200,189; 5,314,687; With 5,718, in 910, incorporate its full content into this paper by reference.

[00334] except described crust, described method can be used for handling textile such as clothes, protective garment, laboratory clothing, surgery clothes, johnny, carpet, bed, towel, linen etc.

[00335] in use, applying said compositions is with the contact target surface.Described surface can be lived or abiotic.Can by with surface impregnation in composition, the surface immersed die set compound (die composition) or with composition spray, wiping, brushing, foaming, sprinkling, roller, roll to be coated with, to wipe or atomize and come applying said compositions from the teeth outwards.Described composition can manually be used, operative installations is used such as sprayer, foaming machine etc. such as spray bottle or equipment.Described composition also can be used for the inside of machine such as article washing (warewashing) machine or washing machine.

[00336] treatable abiotic surface includes, but are not limited to be exposed to the surface ratio of environment such as desk, floor, wall; Kitchen utensils comprise basin, pot, cutter, fork, spoon and dish; Food boiling and preparation surface comprise dish; The food preparation device; With groove, drum, pipeline, pump, water pipe and other processing unit (plant).A kind of useful applications of described composition is to be applied to the Dairy Processing device, and it is that raw material is made by glass or stainless steel usually.Such device can find at the dairy farm equipment that is used for milk, cheese, ice cream and the processing of other dairy products with at the Dairy Processing plant.

[00337] method of the present invention also can be used for preparing beverage, comprises fruit juice, dairy products, malt beverage, bottled water product, teas and soft drink.Described method can be used for handling used pump, pipeline, groove and mixing arrangement in preparing such beverage.Method of the present invention also can be used for handling air cleaner.

[00338] method of the present invention also can be used for handling vehicle for medical use, medical case (cage) and other medicine equipment, equipment and device.The example of the accessible Medical Devices of method of the present invention is disclosed in U.S. Patent No. 6,632, in 291, is incorporated by reference this paper.

[00339], can use hand pump type or pressurised aerosol injector for domestic. applications.Also described composition can be applied to coating or handle material such as gauze, fiber or non-fiber mesh material, swab, flexible plastic, textile, timber etc.Usually, use is given the antiviral properties of prolongation by described composition being applied to described lip-deep coating process to hard porous or non-porous surface.Also described composition can be joined in the Web materials so that the antimicrobial Wiping articles to be provided.This Wiping articles lived or abiotic surface that can be used for sterilizing.

[00340] antimicrobial compositions of the present invention can be formulated into the multiple product form, comprises liquid, gel and semisolid.Described fluid product can be solution, dispersion liquid, emulsion or similar products like form.Gel and soft solid product form can be transparent or opaque, and it is designed to be used by for example clavate distributor (stick dispenser) or finger.Antimicrobial compositions of the present invention can be prepared into the instant composition or the concentrate (dilution before use) of dilution.

[00341] a kind of certain products form is the liquid or solid composition that is distributed in the water miscible parcel.Described parcel can be joined in an amount of water, when parcel dissolves, discharge composition.Described water miscible parcel typically comprises polyvinyl alcohol.A kind of water miscible parcel of form is disclosed in U.S. Patent No. 5,316, in 688, is incorporated by reference this paper.A large amount of other water miscible parcels are well known by persons skilled in the art, for example are disclosed in United States Patent(USP) Nos. 5,070,126; 6,608,121 and 6,787,512; U.S. Patent Publication No.2002/0182348; Among WO 01/79417 and the European patent Nos.0444230,1 158 016,1,180 536 and 1 251 147, all incorporate this paper by reference into every piece.Capsule is another kind of relevant and useful product form.

[00342] another kind of product form is that described composition is joined absorbent or adsorbing agent carrier such as in polymer particle or the inorganic particle.The carrier of load uses by original state, perhaps adds in other products form liquid, gel, semisolid or the solid.

[00343] another kind of product form is Web materials or the swab that comprises antimicrobial compositions.Then, by said composition being applied to skin with the Web materials wipe surfaces that comprises described composition.

[00344] another kind of product form is goods, and such as latex glove, it has and is applied to or imbeds composition in these goods.During use, described composition is given the surperficial antiviral activity of goods itself or goods contact.Other goods that can have the active compound of imbedding wherein are plastic cup, packaging for foodstuff and plastic containers.

[00345] therefore, the antimicrobial compositions of the present invention that the present invention includes effective dose is applied on the abiotic surface, such as family surface for example table top, surface, kitchen, food preparation surface (chopping block, dish, basin and pot etc.); Principal home front yard apparatus, for example refrigerator, refrigerator, washing machine, automatic dryer, baking oven, micro-wave oven and dish-washing machine; Cabinet; Wall; The floor; Bathroom surfaces, shower curtain, dustbin and/or returnable (recycling bins) etc.

[00346] in one embodiment of the invention, suffering from people that the class norwalk virus infects maybe may be exposed to other people that suffer from the individuality that class norwalk viruses infect and can be administered to antimicrobial compositions of the present invention on hand his or her.The application kills on hand the bacterium that exists and the deactivation class norwalk virus particle on it.No matter the composition of being used is eccysis or it is retained on hand, lasting antiviral activity all preferably is provided.Therefore, the class norwalk virus can not propagate into the individuality that does not infect via hand to the propagation of hand.Use composition amount, frequency of administration and operating period will according to the sterilisation level of expectation for example microbial contamination and/or the skin degree of making dirty change.

[00347] antimicrobial compositions of the present invention is provided at the advantage that wide spectrum in short time of contact kills gram-positive bacteria and Gram-negative bacteria and the control of class norwalk virus.In view of 15 to 60 seconds time range of normal use sterilization skin and abiotic surface, short time of contact is very important with the log of abundant reduction bacterium.Described composition preferably gives contact-making surface lasting antiviral activity.

[00348] composition of the present invention is with short onset time of contact, this is to provide synergy because the pH of composition reduces with the pure and mild organic acid combination of sterilization, and because on the residual barrier film of the volatile component evaporation back of described composition composition components or film be retained in and increased lasting activity on the skin.

[00349] in the embodiment that comprises optional active antimicrobial agent, composition of the present invention is further effective in short time of contact, this is that described antimicrobial is present in the water-based continuous phase neutralization of composition of the present invention because the pH of composition reduces because different with the micella of surfactant.Therefore, described antimicrobial can be used for beginning to reduce bacterial population immediately, and further can be used for being deposited on the skin so that lasting antimicrobial efficacy to be provided.In addition, because it is opposite with surfactant micella, described antimicrobial is in solution, the absolute quantity of antimicrobial in composition can reduce and can influence effect sharply, and before its antimicrobial function of performance, can not remove this antimicrobial from the eccysis of skin upper punch with surfactant.

[00350] obvious, do not deviating under its spirit and scope, therefore of the present invention many modifications and the variation that can set forth as mentioned, have only as the pointed ability of appended claims as qualification of the present invention.

Claims (62)

1. one kind is reduced the method that class norwalk virus population is gone up on the surface, and it comprises that making this surface contact 30 seconds with composition is reduced at least 3 with the log that obtains anti-class norwalk virus,

Described composition comprises:

(a) about 25% sterilization alcohol to about 95% weight;

(b) the kill the virus organic acid of effective dose;

(c) about 0% active antimicrobial agent to about 5% weight;

(d) 0% gelling agent to about 5% weight; With

(e) water,

Wherein the pH of said composition under 25 ℃ is about 5 or littler.

2. the process of claim 1 wherein that described composition forms on described surface comprises the organic acid barrier film.

3. the process of claim 1 wherein and on described surface, form the layer that comprises that organic acid is continuous substantially.

4. the process of claim 1 wherein that described class norwalk virus comprises GI, GII or GIV genome.

5. the method for claim 1, it further comprises from the described composition of described surface flushing.

6. the process of claim 1 wherein and allow described composition to keep from the teeth outwards and drying.

7. the process of claim 1 wherein that described surface is a mammalian skin.

8. the method for claim 7, wherein after drying on the skin, described composition is reduced to less than 4 the pH of skin.

9. the process of claim 1 wherein that described surface is abiotic surface.

10. the method for claim 9, wherein said abiotic surface is a food contacting surface.

11. the process of claim 1 wherein that described composition gives lasting anti-class norwalk virus activity to described surface.

12. the process of claim 1 wherein that the amount of described sterilization alcohol in composition is about 30% to about 75% weight.

13. the process of claim 1 wherein that described sterilization alcohol is C _1-6Alcohol or its mixture.

14. the process of claim 1 wherein that described sterilization alcohol is selected from methyl alcohol, ethanol, isopropyl alcohol, n-butanol, normal propyl alcohol and composition thereof.

15. the process of claim 1 wherein that described composition comprises about 0.05% organic acid to about 15% weight.

16. the process of claim 1 wherein that organic acid in the described composition has the log P less than 1.

17. the process of claim 1 wherein that organic acid in the described composition has 1 or bigger log P.

18. the process of claim 1 wherein that described organic acid comprises that log P is 1 or the second bigger organic acid less than 1 first organic acid and log P.

19. the process of claim 1 wherein water-soluble be at least about 0.05% weight of described organic acid under 25 ℃.

20. the process of claim 1 wherein that described organic acid comprises monocarboxylic acid, polycarboxylic acid, polymeric acid, its acid anhydrides or its mixture with a plurality of carboxyls, phosphate radical, sulfonate radical and/or sulfate radical part.

21. the process of claim 1 wherein that described organic acid comprises having structure RCO ₂The monocarboxylic acid of H, wherein R is C _1-10Alkyl, hydroxyl C _1-3Alkyl, halo C _1-3The phenyl of alkyl, phenyl or replacement.

22. the method for claim 20, wherein said monocarboxylic acid be selected from acetate, propionic acid, sad, glycolic acid, lactic acid, benzoic acid, phenylacetic acid, phenoxyacetic acid, zimanic acid, 2-, 3-or 4-hydroxybenzoic acid, the benzoyl amino acid that contracts, neighbour-,-or right-chlorobenzene acetic acid, neighbour-,-or right-tomatotone and composition thereof.

23. the process of claim 1 wherein that described organic acid comprises contains two to four hydroxy-acid groups and randomly contains one or more hydroxyls, amino or both polycarboxylic acids.

24. the method for claim 23, wherein said polycarboxylic acid is selected from malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, decanedioic acid, fumaric acid, maleic acid, tartaric acid, malic acid, maleic acid, citric acid, aconitic acid and composition thereof.

25. the process of claim 1 wherein that described organic acid comprises that molecular weight is about 500 to about 10,000, the polymeric acid of 000g/mol.

26. the method for claim 20, wherein said polymeric acid are water miscible or water-dispersible.

27. the method for claim 25, wherein said polymeric acid are selected from polymerization of carboxylic acid, polymerization sulfonic acid, sulfated polymers, polymer phosphate and composition thereof.

28. the method for claim 20, wherein said polymeric acid comprises acrylic acid homopolymers or copolymer.

29. the process of claim 1 wherein that described organic acid comprises polycarboxylic acid anhydrides.

30. the method for claim 20, wherein said organic acid comprises polycarboxylic acid and polymerization of carboxylic acid.

31. the method for claim 30, wherein said polycarboxylic acid comprise citric acid, malic acid, tartaric acid or its mixture, and described polymerization of carboxylic acid comprises the homopolymers or the copolymer of acrylic or methacrylic acid.

32. the method for claim 31, wherein said polymeric acid comprises acrylic acid homopolymers or copolymer.

33. the process of claim 1 wherein that described composition comprises about 0.01 active antimicrobial agent to about 2% weight.

34. comprising, the method for claim 33, wherein said active antimicrobial agent be selected from following phenols antimicrobial:

(a) have the 2-hydroxydiphenyl compounds of following structure:

Wherein Y is a chlorine or bromine, and Z is SO ₃H, NO ₂Or C ₁-C ₄Alkyl, r are 0 to 3, and o is 0 to 3, and p is 0 or 1, m be 0 or 1 and n be 0 or 1;

(b) have the phenol derivatives of following structure:

R wherein ₁Be hydrogen, hydroxyl, C ₁-C ₄Alkyl, chlorine, nitro, phenyl or benzoyl, R ₂Be hydrogen, hydroxyl, C ₁-C ₆Alkyl or halogen, R ₃Be hydrogen, C ₁-C ₆The sulphur of alkyl, hydroxyl, chlorine, nitro or alkali metal salts or ammonium salt form, R ₄Be hydrogen or methyl, and R ₅Be hydrogen or nitro;

(c) have the diphenyl compounds of following structure:

Wherein X is sulphur or methylene group, R ₆And R ' ₆Be hydroxyl, and R ₇, R ' ₇, R ₈, R ' ₈, R ₉, R ' ₉, R ₁₀And R ' ₁₀Be hydrogen or halogen independently of each other; With

(d) its mixture.

35. the method for claim 33, wherein said antimicrobial comprise triclosan, to chloro-meta-xylene phenol, hydrogen peroxide, benzoyl peroxide, phenmethylol, quaternary ammonium compound or its mixture.

36. the method for claim 33, wherein when when measuring down for 25 ℃, the amount of described antimicrobial in composition is at least 50% of saturated concentration.

37. the method for claim 36, the amount of wherein said antimicrobial are at least 75% of saturated concentration.

38. the method for claim 37, the amount of wherein said antimicrobial are at least 95% of saturated concentration.

39. the process of claim 1 wherein that the amount of described gelling agent in composition is about 0.1% to about 3% weight.

40. the method for claim 39, wherein said gelling agent comprises natural gum, synthetic polymer, clay, oil, wax and composition thereof.

41. the method for claim 39, wherein said gelling agent are selected from cellulose, cellulose derivatives, guar gum, guar derivative, marine alga, marine alga derivative, water-insoluble C ₈-C ₂₀Alcohol, carrageenan, montmorillonitic clay, poly quaternary ammonium compound and composition thereof.

42. the process of claim 1 wherein that described composition does not contain surfactant.

43. the process of claim 1 wherein that described composition further comprises about 0.1% surfactant to about 15% weight.

44. the method for claim 44, wherein said surfactant comprise anion, cation, nonionic or amphoteric surfactant or its mixture.

45. the process of claim 1 wherein that the pH of described composition is about 2 to less than about 5.

46. the process of claim 1 wherein that described composition comprises that further content is about 0.1% hydrotropic agent to about 30% weight.

47. the process of claim 1 wherein that described composition further comprises about 0.1% polyhydroxyl solvents to about 50% weight, it is selected from dihydroxylic alcohols, trihydroxylic alcohol and composition thereof.

48. the method for claim 7, wherein with after described composition contacts about four hours, the log of the anti-class norwalk virus of described skin is reduced at least 2.

49. the method for claim 7, wherein with after described composition contacts about eight hours, the log of the anti-class norwalk virus of described skin is reduced at least 2.

50. the method for claim 8, wherein the contact after 4 hours, the skin pH of mammal skin is less than 4.

51. the process of claim 1 wherein and before described surface is exposed to the class norwalk virus, described composition is applied to this surface.

52. the process of claim 1 wherein within twenty four hours repeatedly applying said compositions.

53. the method for claim 2, wherein after water flushing 10 times, the organic acid of effective dose is retained in the lip-deep barrier film.

54. the method for claim 1, it is after water flushing three times, and the nonvolatile element of the described composition of at least 50% weight is present on the surface.

55. the method for deactivation class norwalk virus and kill bacteria, it comprises the lived or abiotic surface that composition is locally applied to the such processing of needs, and described composition comprises:

(a) about 25% sterilization alcohol to about 95% weight;

(b) the kill the virus organic acid of effective dose;

(c) about 0 active antimicrobial agent to about 5% weight;

(d) 0% gelling agent to about 5% weight; With

(e) water,

Wherein the pH of said composition under 25 ℃ is about 5 or littler.

56. the method for claim 55 wherein gives described surface lasting anti-class norwalk virus effect.

57. the method for claim 55, wherein said class norwalk virus were inactivated about at the most six hours.

58. a method of protecting individual anti-class norwalk virus to infect, it comprises to this individual hand uses the composition that its amount is enough eliminated the class norwalk virus,

Described composition comprises:

(a) about 25% sterilization alcohol to about 95% weight;

(b) the kill the virus organic acid of effective dose;

(c) about 0% active antimicrobial agent to about 5% weight;

(d) 0% gelling agent to about 5% weight; With

(e) water,

Wherein the pH of said composition under 25 ℃ is about 5 or littler.

59. the method for claim 58, wherein applying said compositions before individuality is exposed to the class norwalk virus.

60. the method for claim 58, wherein applying said compositions repeatedly within twenty four hours.

61. the method for claim 58 is wherein from washing described composition on hand.

62. the method for claim 58 wherein allows described composition dries and is retained on hand.

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