CN101466265A - Alcohol-containing antimicrobial compositions having improved efficacy - Google Patents

Abstract

Antimicrobial compositions having a rapid antiviral and antibacterial Effectiveness, and a persistent antiviral effectiveness, are disclosed. The antimicrobial compositions contain (a) a disinfecting alcohol, (b) a blend containing a C12 to C22 alcohol and an ethoxylated C12 to C22 alcohol, such as a cetearyl alcohol and cetereth-20 blend, a cetearyl alcohol, steareth-20, and steareth-10 blend, or a mixture thereof, (c) an optional organic acid and (c) water.

Description

Has containing of improvement effect of pure antimicrobial compositions

The cross reference of related application

[0001] the application requires the rights and interests of the U.S. Provisional Patent Application 60/809,4955 submitted on May 31st, 2006 and the rights and interests of the U.S. Provisional Patent Application 60/811,354 submitted on June 6th, 2006.

Invention field

[0002] the present invention relates to the improved antimicrobial compositions that contains alcohol, it has the anti-bacterial effect of quick and lasting antiviral effect and quick wide spectrum.More particularly, the present invention relates to comprise following antimicrobial compositions: (a) sterilization alcohol, (b) contain C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, for example cetearyl alcohol pure and mild ceteareth-20 blend and (c) optional organic acid.(a) and (b) and coupling (c) can reduce Gram-negative and Gram-positive bacteria, and make virally inactivated or elimination virus, and for example rhinovirus and rotavirus improve sterilization alcohol simultaneously in the lip-deep retention time length of handle.Said composition can be cut down virus population and Gram-negative and Gram-positive bacteria population significantly within one minute.In containing some embodiments of organic acid, composition can provide organic acid barrier layer or film on the processing surface, thereby gives the surface lasting antiviral activity.

Background of invention

[0003] health is subjected to the various microbiological effects that run into every day.Especially, contact with various microorganisms in the environment that can cause may very serious disease in mammal.For example, microbial contamination can cause various diseases, includes but not limited to: food poisoning, streptococcal infection, anthrax (skin), the ringworm of the foot, herpes labialis, conjunctivitis (" blood-shot eye illness "), Coxsackie virus (hand-foot-mouth syndrome), croup, diphtheria (skin), Ebola hemorrhagic fever and impetigo.

[0004] known washing body part (for example washing one's hands) and crust (for example table top and tank) can reduce microbial population significantly, comprise pathogene.Therefore, it is to remove first pipe protection of this pathogene from these surfaces that cleaning skin and other life and inanimate surfaces reduce microbial population, and makes the danger of infection reduce to minimum thus.

[0005] virus is the pathogen type that relates generally to.Virus infections is the most important reason of human morbidity, according to estimates, in developed country, 60% or the acute attack of more human diseases be the result of virus infections.In addition, virus infects every kind of organism of natural world in fact, comprises that all mammals the viral infection rate that takes place among people, pet, domestic animal and the zoo animal is very high.

[0006] virus is demonstrating otherness widely aspect structure and the life cycle.Virus family, their structure, life cycle and virus infections pattern are described in detail in to be discussed in following: Fundamental Virology, 4th Ed., Eds.Knipe ﹠amp; Howley, LippincottWilliams ﹠amp; Wilkins, Philadelphia, PA, 2001.

[0007] briefly, virion is intrinsic obligate parasite, and take place to develop transmitting genetic material between cell, and the enough information of encoding is to guarantee their breeding.In the most basic form, virus is made up of the little nucleotide fragments that is packaged in the simple protein housing.Main difference between the virus is coating and nonenveloped virus, promptly contains or do not contain those viruses of bilayer lipid membrane respectively.

[0008] virus is only bred in living cells.The major obstacle that virus runs into is to obtain to enter intracellular access road, and cell is subjected to the protection of the cell membrane that thickness can be equal to viral size.In order to infiltrate cell, virus at first must be attached to cell surface.Virus is that for a large amount of selectivitys of some cell type it has the ability that is attached to the specific cells surface.Be host cells infected, it is important contacting for virus lastingly, and virus and the interactional ability of cell surface are the attributes of virus and host cell.Virus and the fusion of host cell membrane make intact virion or in some cases only its infectious nucleic acid enter cell.Therefore,, importantly kill the virus of contact skin fast, and lasting antiviral activity is provided on skin or stiff dough ideally, so that the control virus infections in order to control virus infections.

[0009] for example, known that rhinovirus, influenza virus and adenovirus can cause respiratory tract infection.Known that rhinovirus can cause respiratory tract infection.Rhinovirus is the member of picornavirus family, and it is the family that lacks " naked virus " of adventitia.So the appellation human rhinovirus is because they adapt to the nasopharynx district especially, and is the most important pathogene of common cold among adult and the children.State formally that according to official 102 kinds of rhinovirus serotypes are arranged.The most of picornavirus that separates from the human respiratory system is unsettled to acid, and this lability has become rhinoviral defined feature.

[0010] rhinovirus infection by directly contacting with the respiratory secretions of viral pollution in interpersonal propagation.Typically, this contact is the direct contact form with contaminated surface, rather than by sucking airborne virion.

[0011] after initial the pollution, rhinovirus can survive many hours on environmental surfaces, if wipe one's eyes or contact schneiderian membrane with the finger that just pollutes, infects contacting with finger by finger easily and propagating with pointing to contact by contaminated environment is surperficial.Therefore, the skin and the environmental surfaces of viral pollution should be reduced to minimum, thereby reduce the danger of transmission of infection being given the general population.

[0012] some gastrointestinal infections are also caused by virus, for example rotavirus.For example, Norwalk virus causes feeling sick, vomits (often with diarrhoea) and gastrospasm.This infection typically by directly contacting in interpersonal propagation.The acute hepatitis A virus infections can be similarly by a infected with the hand to hand between the immune body, hand do not spread to the direct contact of mouth or droplet transfer mode, or when the individuality that does not infect contacts the solid objects of hepatitis A virus pollution, spread by mediate contact.Many other virus infectionses also are to spread similarly.By making virally inactivated or removing virus removal, can reduce the danger of propagating this virus infections significantly from hand and other environmental surfaces.

[0013] Chang Yong family's phenol/pure disinfectant is effectively for giving the environmental surfaces sterilization of polluting, but lacks lasting viricidal activity.Wash one's hands and to give the finger that pollutes sterilization efficiently, but also lack lasting activity.The explanation of these shortcomings needs to improve viricidal composition, and for example rhinovirus and rotavirus have lasting activity at virus to make it.

[0014] antimicrobial personal care composition is known in this area.Especially, antibiotic Cleasing compositions, hand, arm and face that it typically is used for cleaning skin and eliminates the bacterium that exists on the skin, especially user are well-known commercial products.

[0015] antibacterial compositions is used in for example nursing industry, food service industry, meat industry and private sector by the individual consumer.The extensive use of bactericidal composition has shown that the consumer places critical role to bacterial population on the control skin.The bactericidal composition of example will provide the quick reduction of the substantial and broad spectrum activity of bacterial population, and the adverse side effect relevant with toxicity and skin irritation not.This bactericidal composition is disclosed in U.S. Pat 6,107, and in 261 and 6,136,771, this paper is incorporated herein by reference each.

[0016] one class antibacterium personal care composition is the hand sanitizer.This based composition mainly is that the medical worker uses for hand and finger sterilization.Hand is applied to sanitizer and rubs and enters in hand and the finger, and composition is evaporated from skin.

[0017] hand contains a high proportion of alcohol, for example ethanol with sanitizer.The alcohol of high percentage is present in the composition, and alcohol itself serves as disinfectant.Yet pure rapid evaporation can avoid wiping or flushing hand with the handled skin of sanitizer, has also cancelled any durable antimicrobial activity.Therefore, contain at high proportion alcohol, promptly about 40% of composition weight or bigger, hand can not provide lasting bacteria inactivation with sanitizer.

[0018] anti-bacterial cleaning composition typically is included in active antibacterial agent, surfactant and various other component in water and/or the alcohol carrier, for example dyestuff, spices, pH value conditioning agent, thickener, skin conditioning agent or the like.Some different classes of antibacterial agents have been used for anti-bacterial cleaning composition.The example of antibacterial agent comprises biguanides (for example Chlorhexidine digluconate), diphenyl compounds, phenmethylol, three halogenated diphenyl ureas, quaternary ammonium compound, ethoxylation phenol and phenolic compound, the phenolic compound that replaces of halogen for example, for example PCMX (promptly between chloro--xylenols) and triclosan (promptly 2,4,4 '-three chloro-2 '-dihydroxy diphenyl ether).Demonstrate from the antibacterial activity of low paramount wide region based on the antimicrobial compositions of this antibacterial agent, this depends on the microorganism controlled and concrete antibacterial compositions.Most of commercial antibacterial compositions provides usually and is low to moderate medium antibacterial activity, and does not report antiviral activity.

[0019] logarithm of the microbial population that provides with antimicrobial compositions reduces or percentage reduces and evaluates antimicrobial acivity.It is preferred that the 1-3 logarithm reduces, and it is most preferred that the logarithm of 3-5 reduces, and is least preferred and reduce less than 1 logarithm, for concrete time of contact, usually from 15 seconds to 5 minute.Thus, highly preferred antimicrobial compositions has demonstrated the logarithm minimizing of 3-5 to broad-spectrum micro-organisms in short time of contact.

[0020] viral control ratio bacterial control is more difficult.By abundant reduction bacterial population, risk of bacterial infections can be reduced to acceptable degree.Therefore, the antibacterium deactivation is a target fast.Yet with regard to virus, not only quick inactivating is a target, and needs lasting antiviral activity.This species diversity is to be not enough to reduce infection because only reduce virus numbers.In theory, single virus can cause infection.Therefore, for effective antiviral composition, need or expect complete and lasting basically antiviral activity at least.

[0021] WO 98/01110 discloses the composition that comprises triclosan, surfactant, solvent, chelating agent, thickener, buffer and water.WO 98/01110 relates to use reduction schedule of quantities surface-active agent and reduces skin irritation.

[0022] U.S. Pat 5,635, and 462 disclose the composition that comprises PCMX and selected surfactant.Disclosed therein composition does not contain anion surfactant and nonionic surface active agent.

[0023] EP 0 505 935 discloses and has contained PCMX and nonionic and anion surfactant, especially non-ionic block copolymer surfactant, the composition of combination.

[0024] WO 95/32705 discloses gentle combinations-of surfactants, its can with antibacterium compound for example triclosan combine.

[0025] WO 95/09605 discloses the antibacterial compositions that contains anion surfactant and alkyl poly glucoside surfactant.

[0026] WO 98/55096 discloses the antimicrobial cleaning piece with porous sheet, porous sheet floods with antibacterial compositions, antibacterial compositions contains active antimicrobial agent, anion surfactant, acid and water, and wherein composition has about 3.0 to about 6.0 pH value.

[0027] people such as N.A.Allawala, J.Amer.Pharm.Assoc.--Sci.Ed., Vol.XLII, no.5, pp.267-275 (1953) has discussed the antibacterial activity of active antibacterial agent and combinations-of surfactants.

[0028] A.G.Mitchell, J.Pharm.Pharmacol., Vol.16, pp.533-537 (1964) discloses the composition that contains PCMX and nonionic surface active agent that demonstrates antibacterial activity.

[0029] U.S. Pat 6,110, and 908 disclose a kind of topical germicide, and it contains C2-3 alcohol, free fatty acid and 2-mercaptopyridine zinc oxide.

[0030] U.S. Pat 5,776, and 430 disclose a kind of topical anti-microbial cleaning agent, and it contains Chlorhexidine and alcohol.Said composition contains the denatured alcohol of about 50% to 60% weight and the Chlorhexidine of about 0.65% to 0.85% weight.Said composition is applied to skin, is rubbed in the skin, rinse out from skin then.

[0031] european patent application 0 604 848 discloses a kind of gel-type hand disinfectant, and its pure and mild gross weight that contains antimicrobial, 40% to 90% weight is no more than the polymer and the thickener of 3% weight.The gel friction enters in the hand, and evaporation, to sterilize to hand.The composition of the disclosure usually can not provide sanitized immediately, and lasting anti-microbial effect can not be provided.

[0032] common, hand typically contains with the disinfecting gel: (a) for example coupling of ethanol and isopropyl alcohol of at least 60% weight ethanol or lower alcohol, (b) water, (c) gel polymer, for example crosslinked polyacrylate material, (d) other component, for example skin conditioning agent, spices, or the like.The user can use hand to sterilize to hand effectively with the sanitizer gel by following manner, promptly without soap and water washing, or after with soap and water washing, by on watch face, wiping hand disinfecting gel.Existing commercial hand in order to sterilize and evaporation depends on high-caliber alcohol, and has defective with the disinfecting gel thus.Specifically, because the volatility of ethanol, after the use, main antimicrobial can not be retained on the skin, can not provide lasting anti-microbial effect thus.

[0033] under determining alcohol is lower than 60% condition, do not think that ethanol can be used as bactericide.Thus, in the composition that contains less than 60% alcohol, there is extra Antimicrobe compound, so that antimicrobial acivity to be provided.Yet, the previous open problem which kind of composition component in such antimicrobial compositions can provide control of microorganisms that is not illustrated in.Therefore, for the preparation of the determining alcohol that contains reduction, be difficult for the selection that not only can provide quick antimicrobial result but also have an antimicrobial of lasting antimicrobial benefit.

[0034] U.S. Pat 6,107, and 261 and 6,136,771 disclose the efficient antibacterial compositions that contains the phenols antimicrobial.These patent disclosures solve the composition of problem of bacteria on control skin and the stiff dough, but how record does not control virus.

[0035] U.S. Pat 5,968, and 539,6,106,851 and 6,113,933 disclose the antibacterial compositions with pH value of about 3 to about 6.Said composition contains antibacterial agent, anion surfactant and proton donor.

It is also known that [0036] disclosed antiviral composition can make the pathogenic virus inactivation or it is eliminated, and comprises rhinovirus, rotavirus, influenza virus, parainfluenza virus, Respiratory Syncytial Virus(RSV) and Norwalk virus.For example, U.S. Pat 4,767,788 disclose the use glutaric acid makes virally inactivated or it is eliminated, and comprises rhinovirus.U.S. Pat 4,975,217 disclose the composition that contains organic acid and anion surfactant, as the preparation of soap or lotion, are used for control virus.United States Patent (USP) publication 2002/0098159 discloses the use proton medicament and surfactant is provided, and comprises the antibacterium surfactant, realizes antiviral and the antibacterium performance.

[0037] U.S. Pat 6,034, and 133 disclose a kind of viricidal hand lotion, and it contains malic acid, citric acid and C _1-6Alcohol.U.S. Pat 6,294,186 disclose benzoic acid analog for example the coupling composition of salicylic acid and selected slaine can effectively resist virus, comprise rhinovirus.U.S. Pat 6,436,885 disclose the antibacterial agent known under 2 to 5.5 pH value condition and the composition of 2-Pyrrolidone-5-carboxylic acid, and antibacterium and antiviral performance are provided.

[0038] organic acid in the personal wash compositions is also disclosed.For example, WO 97/46218 and WO 96/06152 disclose and used organic acid or salt, hydrotropic solvent, triclosan and hydroxyl solvent in the surfactant base-materials of antimicrobial cleansing compositions.These publications are not put down in writing antiviral performance.

[0039] people's such as Hayden AntimicrobialAgents and Chemotherapy, 26:928-929 (1984) disclose the hand lotion that contains remaining viricidal activity by use and have blocked the hand adversary of rhinovirus flu and propagate.Make aspect some type rhinovirus inactivation, the hand lotion that contains 2% glutaric acid is more effective than placebo.Yet publication discloses the rhinovirus serotype that the lotion that contains glutaric acid can not effectively be resisted wide region.

[0040] is known for the people who infects common cold uses the fabric that kills the virus that designs, and comprises citric acid, malic acid and lauryl sodium sulfate.Yet, people such as Hayden (Journalof Infectious Diseases, 152:493-497 (1985)) report, hand adversary that can blocking virus with inactivation of virus mass treatment or untreated paper handkerchief propagates.Therefore, not having unique benefit aspect the propagation of prevention rhinovirus flu may be owing to the composition that is incorporated in the fabric that kills the virus.

[0041] be difficult to obtain effective directed toward bacteria and both effective antimicrobial compositions of virus, this is owing to have basic difference between bacterium and virus.Though there are many antimicrobial cleansing products at present, product form different (for example deodorant soap, hard surface cleaner and operation disinfectant), but this antimicrobial products has typically been introduced antimicrobial, for example phenol type compound and/or coarse surfactant, it can make the skin tissue dry and uncomfortable.Ideally, the cleaning skin that personal cleansing product can be mild, producing seldom or does not almost have excitant, and can not make skin over-drying after frequent the use.

[0042] correspondingly, existence comprises virus and Gram-positive and Gram-negative bacteria for efficient anti-broad-spectrum micro-organisms at short notice, the needs of antimicrobial compositions, wherein composition and method can provide the antimicrobial acivity of lasting and broad spectrum activity, and are gentle to skin.The antimicrobial compositions that contains alcohol of the present invention can provide to demonstrate the personal care product that improved mildness and the virus of improving the standard and bacterium reduce.

The present invention's general introduction

[0043] the present invention relates to contain the antimicrobial compositions of alcohol, it can provide quick and lasting antiviral effect in less than about one minute, and can be fast and cut down Gram-positive and Gram-negative bacteria significantly.More particularly, the present invention relates to comprise following antimicrobial compositions: (a) sterilization alcohol, (b) contain C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, cetearyl alcohol pure and mild ceteareth-20 blend for example, (c) optional organic acid and (d) water.Contain the organic acid composition and have about 5 or littler pH value.Contain the organic acid composition organic acid residual layer can be provided on the processing surface.

[0044] the invention still further relates to and contain sterilization alcohol, do not contain organic acid bactericidal composition, for example hand sanitizer.This composition can further contain active antibacterial agent, for example phenol and quaternary ammonium antibacterial agent.This composition does not contain the clean surface activating agent of intentional adding, for example anionic, cationic and amphoteric surfactant.

[0045] correspondingly, one aspect of the present invention provides antimicrobial compositions, its deactivation for broad spectrum of bacteria is fruitful, comprise Gram-positive and Gram-negative bacteria, staphylococcus aureus (S.aureus) for example, hog cholera Salmonella (S.choleraesuis), Escherichia coli (E.coli) and Friedlander (K.pneumoniae), make simultaneously to harmful virally inactivated of health or with it and eliminate, especially nonenveloped virus, for example sour unsettled virus, rhinovirus particularly, other sour unsettled picornavirus.Said composition also can effectively make influenza virus and rotavirus inactivation or with its elimination.In preferred embodiments, compare with the antimicrobial compositions of now, the anti-microbial effect of composition obtains prolonging.

[0046] another aspect of the present invention provides and has comprised following liquid anitmicrobial composition:

(a) the sterilization alcohol of about 25% to 75% weight, for example C _1-6Alcohol;

(b) C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, for example cetearyl alcohol pure and mild ceteareth-20 blend;

(c) kill the virus one or more organic acid of effective dose; With

(d) water,

Wherein composition has about 5 or littler pH value.

[0047] in preferred embodiments, said composition provides on the processing surface and has comprised organic acid continuous basically layer or film, so that give lasting antiviral activity for the surface of handling.In other preferred embodiment, said composition does not contain the surfactant of intentional adding.

[0048] another aspect of the present invention provides and has comprised the organic acid antimicrobial compositions, and it is a large amount of for skin, and/or can not infiltrate skin, and/or withstands the skin flushing, and/or it forms continuous basically barrier layer on skin.This organic acid typically has the log P less than 1, and said composition is effectively at broad spectrum of bacteria, demonstrates synergistic activity at virus.Lasting antiviral activity is partly because lip-deep organic acid residual layer or the film handled, and it can be after through flushing several times and can not remove from skin, and during routine work normally one period of maintenance several hrs.

[0049] preferred compositions comprises one or more polybasic carboxylic acid and polymeric acid.These compositions provide effective and lasting control to virus, and demonstrate the synergistic activity at Gram-positive and Gram-negative bacteria.

[0050] another aspect of the present invention provides antimicrobial compositions, it can withstand the skin flushing, for example after three water flushings, the non-volatile component of at least 50%, at least 60% and preferred at least 70% the composition of using be retained in handle on the surface, after ten water flushings, the composition of effective antiviral quantity is retained on the skin.

[0051] irrelevant with organic acid log P, this antimicrobial compositions provides quick and lasting control and the deactivation of broad spectrum of bacteria fast to nonenveloped virus.Said composition also provides the lasting control to influenza virus.In one embodiment, organic acid has the water-octanol distribution coefficient (being expressed as log P) less than 1, and composition demonstrates synergistic activity at nonenveloped virus.In another embodiment, organic acid has one or bigger log P, and the composition directed toward bacteria demonstrates synergistic activity.In another embodiment, organic acid comprises and has log P less than 1 first organic acid with to have log P be 1 or the second bigger organic acid, and composition demonstrates synergistic activity at nonenveloped virus and bacterium.

[0052] another aspect of the present invention provides and has comprised following liquid hand sanitizing composition:

(a) about 25% sterilization alcohol to about 75% weight;

(b) C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, for example cetearyl alcohol pure and mild ceteareth-20 blend; With

(c) water.

[0053] another aspect of the present invention provides antimicrobial compositions, and it demonstrates substantial, wide spectrum and persistent virus control and substantial and bacterial control wide spectrum.Said composition has the power of preserving moisture of raising, and stops the alcohol evaporation.Correspondingly, in theory, the anti-microbial effect of alcohol obtains prolonging.

[0054] another aspect of the present invention provides the antimicrobial compositions with antibacterium and antiviral activity, comprises: (a) sterilization alcohol, (b) C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, it can stop the alcohol evaporation, with the increase anti-microbial effect, (c) organic acid, it is a large amount of for skin, and/or it can not infiltrate skin, and/or its anti-skin flushing, and/or it forms continuous basically barrier layer, for example hydrophobic monocarboxylic acid, polybasic carboxylic acid, polymeric acid or its mixture with multiple carboxylic acid, phosphate, sulphonic acid ester and/or sulfuric ester part on skin, (d) water, wherein composition has about 5 or littler pH value.

[0055] organic acid typically has the log P less than 1, and composition is effectively at broad spectrum of bacteria, and composition demonstrates synergistic activity at nonenveloped virus.Said composition also can effectively be resisted influenza virus.Lasting antiviral activity is partly because lip-deep organic acid residual layer or the film of comprising of handling, and it can be through after washing and can not remove from skin several times, and keep several hrs during routine work normally.

[0056] another aspect of the present invention provides the antimicrobial compositions with antibacterium and antiviral activity, comprises: (a) sterilization alcohol, (b) C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, for example cetearyl alcohol pure and mild ceteareth-20 blend and (c) water.These compositions provide effectively controlling with prolonging of Gram-positive and Gram-negative bacteria.

[0057] another aspect of the present invention provides antimicrobial compositions, after contacting 30 seconds, it demonstrates at least 4 logarithm minimizing at nonenveloped virus with at rotavirus serotype, the for example sour unsettled virus of nonenveloped virus, comprise rhinovirus serotype, for example rhinovirus 1a, rhinovirus 2, rhinovirus 14 and rhinovirus 4, rotavirus serotype is rotavirus Wa for example.30 second time of contact after using, this antimicrobial compositions also provides about at least 5 hours about 3 logarithm to reduce at nonenveloped virus and about 6 hours at least 2 logarithm minimizing.In some embodiments, this antimicrobial compositions provides the logarithm up to about eight hours 2 to reduce at nonenveloped virus.

[0058] another aspect of the present invention provides antimicrobial compositions, contact 30 seconds after, this antimicrobial compositions demonstrates at least 2 logarithm at Gram-positive bacteria (being staphylococcus aureus) to be reduced.

[0059] another aspect of the present invention provides antimicrobial compositions, contact 30 seconds after, this bactericidal composition demonstrates at least 2.5 logarithm at Gram-negative bacteria (being Escherichia coli) to be reduced.

[0060] another aspect of the present invention provides the consumer products based on antimicrobial compositions of the present invention, for example, skin cleaner, body sprays, operation abrasive cleaner, Wound care agent, hand with sanitizer, disinfectant, shampoo for pets, inanimate surfaces sanitizer, lotion, ointment, emulsifiable paste, or the like.Composition of the present invention is the conservative product.Make composition be retained in handle on the surface, thereby the volatile component of composition is evaporated at leisure.Said composition is desirable to skin on aesthetic, and to the skin nonirritant, to the inanimate surfaces non-corrosiveness, and provides continuous basically residual film of non-volatile organic acid or layer on skin.

[0061] further aspect of the present invention provides quick control animal tissue, comprise human tissue, on wide spectrum virus and the method for Gram-positive and Gram-negative bacteria population, this method is passed through: make and for example organize that corium contacts time enough with the present composition, for example about 15 seconds to 5 minutes or longer, for example about one hour, so that bacterium and virus population level are reduced to target level.Further aspect of the present invention provides composition, and said composition can be controlled the virus in the animal tissue lastingly and prolong the bacterium of controlling in the animal tissue.

[0062] another aspect of the present invention provides treatment or pre-anti-virus institute disease mediated method with illness, and this disease and illness be caused by rhinovirus, picornavirus, adenovirus, herpes virus, Respiratory Syncytial Virus(RSV) (RSV), coronavirus, enterovirus, rotavirus and other nonenveloped virus.This method and composition also can be treated disease and the illness virus-mediated with flu-prevention.

[0063] another aspect of the present invention provides blocking virus to be transmitted to life the surface particularly composition and the method for human skin from life and inanimate surfaces.Provide the control nonenveloped virus especially, rhinovirus especially, the method and composition of propagation, by giving after the dermal administration composition, control is present in the virus on the human skin effectively, and about four or more hours of continuous control virus, up to about 8 hours, time.

[0064] these and other new aspect and benefit of the present invention have been listed in the non-limiting detailed description of preferred embodiment below.

Brief description of drawings

[0065] Fig. 1 a and 1b are the reflection micrographs, have shown the lip-deep organic acid barrier layer that is provided after the surface applied present composition is provided;

[0066] Fig. 1 c and 1d are the reflection micrographs, have shown not have barrier layer on the surface afterwards for the surface applied reference composition; With

[0067] Fig. 2 and 3 is to the % moisture capacity of dermal administration invention and the reference composition curve to time of contact.

Detailed description of preferred embodiments

[0068] personal care product of introducing active antimicrobial agent is known many year.Because antimicrobial personal care product's introducing provides antimicrobial properties to make many claims to this product.The most effectively, antimicrobial compositions should provide high logarithm to reduce at the broad-spectrum biological body in short as far as possible time of contact.In theory, composition also should make virally inactivated.

[0069] preparation at present, the most commercial liquid antibacterium soap composition provides the inactivating efficacy to the edge of difference, the i.e. speed of killing bacteria.These compositions can not be controlled virus effectively.

[0070] antimicrobial hand does not typically contain surfactant with sanitizing compositions, and relies on the alcohol of high concentration to control bacterium.The alcohol evaporation, and therefore can not provide lasting bacterial control.Alcohol also may make dry skin and discomfort.The present invention relates to contain the composition of alcohol, it can keep moistening, and stops the alcohol evaporation, can prolong anti-bacterial effect again and reduce skin irritation.

[0071] most of existing product especially lacks the effect at Gram-negative bacteria, Escherichia coli for example, and it is particularly related to health.Yet, there is the composition of extra high wide spectrum anti-bacterial effect really, to measure by the quick inactivating (being time limit deactivation (time kill)) of bacterium, it is different from lasting deactivation.These products also lack enough antiviral activities.

[0072] with previous introducing alcohol at high proportion, promptly 40% or bigger weight, composition compare, this antimicrobial compositions provides outstanding broad-spectrum antiviral and anti-bacterial effect, and has improved antiviral effect significantly.The basis of this improvement effect is: (a) find the pure and mild organic acid of sterilization, particularly have organic acid less than about 1 log P, coupling can improve antiviral effect in fact and (b) give surface pH value after the surface applied composition.Lack the organic acid composition and also shown the anti-bacterial effect that prolongs.

[0073] one aspect of the present invention is the skin pH value that keeps low for a long time, so that lasting antiviral activity to be provided.In preferred embodiments, this is to obtain by the continuous basically film that forms non-volatile composition component on skin, and it can provide the organic acid bank, to keep low skin pH value.

[0074] term " continuous basically film " is meant the residue of non-volatile component of the composition of barrier layer form, is present in handled surface area regions at least 50%, at least 60%, at least 70% or at least 80% preferably at least 85% or at least 90% and more preferably at least 95%.In the reflection micrograph of figure, shown " continuous basically " film, hereinafter will discuss it.Term used herein " continuous basically film " and term " continuous basically layer ", " barrier layer " and " barrier film " synonym.

[0075] the pure and mild organic acid co-action that has less than one log P of sterilization, thereby control nonenveloped virus.Sterilizing pure and mildly has one or the organic acid co-action of bigger log P, thereby improves anti-bacterial effect in fact.Have less than first organic acid of one log P and have one or the coupling of second organic acid of bigger log P and sterilization alcohol, aspect control nonenveloped virus and Gram-positive and Gram-negative bacteria, can provide the synergy of raising.

[0076] though contain antimicrobial for example the composition of triclosan shown quick and effective antibacterial activity at Gram-positive and Gram-negative bacteria, virus control insufficient.Aspect the propagation of control numerous disease, the virus control on skin and the inanimate surfaces is very important.

[0077] for example, rhinovirus is the most important microorganism relevant with the acute respiratory disease that is called " common cold ".Know that also other virus for example parainfluenza virus, Respiratory Syncytial Virus(RSV) (RSV), enterovirus and coronavirus can cause the symptom of " common cold ", but rhinovirus can cause the common cold of maximum number in theory.The rhinovirus virus that causes flu still the most rambunctious, and have the ability that survives more than four days on the stiff surface.In addition, in case contact 70% ethanolic solution, most of virally inactivated.Yet rhinovirus contact ethanol but still can be survived.

[0078] because rhinovirus is the main known reason of common cold, so importantly, the composition with antiviral activity is active at rhinovirus.Though understood rhinoviral molecular biology now, successfully found the prevention caused flu of rhinovirus and prevent virus disseminating to give the not effective ways of infected patient.

[0079] known iodine is a kind of potent antiviral agent, and lasting rhinovirus activity can be provided on skin.In tentative flu of inducing with during the propagation of flu is studied naturally, use the patient of iodine product still less to catch a cold than placebo user significantly.This shows that iodine can effectively prolong the cycle that the blocking-up rhinovirus infection is propagated.Thus, exploitation can provide fast and the product of permanent disease-resistant cytotoxic activity is being effective reducing aspect the incidence of catching a cold.Equally, the composition that local application demonstrates antiviral activity can effectively prevent and/or treat by other nonenveloped virus, comprises sour unsettled virus and the caused disease of influenza virus.

[0080] rotavirus also is environmentally stable virus.Rotavirus infection is gastral infection, and is cacatory common cause among the children, causes the hospitalization of 50,000 examples every year separately in the U.S..Rotavirus infection especially is a problem in airtight community, for example childcare mechanism, the elderly's medical facility, family, children's hospital.

[0081] the general mode of propagating rotavirus is that the person to person propagates by the hand that pollutes, and also may take place by eating polluted water or food but propagate, or takes place by contacting with contaminated surface.Rotavirus enters health by contacting with the oral cavity then.

[0082] knownly washes one's hands and wash stiff dough and can not kill rotavirus, but can help to prevent its propagation with soap and/or other cleaning agent.In the U.S., to ratify oral Rotavirus Vaccine and be used for children, but do not advised using it, this is because serious adverse side effect.Because existing other effective ways of not eliminating rotavirus or its propagation, in airtight community, especially the staff who caters in those communities of children must adhere to strict health practice, with the propagation that helps to subdue rotavirus.Make aspect the rotavirus inactivation, have the antiviral effect of increase, comprising lasting antiviral effect, the improvement composition will further subdue the propagation of rotavirus infection.

[0083] expression of killing the virus can make virally inactivated or it is eliminated.Term used herein " lasting antiviral effect " or " lasting antiviral activity " are meant: after using, retain residues or give certain condition on life surface (for example skin) or inanimate surfaces, thus the significant antiviral activity of time expand is provided.In some embodiments, " lasting antiviral effect " or " lasting antiviral activity " is meant: after using, on life (for example skin) or inanimate surfaces, keep antiviral agent, comprise organic acid, barrier residue or film, thereby the significant antiviral activity of time expand is provided.Barrier residue or film can be continuously or continuous basically, and can resist between the water flush period from the removal on handle surface.

[0084] contacting with composition within 30 seconds, the present composition comprises sour unsettled virus at nonenveloped virus, for example rhinovirus and rotavirus serotype, lasting antiviral effect is provided, and promptly preferred at least 3 logarithm reduces, and the more preferably logarithm of log4 minimizing at least.After composition contacted, antiviral activity can keep about at least 0.5 hour, and preferably about at least one hour, and more preferably about at least two hours, about at least three hours, or about at least four hours.In some preferred embodiments, after composition contacted, antiviral activity can keep about six to about eight hours.In some embodiments, lasting antiviral activity is owing to be present in the barrier layer or the storage of the organic acid in the film of the lip-deep composition of handling at least in part.The employed method of permanent disease-resistant toxic effect fruit of measuring will be discussed below.

[0085] antimicrobial compositions of the present invention is providing fast and wide spectrum control bacterium and to control fast and lastingly aspect the nonenveloped virus be fruitful.In one embodiment, efficient composition comprises sterilization alcohol, C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol, for example organic acid of cetearyl alcohol pure and mild ceteareth-20 blend and the effective dose of killing the virus.In another embodiment, composition comprises the pure and mild C of containing of sterilization ₁₂To C ₂₂The C of alcohol and ethoxylation ₁₂To C ₂₂The blend of alcohol.

[0086] the pure and mild organic acid co-action that has less than about 1 log P of sterilization, thereby control wide spectrum nonenveloped virus.Sterilizing pure and mildly has 1 or the organic acid co-action of bigger log P, thus the control broad spectrum of bacteria.Contain and have less than first organic acid of 1 log P and have 1 or the second organic acid composition of bigger log P, can co-action, thus control wide spectrum nonenveloped virus and wide spectrum Gram-positive and Gram-negative bacteria.

[0087] said composition has the power of preserving moisture of raising, and postpones the alcohol evaporation.Said composition is gentle surprisingly for skin, and for the inanimate surfaces non-corrosiveness.Thus, provide the compositions useful that solves prolongation bacterial control and lasting viral control problem to the consumer.

[0088] this composition provides the effective and lasting inactivation of nonenveloped virus.Nonenveloped virus is including, but not limited to adenovirus, papovavirus, PCV-II, parvovirus, birnavirus, astrovirus, calicivirus (comprising Norwalk virus), rotavirus, and picornavirus (comprising rhinovirus, bone marrow poliomyelitis virus, and hepatitis A virus).Said composition also can make the influenza virus inactivation.

[0089] antimicrobial compositions of the present invention can highly effectively be used for household cleaning (stiff dough for example, for example floor, table top, bathtub, dish, with the soft cloth material, clothes for example), personal nursing (for example, lotion, shower gels agent, soap, shampoo and cleaning piece) and industry and hospital's (for example sterilization of instrument, medical equipment and gloves).This composition can be effectively and is sterilized apace and infected or surfaces contaminated by Gram-negative bacteria, Gram-positive bacteria and nonenveloped virus (for example rhinovirus).This composition also provides the lasting antiviral effect and the anti-bacterial effect of prolongation.

[0090] this composition can the external and interior use of body.External being meant in no life thing or on it is needed fixing or use, have on the lifeless object of hard or pressure release surface at the prevention virus disseminating particularly, the most especially on the object of staff contact.Be meant in the body in the life object or on it, particularly on mammal skin, especially on hand.

[0091] illustrated as following non-limiting embodiments, antimicrobial compositions of the present invention comprises: (a) the about 25% sterilization alcohol to about 75% weight; (b) about 0.1% the C that contains to about 20% weight ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂The blend of alcohol; (c) organic acid of the optional effective dose of killing the virus; (d) water.In another embodiment, composition does not contain organic acid, and effective bacterial control can be provided on the processing surface.Contain the organic acid composition and have pH value, and typically can on the processing surface, form the continuous substantially film or the layer of organic acid and other non-volatile composition component less than about 5.Especially, after ten flushings, the composition component of effective dose is retained in institute and handles on the surface, and after washing for three times, at least 50%, preferably at least 60% and more preferably at least 70% non-volatile composition component is retained on the handled surface.In preferred embodiments, composition further contains optional gelling agent.In other embodiments, composition contains active antibacterial agent.

[0092] in handling the embodiment of skin, " flushing " be meant have about 30 ℃ gently rub to the condition of the running water that slowly flows of about 40 ℃ temperature the skin of handling about 30 seconds, air-dry then skin.

[0093] contact after 30 seconds, composition demonstrates about 2 logarithm minimizing at Gram-positive bacteria.Contact after 30 seconds, composition also demonstrates about 2.5 logarithm minimizing at Gram-negative bacteria.Contact after 30 seconds, contain the organic acid composition at nonenveloped virus, comprise sour unsettled virus, rhinovirus serotype for example, further demonstrate about 5 logarithm minimizing, contacted about 5 hours afterwards, demonstrated at least 3 logarithm minimizing at these sour unsettled viruses, with contact after about 6 to about 8 hours, demonstrate about at least 2 logarithm and reduce.Antiviral composition still is soft, needn't be from skin flushing or wiping composition.

[0094] according to the present invention, this antimicrobial compositions can further comprise hereinafter disclosed other optional components, for example active antibacterial agent, hydrotropic solvent, many hydroxyls solvent, gelling agent, pH value conditioning agent, vitamin, dyestuff, skin conditioning agent and spices.Composition does not contain the clean surface activating agent of intentional adding, for example anion surfactant.

[0095] following component is present in the bactericidal composition of the present invention.

A. sterilization is pure

[0096] antimicrobial compositions of the present invention contains the about 25% sterilization alcohol to about 75% weight.The preferred embodiments of the invention contain the about 30% sterilization alcohol to about 75% weight.Most preferred embodiment of the present invention contains the about 30% sterilization alcohol to about 70% weight.

[0097] term used herein " sterilization alcohol " is meant the water-soluble alcohol that contains 1 to 6 carbon atom, i.e. C _1-6Alcohol.Sterilization alcohol is including, but not limited to methyl alcohol, ethanol, propyl alcohol and isopropyl alcohol.B.C ₁₂To C ₂₂The C of pure and mild ethoxylation ₁₂To C ₂₂The blend of alcohol

[0098] this composition contains C ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂The blend of alcohol, quantity approximately be composition 0.1% to about 20% weight, preferably approximately 1% to about 15% weight.In order to obtain whole benefit of the present invention, composition contains about 1.5% mixture to about 12% weight.Mixture contains about 10% to about 90% C ₁₂To C ₂₂Alcohol and about 10% to about 90% ethoxylation C ₁₂To C ₂₂Alcohol.Ethoxylation C ₁₂To C ₂₂Alcohol contains about 6 to about 36 ethoxy units.

[0099] be applied to after the surface, mixture can help to keep the wettability of composition, therefore, can stop sterilization alcohol from surface evaporation.This effect has prolonged the anti-microbial effect of composition, and after reusing composition, can reduce skin irritation.

[00100] C that uses in the blend ₁₂To C ₂₂The non-limitative example of alcohol comprises docosyl alcohol, C _12-13Alcohol, C _12-15Alcohol, C _12-16Alcohol, C _14-15Alcohol, cetostearyl alcohol, cetanol, lauric alcohol, different cetanol, isooctadecane alcohol, laruyl alcohol, tetradecanol, oleyl alcohol, palm kernel alcohol, octadecanol, tallow alcohol, tridecanol and its mixture.

[00101] ethoxylation C ₁₂To C ₂₂The non-limitative example of alcohol comprises: docosyl alcohol polyethers-10, docosyl alcohol polyethers-20, docosyl alcohol polyethers-30, C _11-15Alkanol polyethers-12 (C _11-15Pareth-12), C _11-15Alkanol polyethers-20, C _11-15Alkanol polyethers-30, C _11-15Alkanol polyethers-40, C _11-21Alkanol polyethers-10, C _12-15Alkanol polyethers-12, C _14-15Alkanol polyethers-11, C _14-15Alkanol polyethers-13, C _22-24Alkanol polyethers-33, ceteareth-10, ceteareth-11, ceteareth-12, ceteareth-15, ceteareth-17, ceteareth-20, ceteareth-25, ceteareth-27, ceteareth-30, cetanol polyethers-10, cetanol polyethers-12, cetanol polyethers-15, cetanol polyethers-16, cetanol polyethers-20, cetanol polyethers-24, cetanol polyethers-25, cetanol polyethers-30, celoleth-25, cholesterol polyethers-10, cholesterol polyethers-24, decyl tetradecyl alchohol polyethers-30, dihydrocholesterol polyethers-15, dihydrocholesterol polyethers-30, dodecyl phenol polyethers-12, glycerin polyether-12, glycerin polyether-26, different cetanol polyethers-10, different cetanol polyethers-20, different cetanol polyethers-30, different laureth-10, isooctadecanol polyethers-10, isooctadecanol polyethers-12, isooctadecanol polyethers-20, isooctadecanol polyethers-22, lanolin alcohol polyethers-10, lanolin alcohol polyethers-15, lanolin alcohol polyethers-16, lanolin alcohol polyethers-20, lanolin alcohol polyethers-25, laureth-10, laureth-11, laureth-12, laureth-13, laureth-14, laureth-15, laureth-20, laureth-23, laureth-25, laureth-30, oleth-10, oleth-12, oleth-15, oleth-16, oleth-20, oleth-23, oleth-25, sorbierite polyethers-20, stearyl alcohol polyethers-10, stearyl alcohol polyethers-11, stearyl alcohol polyethers-13, stearyl alcohol polyethers-15, stearyl alcohol polyethers-16, stearyl alcohol polyethers-20, stearyl alcohol polyethers-21, stearyl alcohol polyethers-25, stearyl alcohol polyethers-27, stearyl alcohol polyethers-30, tridecanol polyethers-10, tridecanol polyethers-11, tridecanol polyethers-12, tridecanol polyethers-15 and its mixture.

[00102] can be with C ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂Alcohol joins in the composition respectively, or carries out premixed, joins in the composition then.In addition, useful blend can obtain with following form commercial: Cosmowax, Cosmowax B, Cosmowax BP, Cosmowax D, Cosmowax EM5483, Crodex N and Cosmowax J Pastilles are obtained from Croda Chemicals Europe Ltd., East Yorkshire, England.These blends are cetearyl alcohol pure and mild ceteareth-20 blend typically.CosmowaxJPastilles is the blend of cetostearyl alcohol, stearyl alcohol polyethers-20 and stearate-10.Cetearyl alcohol pure and mild ceteareth-20 blend also can be obtained from the Emulgrade1000NI of Cognis.

C. Ren Xuan organic acid

[00103] in one embodiment, this antimicrobial compositions also contains organic acid, and its quantity is enough to control virus and the bacterium on the antimicrobial compositions institute contact surface and make its inactivation.Organic acid works synergistically with sterilization alcohol, thereby controls virus and/or bacterium fast, and lasting virus control is provided.

[00104] especially, organic acid is present in the composition, and its quantity is enough to make the life that composition contacts or the pH value of inanimate surfaces to be reduced to the degree that can obtain lasting virus control.No matter whether rinse out composition or be retained on the contact-making surface, all can obtain this lasting virus control from contact-making surface.Organic acid keeps disassociation at least in part in composition, and can so keep when diluted composition or during using the time.

[00105] in case be applied to the surface, human skin for example, surface pH value reduces fully, to obtain lasting virus control.In preferred embodiments, the organic acid surplus remains on the skin, even after rinsing step, is preferably formed film or layer, so that give lasting virus control.Yet even organic acid is fully fallen from surface washing basically, surface p H value reduces fully, can control virus at least 0.5 hour.

[00106] this composition is conservative (leave-on) composition, promptly can not rinse out from skin.Yet after three flushings, at least 50% non-volatile composition component keeps from the teeth outwards, and after ten flushings, the composition of effective dose is retained on the handled surface.

[00107] typically, organic acid (if really exist) is included in this composition, its quantity be composition about 0.1% to about 15% weight, preferably approximately 0.3% to about 10% weight.In order to obtain whole benefit of the present invention, the amount that organic acid exists be composition about 0.5% to about 8% weight.In preferred embodiments, the organic acid mixture is included in the composition.Organic acid total amount in the composition is relevant with employed organic acid classification, and with specific acid or use acid characteristic relevant.

[00108] preferred, be included in organic acid in this antimicrobial compositions and can not penetrate in the surface that it uses, for example, skin is opposite with infiltrating, it is retained on the skin surface, on skin with any non-volatile composition component cambium or film.Therefore, preferred organic acid is hydrophobic organic acid.

[00109] in one embodiment of the invention, organic acid has the log P less than 1, preferably less than 0.75.In order to obtain whole benefit of the present invention, organic acid has the logP less than 0.5.In this embodiment, the pure and mild organic acid of sterilizing works synergistically, so that effective and lasting virus control to be provided.

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

[00111] predictably, by will have less than first organic acid of 1 log P and have 1 or second organic acid of bigger log P be incorporated in this composition, first and second organic acids can work synergistically with sterilization alcohol, thereby the lasting control of nonenveloped virus and the control of broad spectrum activity bacterium are provided.Can also make influenza virus and rotavirus inactivation.

[00112] term used herein " log P " is defined as: when balance and 25 ℃, the log of water-octanol distribution coefficient, that is, and ratio P _w/ P _oLog, P wherein _wBe the concentration of organic acid in water, P _oBe the concentration of organic acid in octanol.Water-octanol coefficient can utilize following mensuration: U.S.Environmental Protection Agency Procedure, ＂ OPPTS 830.7560Partition Coefficient (n-Octanol/Water), Generator Column Method ＂ (1996).

[00113] has less than the organic acid of 1 log P water-fastly typically, for example have water-soluble less than about 0.5wt% at 25 ℃.Think have 1 or the organic acid of bigger log P water-soluble typically, for example have the water-soluble of 0.5wt% at least at 25 ℃.

[00114] organic acid can comprise monocarboxylic acid, polybasic carboxylic acid, have a plurality of carboxylic acids, polymeric acid or its mixture of phosphate, sulphonic acid ester and/or sulfuric ester part.Except acid moieties, organic acid can also contain other parts, for example hydroxyl and/or amino.In addition, can in the present composition, use organic acid anhydride as organic acid.Preferred organic acid is polybasic carboxylic acid, polymerization of carboxylic acid or its mixture.

[00115] in one embodiment, organic acid comprises and has structure RCO ₂The monocarboxylic acid of H, wherein R is C _1-6Alkyl, hydroxyl C _1-6Alkyl, halo C ₁-C ₆The phenyl of alkyl, phenyl or replacement.Alkyl can be replaced by phenyl and/or phenoxy group, and phenyl and phenoxy group can be replacements or unsubstituted.

[00116] non-limitative example of the monocarboxylic acid that uses in the present invention is an acetate, propionic acid, glycolic acid, lactic acid, benzoic acid, phenylacetic acid, phenoxyacetic acid, zimanic acid, 2-, 3-or 4-hydroxybenzoic acid, aminobenzenesulfonic acid (anilic acid), adjacent, or rubigan acetate, adjacent, or parachlorophen-oxyacetic acid and its mixture.The benzoic acid of other replacement is disclosed in U.S. Pat 6,294, and in 186, this paper is introduced into as a reference.The benzoic example that replaces is including, but not limited to salicylic acid, 2-nitrobenzoic acid, thiosalicylic acid, 2, the 6-dihydroxy-benzoic acid, 5-nitro-salicylic acid, 5 bromosalicylic acid, 5-iodo-salicylic acid, 5-fluoro salicylic acid, 3-chloro-salicylic acid, 4-chloro-salicylic acid and 5-chloro-salicylic acid.

[00117] in another embodiment, organic acid comprises polybasic carboxylic acid.Polybasic carboxylic acid contains at least two and four carboxylic acid groups of as many as.Except replacement and unsubstituted phenyl, polybasic carboxylic acid can also contain hydroxyl or amino.

[00118] non-limitative example of the polybasic carboxylic acid that uses in the present invention comprises malonic acid, succinic acid, glutaric acid, adipic acid, terephthalic acid (TPA), phthalic acid, pimelic acid, suberic acid, azelaic acid, decanedioic acid, fumaric acid, maleic acid, tartaric acid, malic acid, citric acid, maleic acid, aconitic acid and its mixture.

[00119] acid anhydrides of polycarboxylic acid and monocarboxylic acid also is the organic acid that uses in this composition.Preferred acid anhydrides is the acid anhydrides of polybasic carboxylic acid, for example phthalic anhydride.Because the pH value of composition, at least a portion acid anhydrides is hydrolyzed to carboxylic acid.Predictably, acid anhydrides can hydrolysis at leisure on the surface of composition contact, helps to provide lasting antiviral activity thus.

[00120] in the 3rd embodiment, organic acid comprises polymerization of carboxylic acid, polymerization sulfonic acid, sulfated polymers, polymer phosphate or its mixture.Polymeric acid has about 500g/mol to 10, and 000, the molecular weight of 000g/mol, and comprise homopolymers, copolymer and its mixture.Preferably, polymeric acid can form substantial film from the teeth outwards, and has the glass transition temperature T less than 25 ℃ _g,, and be more preferably less than about 15 ℃ preferably less than 20 ℃.Glass transition temperature be amorphous material for example polymer be changed to the temperature of mecystasis by the vitreousness of fragility.Those skilled in the art use standard technique can easily measure the T of polymer _g

[00121] polymeric acid is uncrosslinked or is crosslinked with only hanging down very much limit.Polymeric acid typically by have at least one hydrophilic segment for example the vinylation unsaturated monomer of carboxyl, carboxylic acid anhydrides, sulfonic acid and sulfuric ester prepare.Polymeric acid can contain comonomer, and for example styrene or alkene are to improve the hydrophobicity of polymeric acid.

[00122] be used to prepare polyorganic acid monomer example including, but not limited to:

(a) contain the monomer of carboxyl, for example the unsaturated list or the polybasic carboxylic acid of single vinylation, for example acrylic acid, methacrylic acid, maleic acid, fumaric acid, crotonic acid, sorbic acid, itaconic acid, ethylacrylic acid, α-Lv Bingxisuan, alpha-cyanoacrylate, Beta-methyl acrylic acid (crotonic acid), atropic acid, β-acryloyl group oxygen base propionic acid, sorbic acid, α-chlorine sorbic acid, angelic acid, cinnamic acid, to chloro-cinnamic acid, β-stearoyl acrylic acid, citraconic acid, mesaconic acid, glutaconate, aconitic acid, three carboxyl ethene, and cinnamic acid;

(b) contain carboxylic acid anhydride group's monomer, for example the unsaturated polybasic acid anhydride of single vinylation, for example maleic anhydride; With

(c) contain sulfonic monomer; for example; aliphatic or aromatic vinyl sulfonic acid, vinyl sulfonic acid for example, allyl sulphonic acid; vinyl toluene sulfonic acid; styrene sulfonic acid, sulfoethyl (methyl) acrylate, 2-acrylamido-2-methyl propane sulfonic acid; sulfopropyl (methyl) acrylate and 2-hydroxyl-3-(methyl) acryloyl group oxygen base propyl sulfonic acid.

[00123] but polymeric acid can contain the unit of other copolymerization, other single vinylation unsaturated comonomer promptly well known in the art is as long as polymer is that (promptly at least 10%, preferably at least 25%) comprises the monomeric unit of acidic group in fact.In order to obtain whole benefit of the present invention, polymeric acid comprises at least 50% and more preferably at least 75% and the monomeric unit that comprises acidic group of as many as 100%.Other combined polymerization unit for example can be styrene, alkene, alkyl acrylate or alkyl methacrylate.Also polymeric acid partly can be neutralized, this can promote that polymeric acid is distributed in the composition.Yet needs keep the unneutralized acidic group of sufficient amount, with reduction skin pH value, and give lasting antiviral activity.

[00124] polymeric acid can help to form residual organic acid film or layer on skin, and further promotes to form on skin the more continuous layer of residual organic acid.Polymeric acid typically is used in combination with monocarboxylic acid and/or polybasic carboxylic acid.

[00125] a kind of preferred polymeric acid is a polyacrylic acid, both can be that homopolymers also can be copolymer, for example 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 exemplary polymeric acid of using in the present invention including, but not limited to:

Carbomer	(CARBOPOL 910，934，934P， 940，941，ETD 2050；ULTREZ 10，21) (CARBOPOL ETD 2050)
		Acrylate/C20-30 alkyl acrylate cross-linked copolymer	(ULTREZ 20)
Acrylate/docosyl alcohol polyethers (beheneth) 25 methacrylate copolymers	(ACULYN 28)
		Acrylate/stearyl alcohol polyethers (steareth) 20 methacrylate copolymers	(ACULYN 22)
Acrylate/stearyl alcohol polyethers 20 methacrylate cross-linked copolymers	(ACULYN 88)
		Acrylate copolymer	(CAPIGEL 98)
Acrylate copolymer	(AVALURE AC)
		Acrylate/Palmitoleyl alcohol polyethers (palmeth) 25 acrylate copolymers	(SYNTHALEN 2000)
The ammonium acrylate copolymer
		PAA/ethenol copolymer
Sodium polymethacrylate
		Acrylamide propyl three ammonium chloride/acrylate copolymers
Acrylate/acrylamide copolymer
		Acrylate/ammonio methacrylate copolymer

Acrylate/C10-30 alkyl acrylate cross-linked copolymer
		Acrylate/biacetone acrylamide copolymer
Acrylate/octyl acrylamide copolymer
		Acrylate/VA copolymer
Acrylic acid/Acrylonitrogens copolymer

[00127] in a preferred embodiment of the invention, organic acid comprises one or more polybasic carboxylic acid, for example citric acid, malic acid, tartaric acid or any two or all three these sour mixtures, with the polymeric acid that comprises a plurality of carboxyls, for example homopolymers of acrylic or methacrylic acid and copolymer.

D. carrier

[00128] carrier of this antimicrobial compositions comprises water.

E. Ren Xuan component

[00129] antimicrobial compositions of the present invention can also contain optional components well known to those skilled in the art.Concrete optional component and the quantity that may reside in the composition hereinafter are discussed.

[00130] quantity that exists of optional components should be enough to finish their expectation function, and can influence the anti-microbial effect of composition sharply, especially can influence the sterilization synergistic effect that pure and mild organic acid provided sharply.Optional components typically exist respectively or jointly composition 0% to about 50% weight.

[00131] Ren Xuan component is including, but not limited to hydrotropic solvent, many hydroxyls solvent, antibacterial agent, gelling agent, active antibacterial agent, dyestuff, spices, pH value conditioning agent, thickener, viscosity modifier, chelating agent, skin conditioning agent, softening agent, preservative, buffer, antioxidant, chelating agent, opacifier is with the optional components well known by persons skilled in the art of similar classification.

[00132] if there is hydrotropic solvent, its exist quantity be composition about 0.1% to about 30% weight, preferably approximately 1% to about 20% weight.In order to obtain whole benefit of the present invention, composition can contain about 2% hydrotropic solvent to about 15% weight.

[00133] hydrotropic solvent is to have the compound that strengthens other compound water-soluble sexuality.The hydrotropic solvent that uses in the present invention lacks surfactant properties, and short-chain alkylarenesulfonate typically.The object lesson of hydrotropic solvent is including, but 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 solvent comprises poly-sodium naphthalene sulfonate, kayexalate, methyl naphthalene sulfonic acid sodium, sodium camphorsulfonate and disodium succinate.

[00134] if there is many hydroxyls solvent, its exist quantity be composition about 0.1% to about 30% weight, preferably approximately 5% to about 30% weight.In order to obtain whole benefit of the present invention, the amount that many hydroxyls solvent exists be composition about 10% to about 30% weight.Opposite with sterilization alcohol, many hydroxyls solvent is very low for the contribution of the anti-microbial effect of this composition, if any.

[00135] term used herein " many hydroxyls solvent " is meant and contains 2 to 6 and the water miscible organic compound of two or three hydroxyls typically.Term " water miscible " is meant at 25 ℃, many hydroxyls solvent to have the water-soluble of per 100 gram water at least 0.1 many hydroxyls of gram solvent.Many hydroxyls solvent water-soluble do not have the upper limit, and for example, many hydroxyls solvent and water can dissolve in all proportions.

[00136] therefore, many hydroxyls of term solvent comprises water miscible dihydroxylic alcohols, trihydroxylic alcohol and polyalcohol.The object lesson of hydroxyl solvent is including, but not limited to ethylene glycol, propane diols, and glycerine, diethylene glycol, (two) propane diols that contracts, tripropylene glycol, hexylene glycol, butanediol, 1,2, the 6-hexanetriol, sorbitol, PEG-4 is with similar polyol.

[00137] can have gelling agent in this antimicrobial compositions, if any, its quantity is approximately the 0.01% optional gelling agent to about 5% weight, and preferred 0.1% to about 3% weight.In order to obtain whole benefit of the present invention, antimicrobial compositions can contain about 0.25% gelling agent to about 2.5% weight.Bactericidal composition typically contains the gelling agent of sufficient amount, so that composition is to be easy to apply to skin or other surperficial viscous liquid, gel or semisolid of going up and rubbing in the above.Optional gelling agent can promote composition evenly to be administered to institute to handle on the surface, and help on the processing surface, provide more continuous non-volatile composition component layer or film.Those skilled in the art's understanding is included in the type and the quantity of the gelling agent in the composition, thereby objective composition viscosity or stickiness are provided.

[00138] term " gelling agent " that here and hereinafter uses is meant the compound that can improve aqueous composition viscosity, maybe aqueous composition can be converted into gel or semisolid compound.Therefore, gelling agent can be organic matter in nature, for example, and natural gum or synthetic polymer, or can be inorganic matter in nature.

[00139] as mentioned above, this composition does not contain the clean surface activating agent.Surfactant and antimicrobial are not deliberately joined in this antimicrobial compositions, but can have 0% amount, because surfactant may reside in the commercial form of gelling agent, to help in water, to disperse gelling agent to about 0.5% weight.Surfactant also can be present in the form of additive or accessory substance in other composition component.

[00140] following is the non-limitative example of the gelling agent that can use in the present invention.Especially, following compounds, organic and inorganic both, mainly by make composition contain the water section thickening or gelling is worked:

Gum Arabic, agar, algin, alginic acid, ammonium alginate, ammonium chloride, ammonium sulfate, amylopectin, attapulgite, bentonite, calcium acetate, calcium alginate, calcium carrageenan, calcium chloride, octanol, carboxymethyl hydroxyethyl cellulose, carboxy-methyl hydroxy propyl guar gum, carrageenan, cellulose, cellulose gum, corn starch, hard gum, dextrin, dibenzylidene sorbitol (dibenzylidinesorbitol), ethene dihydro tallow acid amides, ethene two oleamide, the ethene bis-stearamides, gelatin, fruit pectin, guar gum, melon ear hydroxypropyl three ammonium chlorides, hectorite, hyaluronic acid, hydrated silica, HBMC, hydroxyethylcellulose, hydroxyethyl ethylcellulose, ethoxy stearmide-MIPA, hydroxypropyl cellulose, hydroxypropyl guar gum, hydroxypropyl methylcellulose, carragheen, kelp ashes (kelp), laruyl alcohol, locust bean gum, aluminium-magnesium silicate, magnesium silicate, magnesium trisilicate, methoxyl group PEG-22/ dodecyl glycol copolymer, methylcellulose, microcrystalline cellulose, imvite, oat meal, pectin, PEG-2M, PEG-5M, polyvinyl alcohol, potassium alginate, the sylvite of carrageenan, potassium chloride, potassium sulphate, potato starch, propylene glycol alginate, Sensor Chip CM 5 sodium, the sodium salt of carrageenan, cellulose sodium sulfate, sodium chloride, sodium silicoaluminate, sodium sulphate, oronain bentonite (stearalkonium bentonite) draws in department, oronain hectorite (stearalkonium hectorite) draws in department, the TEA-hydrochloride, bassora gum, tromethamine aluminium-magnesium silicate, wheat flour, wheaten starch, xanthans, polyvinylpyrrolidone and their derivative, vinethene derivative (methyl vinyl ether, ethyl vinyl ether, butyl vinyl ether, IVE, polymethyl vinyl ether/maleic acid), based on the polymer and the methacrylate copolymer of quaternised vinyl pyrrolidone/quaternised dimethyl aminoethyl pyrrolidones, caprolactam/vinyl pyrrolidone dimethyl amino ethyl methacrylate polymer, vinyl pyrrolidone/dimethyl amino ethyl methacrylate copolymer, stable and the naturally occurring derivative of the acid of guar gum and modification guar gum, xanthans, carboxy-propyl cellulose and its mixture modifying or replace.

[00141] other non-limitative example of following gelling agent mainly works by the non-water section thickening that makes composition:

Abienol, acrylic linoleic acid (acrylinoleic acid), mountain Yu acid aluminium, aluminium octoate, dimerized linoleic acid aluminium, double stearic acid aluminium, isostearic acid/lauric acid/palmitic acid or aluminum stearate, isostearic acid/aluminium myristate, isostearic acid/aluminum palmitate, isostearic acid/aluminum stearate, lanolin fatty acid aluminium, myristic acid/aluminum palmitate, aluminum stearate, aluminum stearate, three aluminum foil stearates, beeswax, mountain Yu acid acid amides, butadiene/acrylonitrile copolymer, C _29-70Acid, mountain Yu acid calcium, calcium stearate, candelila wax, Brazil wax, ceresine, cholesterol, cholesteryl hydroxy stearic acid ester, lauric alcohol, copal, diglycerol base stearate malate, dihydroabietyl alcohol (dihydroabietylalcohol), dimethyl lauramide oleate, dodecanedioic acid/cetostearyl alcohol/glycol copolymer, the mustard acid amides, ethyl cellulose, glyceryl triacetyl hydroxy stearic acid ester, glyceryl triacetyl ricinate, the ethylene glycol bisthioglycolate behenate, glycol dicaprylate, glycol distearate, the two stearates of hexylene glycol, hydrogenation C _6-14Olefin polymer; rilanit special; hydrogenated cottonseed oil; hydrogenated lard; the hydrogenation pilchardine; hydrogenation palm kernel glyceride; the hydrogenation palm kernel oil; HPO; Parleam; oil with hydrogenated soybean; the hydrogenated oil and fat acid amides; hydrogenated tallow glyceride; hydrogenated vegetable glyceride; hydrogenated vegetable glyceride; hydrogenated vegetable oil, hydroxypropyl cellulose, isobutene/isoprene copolymer; isocetyl stearyl stearate; Japan tallow, Jojoba haze tallow, lanolin alcohol; lauramide; the methyl dehydroabietate, hydrogenated methyl rosinate, methyl rosinate; methyl styrene/vinyl toluene copolymer; microwax, montanic acid paraffin, montan wax; the myristyl eicosanol; the myristyl octadecanol, vaccenic acid/copolymer-maleic anhydride, octyl group dodecyl stearyl stearate; oleamide; oleostearin (oleostearine), ouricury wax, oxidic polyethylene; ceresine; palm kernel alcohol, paraffin hydrocarbon, pentaerythrite hydrogenated rosins acid esters; the pentaerythrite rosinate; pentaerythrite four abietates, pentaerythrite four behenates, pentaerythrite four caprylates; pentaerythrite four oleates; pentaerythritol tetrastearate, phthalic anhydride/glycerine/glycidyl decylate copolymer, phthalic acid/trimellitic acid/glycol copolymer; polybutene; polybutylene terepthatlate, poly-cinene, polyethylene; polyisobutene; polyisoprene, polyvinyl butyral, polyethylene laurate; the propane diols dicaprylate; propane diols two cocounut oil acid esters, propane diols two different pelargonates, propane diols dilaurate; propylene glycol dipelargonate; the two stearates of propane diols, the two hendecane acid esters of propane diols, PVP/ eicosylene copolymer; PVP/ hexadecene copolymer; rice bran wax, oronain bentonite (stearalkonium bentonite) draws in department, and oronain hectorite (stearalkonium hectorite) draws in department; stearmide; the two stearates of stearmide DEA-, stearmide DIBA-stearate, stearmide MEA-stearate; stearone; octadecanol, stearoyl mustard acid amides, stearyl stearate; stearyl stearyl stearate; synthetic bees wax, synthetic paraffin, three hydroxyl stearins; three different ninth of the ten Heavenly Stems essence; three different stearins, three isooctadecanol trimerized linoleic acid esters, trilaurin; trimerized linoleic acid; trilinolein, myristin, triolein; tripalmitin; glyceryl tristearate, zinc laurate, Zinc tetradecanoate; zinc neodecanoate; abietic acid zinc, zinc stearate and its mixture.

[00142] the exemplary gelling agent that uses in the present invention including, but not limited to:

Polyethylene glycol ﹠ propane diols ﹠ water	(ACULYN 44)
		Acrylic acid dimethyl taurine ammonium/VP copolymer	(ARISTOFLEX AVC)
Glyceryl Ying Zhisuanzhi ﹠PEG100 stearate	(ARLACEL 165)
		Polyethylene (2) stearyl ether	(BRIJ 72)
Polyoxyethylene (21) stearyl ether	(BRIJ 721)
		Silica	(CAB-O-SIL)
Polyquaternium10	(CELQUAT CS230M)
		Cetanol
Cetostearyl alcohol ﹠ ceteareth 20	(COSMOWAX P)
		Cetostearyl alcohol ﹠ dicetyl phosphate ﹠ cetanol polyethers-10 phosphate	(CRODAFOS CES)
Cetanol polyethers-20 phosphate ﹠ cetostearyl alcohol ﹠ dicetyl phosphate	(CRODAFOS CS-20 Acid)
		Cetostearyl alcohol ﹠ ceteareth 20	(EMULGADE NI 1000)
Sodium silicate magnesium	(LAPONITE XLG)
		Cetanol ﹠ octadecanol ﹠ stearyl dimethyl benzyl ammonium chloride (Stearalkonium Chloride) ﹠ dimethyl stearylamine ﹠ lactic acid	(MACKADET CBC)
Cetostearyl alcohol stearamide propyl dimethyl amine stearoyl amido propyl-dimethyl benzyl ammonium chloride (Stearamidopropyl alkonium chloride)	(MACKERNIUM Essential)
		Stearyl dimethyl benzyl ammonium chloride (Stearalkonium chloride)	(MACKERNIUM SDC-85)
Cetostearyl alcohol stearamide propyl dimethyl amine stearoyl amido propyl-dimethyl benzyl ammonium chloride (Stearamidopropylalkonium chloride) siloxanes Quaternium16	(MACKERNIUM Ultra)
		Cetostearyl alcohol ﹠ cetostearyl alcohol glucoside	(MONTANOV 68EC)

Hydroxyethylcellulose	(NATROSOL 250HHR CS)
		Polyquaternium-37﹠ mineral oil ﹠ tridecanol polyethers-6	(SALCARE SC 95)
Polyquaternium-32﹠ mineral oil ﹠ tridecanol polyethers-6	(SALCARE SC 96)
		Stearic acid
The cetyl hydroxyethylcellulose	(NATROSOL Plus330CS)
		Polyvinyl alcohol, PVP-K30, propane diols
Stearic acid, docosyl alcohol, tristerin, lecithin, C12-16 alcohol, palmitic acid	(PROLIPID 141)
		Beeswax	(saponification beeswax)
Beeswax	(synthetic bees wax)
		Water, beeswax, sesame oil, lecithin, methyl p-hydroxybenzoate	(royal jelly)
Polyquaternium10	(CELQUAT SC240C)
		PAA/sodium acryloyldimethyl taurate copolymers ﹠ isohexadecane ﹠ polysorbate 80	(SIMULGEL EG)
Polyquaternium44	(LUVIQUAT Care)

[00143] in this composition, can have active antibacterial agent, if any, its quantity be composition about 0.001% to about 5% weight, preferably approximately 0.01% to about 2% weight, and more preferably about 0.05% to about 1% weight.

[00144] antimicrobial can be for example hydrogen peroxide or benzoyl peroxide, three halogenated diphenyl ureas, quaternary ammonium compound, ethoxylation phenol and a phenol type compound of biguanides (for example Chlorhexidine digluconate), diphenyl compounds, phenmethylol, peroxide for example, the phenolic compound that replaces of halogen for example, for example PCMX (promptly between chloro--xylenols) and triclosan (promptly 2,4,4 '-three chloro-2 '-dihydroxy diphenyl ether).The preferred optional antibacterial agent is following illustrational phenol and diphenyl compounds.

[00145] antibacterial agent that is used for the present invention is that compound by the following classification that is used singly or in combination comes illustrational:

(1) phenols antibacterial agent

(a) 2-hydroxydiphenyl compounds

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, and m is 0 or 1, and n is 0 or 1.

[00146] 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, and r is 1 or 2, and p is 0.

[00147] in particularly preferred embodiment, Y is a chlorine, and m is 0, and n is 0, and o is 1, and r is 2, and p is 0.

[00148] the 2-hydroxydiphenyl compounds that is particularly useful has following array structure:

Have generally acknowledged title triclosan, the coml trade name is IRGASAN DP300, is obtained from Ciba Specialty Chemicals Corp., Greensboro, NC.Another useful 2-hydroxydiphenyl compounds is 2,2 '-dihydroxy-5,5 '-two bromo-diphenyl ether.

(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 the sulphur of alkali metal salts or ammonium salt form; R ₄Be hydrogen or methyl; R ₅Be hydrogen or nitro.Halogen is a bromine, or preferred chlorine.

[00149] object lesson of phenol derivatives is including, but not limited to: chlorophenols (adjacent,, to), 2,4 dichloro benzene phenol, p-nitrophenol, picric acid, xylenols, between chloro--xylenols, cresols (adjacent,, to), to chloro-m-cresol, catechol, resorcinol, 4-n-hexyl resorcinol, pyrogallol, phloroglucin, carvacrol, thymol, to Chlorothymol, o-phenyl phenol, 2-methane, to the chlorine 2-methane, phenol, 4-ethyl phenol and 4-phenolsulfonic acid.Other phenol derivatives is listed in U.S. Pat 6,436, and in 885, this paper is introduced into as a reference.

(c) diphenyl compounds

Wherein X is sulphur or methylene, R ₆And R ' ₆Be hydroxyl, R ₇, R ' ₇, R ₈, R ' ₈, R ₉, R ' ₉, R ₁₀And R ' ₁₀Be hydrogen or halogen independently of one another.The concrete non-limitative example of diphenyl compounds is a hexachlorophene, tetra-chloro-phenol, antiphen, 2,3-dihydroxy-5,5 '-the dichloro diphenyl sulfide, 2,2 '-dihydroxy-3,3 ', 5,5 '-the 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 listed in U.S. Pat 6,436, and in 885, this paper is introduced into as a reference.

(2) quaternary ammonium antibacterial agent

[00150] effectively the quaternary ammonium antibacterial agent has following conventional structure formula:

R wherein ₁₁, R ₁₂, R ₁₃And R ₁₄In at least one be alkyl, aryl or the alkaryl substituting group that contains 6 to 26 carbon atoms.Perhaps, any two R substituting groups can combine with nitrogen-atoms, form 5 or 6 yuan of aliphatic or aromatic ring.Preferably, whole ammonium cations of antibacterial agent partly have at least 165 molecular weight.

[00151] substituent R ₁₁, R ₁₂, R ₁₃And R ₁₄Can be straight chain maybe can be a side chain, but straight chain preferably, and can comprise one or more acid amides, ether or ester bond.Especially, at least one substituting group is C ₆-C ₂₆Alkyl, C ₆-C ₂₆Alkoxy aryl, C ₆-C ₂₆The C that alkaryl, halogen replace ₆-C ₂₆Alkaryl, C ₆-C ₂₆The alkyl phenoxy alkyl, or the like.The substituting group that keeps outside the above substituting group on the quaternary nitrogen atoms typically contains and is no more than 12 carbon atoms.In addition, the nitrogen-atoms of quaternary ammonium antibacterial agent may reside in the ring system, both can be aliphatic for example piperidyl, also can be for example pyridine radicals of aromatic series.Anion X can be the anion that can make the water-soluble any formation salt of quaternary ammonium compound.Anion is including, but not limited to halogen, for example, and chloride, bromide or iodide, Methylsulfate and sulfovinate.

[00152] preferred quaternary ammonium antibacterial agent has following structural:

R wherein ₁₂And R ₁₃Be C independently ₈-C ₁₂Alkyl, or R ₁₂Be C ₁₂-C ₁₆Alkyl, C ₈-C ₁₈Alkyl ethoxy or C ₈-C ₁₈The alkyl phenyl ethyoxyl, R ₁₃Be benzyl, X is halogen, Methylsulfate, sulfovinate or tosilate.Alkyl R ₁₂And R ₁₃Can be straight or branched, straight chain preferably.

[00153] the quaternary ammonium antibacterial agent in this composition can be the mixture of single quaternary ammonium compound or two or more quaternary ammonium compounds.The quaternary ammonium antimicrobial that is particularly useful comprises dialkyl group (C ₈-C ₁₀) dimethyl ammonium chloride (for example, the dioctyl dimethyl ammonium chloride), zephiran (for example, benzalkonium chloride and myristyl dixylyl ammonium chloride), alkyl methyl dodecylbenzyl ammonium chloride, methyl dodecyl dimethylbenzene-two-trimethyl ammonium chloride, benzethonium chloride, the dialkyl methyl benzyl ammonium chloride, alkyl dimethyl ethyl ammonium bromide, and alkyl tertiary amine.In the present invention, also can use polymeric quaternary ammonium compound based on these monomer structures.An example of polymeric quaternary ammonium compound is

For example, 2-cyclobutenyl dimethyl ammonium chloride polymer.Above-mentioned quaternary ammonium compound can obtain with following trade name commercial:

With

Be obtained from supplier, Lonza for example, Inc., Fairlawn, NJ and Stepan Co., Northfield, IL.

[00154] other example of quaternary ammonium antibacterial agent is including, but not limited to alkyl ammonium halide, for example softex kw; Alkylaryl ammonium halide, for example octadecyl dimethyl benzyl ammonium bromide; N-alkyl halide pyridine, for example N-cetyl bromination pyridine; Or the like.Other suitable quaternary ammonium antimicrobial has acid amides, ether or ester moiety, Octylphenoxy ethoxyethyl group dimethyl benzyl ammonium chloride for example, and N-(lauryl cocoa base carbamyl ylmethyl) pyridinium chloride, or the like.The quaternary ammonium antibacterial agent of other classification comprises those that contain substituted aryl nuclear, for example, lauryl oxygen base phenyl trimethyl ammonium chloride, cetyl aminophenyl trimethyl methylsulfuric acid ammonium, dodecylphenyl trimethyl methylsulfuric acid ammonium, the dodecylbenzyl trimethyl ammonium chloride, chlorination dodecylbenzyl trimethyl ammonium chloride, or the like.

[00155] concrete quaternary ammonium antibacterial agent is including, but not limited to mountain Yu base dimethyl benzyl ammonium chloride (behenalkonium chloride), cetearyl dimethyl benzyl ammonium chloride (cetarylalkonium chloride), cetearyl dimethyl benzyl ammonium bromide (cetarylalkonium bromide), west bent ammonium toluene fulfonate (cetrimonium tosylate), hexadecylpyridinium chloride, Laura bromine ammonium, Lauralkonium Chloride, lapirium chloride, dodecyl chlorination pyridine, the myristyl dimethyl benzyl ammonium chloride, oil base dimethyl benzyl ammonium chloride and iso stearyl ethyl two ammonium chlorides (isostearyl ethyldimonium chloride).Preferred quaternary ammonium antimicrobial comprises benzalkonium chloride, benzethonium chloride, cetyl bromination pyridine and methyl benzethonium chloride.

(3) aniline and biguanides antibacterial agent

[00156] effectively aniline and biguanides antibacterial agent including, but not limited to neko, diphenylurea, the N-salicylaniline, Tribromsalan (tribromosalan), tetrachloro is for salicylaniline, Flusalan (fluorosalan), chlorhexidine gluconate, chlorhexidine hydrochloride and its mixture.

[00157] other specific category of optional components comprises inorganic phosphate, sulphate and the carbonate as buffer; EDTA and phosphate as chelating agent; With bronsted lowry acids and bases bronsted lowry as pH value conditioning agent.

[00158] example of the preferred classes of Ren Xuan alkaline pH value conditioning agent is an ammonia; List, two-and three-alkylamine; List, two-and three-alkanolamine; Alkali metal and alkaline earth metal hydroxide; With its mixture.Yet, do not limit the characteristic of alkaline pH value conditioning agent, and can use any alkaline pH value conditioning agent known in the art.Alkaline pH value conditioning agent concrete and non-limitative example is an ammonia; Sodium hydroxide, potassium hydroxide and lithium hydroxide; MEA; Triethylamine; Isopropanolamine; Diethanol amine; And triethanolamine.

[00159] example of the preferred classes of Ren Xuan acid ph value conditioning agent is an inorganic acid.The non-limitative example of inorganic acid is hydrochloric acid, nitric acid, phosphoric acid and sulfuric acid.Do not limit the characteristic of acid ph value conditioning agent, and can separately or be used in combination any acid ph value conditioning agent known in the art.

[00160] composition also can contain cosolvent or fining agent, for example has as many as about 4000 molecular weight polyethylene glycol, methyl propanediol, the oxidation solvent of ethene, propylene or butylene or its mixture.Can comprise cosolvent or fining agent as required,, and may reside in the residual film or layer of the lip-deep composition of handling so that give stability and/or clarity to composition.

[00161] provides the optional alkanolamide of thickening to be to composition but be not limited to: coconut oleoyl amine MEA, coconut oleoyl amine DEA, soybean oil acid amides (soyamide) DEA, lauramide DEA, oleamide MIPA, stearmide MEA, myristamide MEA, lauramide MEA, decyl amide DEA, castor oil acid amides DEA, myristamide DEA, stearmide DEA, oleamide DEA, tallow acid amides DEA, lauramide MIPA, tallow acid amides MEA, isostearoyl amine DEA, isostearoyl amine MEA and its mixture.Alkanolamide right and wrong clean surface activating agent, and if any, add on a small quantity, thereby make the composition thickening.F.pH

[00162] at 25 ℃, the pH value that contains this antimicrobial compositions of organic acid is less than about 5, preferably less than about 4.5.In order to obtain whole benefit of the present invention, the pH value is less than about 4.Typically, the pH value that contains this composition of organic acid is for about 2 to less than about 5, and preferably approximately 2.5 to about 4.5.

[00163] the pH value of composition should be low fully, so that at least a portion organic acid is a protonated form.Then, organic acid has the ability that reduces surface p H value, skin pH value for example, thus effective viral control is provided, can not make the skin discomfort.Organic acid also deposits on skin, and withstands flushing and remove, thereby lasting antiviral effect is provided.

[00164] the new and beyond thought result in order to prove that antimicrobial compositions of the present invention provides has prepared the following example, measures composition control Gram-positive and Gram-negative bacteria and the rhinoviral ability of control.The percetage by weight of listing in each the following example is represented reality or the active weight that is present in component in the composition.According to those skilled in the art understood with as described below,, component prepares composition by being mixed.

[00165] in the preparation of embodiment and test, use following method:

[00166] a) measures quick sterilization (time limit deactivation) activity of antibacterium product.Utilize the time limit deactivation method, measure the activity of antibacterial compositions, measure the survival rate of the organism under fire that contacts with the antibacterium subject composition thus with function of time form.In this test, under set point of temperature, the dilution aliquot sample that makes composition contacts preset time with known test bacterial population.At the terminal point in this period, neutralization test composition, antibacterial activity that can composite inhibiting.The percentage or the logarithm that calculate the primitive bacteria population reduce.

[00167] common, the time limit deactivation method is known for those skilled in the art.

[00168] can any under 100% concentration subject composition.The selection of working concentration is the judgement according to the researcher, and those skilled in the art determine suitable concn easily.For example, the sample of thickness is tested under 50% diluting condition usually, and noncohesive sample need not dilute.Test specimen is placed in the aseptic 250ml beaker that is equipped with magnetic stirring bar, if necessary, sample volume is transferred to 100ml with aseptic deionized water.Carry out all tests in triplicate, the result is merged, report that average logarithm reduces.

[00169] also researcher's processing at one's discretion of the selection in stage time of contact.Can select any stage time of contact.Typical time of contact is 15 seconds to 5 minutes scope, and is typical time of contact in 30 seconds and 1 minute.Contact temperature also can be any temperature, room temperature, or about 25 Celsius temperatures typically.

[00170] prepares bacterial suspension or test inoculum by go up the cultivation bacterial cultures at any suitable solid culture medium (for example agar).Wash out bacterial population with stroke-physiological saline solution from agar then, and the population of bacterial suspension is adjusted to every ml about 10 ⁸Colony-forming units (cfu/ml).

[00171] following table has been listed employed in test test bacterial cultures, comprises the title of bacterium, ATCC (American Type Culture Collection) identification number and the hereinafter title abbreviation of the organism of use.Staphylococcus aureus (S.aureus) is a Gram-positive bacteria, and Escherichia coli (E.coli), Friedlander (K.pneum) and Salmonella choleraesuls (S.choler.) they are Gram-negative bacterias.

The organism title	ATCC #	Abbreviation
			Staphylococcus aureus	6538	S.aureus
Escherichia coli	11229	E.coli
			Friedlander	10031	K.pneum.
Salmonella choleraesuls	10708	S.choler.

[00172] beaker that will contain subject composition is placed on (if expectation constant temperature) in the water-bath, or puts (if wanting the environmental experiment room temperature) on the magnetic stirring apparatus.Then to sample inoculation 1.0ml test bacterial suspension.Inoculum and subject composition are stirred predetermined time of contact.When stop time of contact, subject composition/bacterial mixture of 1.0ml is transferred in the 9.0ml neutralizer solution.Carry out decimal dilution then, to isarithmic scope.The dilution of different organisms can be different.Selected dilution is coated in (TSA+ is the tryptic soy agar that has lecithin and polysorbate 80) on the TSA+ plate in triplicate.Then plate was cultivated 24 ± 2 hours,, and calculated percentage or logarithm minimizing for bacterium colony survivor's number counting.Determine control group counting (contrast quantity) by operating aforesaid method, not existing together is that subject composition is replaced with deionized water.The plate count that will contrast quantity and sample size by the standard microorganism determination method respectively changes cfu/ml into.

[00173] using following formula to calculate logarithm reduces:

Logarithm minimizing=log ₁₀(contrast quantity)-log ₁₀(test specimen survival).

[00174] following table is associated the minimizing of the percentage in the bacterial population with the logarithm minimizing:

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

[00175] antiviral residual effect test b)

[00176] list of references: S.A.Sattar, Standard Test Method forDetermining the Virus-Eliminating Effectiveness of Liquid HygienicHandwash Agents Using the Fingerpads of Adult Volunteers, Annual Bookof ASTM Standards.Designation E1838-96, all be incorporated herein as a reference with it, and be called ＂ 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, Vol.59, No.5, May, 1993, pp.1579-1585 all is incorporated herein as a reference with it, and is called ＂ Sattar II ＂.

[00177] method that is used for measuring the antiviral index of the present invention is to be described in improving one's methods of Sattar I (a kind of test that is used for the liquid hand with the viricidal activity of washings (rinsing out product)).In this case, this method is modified, so that the authentic data of conservative product is provided.

[00178] improving one's methods of Sattar I comprises directly to skin and product as described below is provided, carries out the virus inoculation of finger pad and use ten circulation cleanings to reclaim virus according to as described below.By handling this zone, the inoculation skin site is thoroughly purified then with the dilution of the ethanol in 70% water.

[00179] method:

Test in [00180] ten minute:

[00181] the non-medicated soap washing experimenter's of initial usefulness (5 of each test products) hand, the flushing hand makes the hand drying.

[00182] uses 70% Ethanol Treatment hand, air drying then.

[00183] test products (1.0ml) is applied to hand, except that thumb, makes the hand drying.

[00184] in about 10 minutes (± 30 second) after the products applied, uses micro-pipette, with 10 μ l rhinoviruss, 14 suspension (ATCC VR-284, about 1 * 10 ⁶PFU (plaque-forming unit)/ml) part is applied to the long-pending interior a plurality of sites of the skin surface that is called as finger pad on hand.At this moment, by similar mode, rhinovirus solution also is applied to untreated thumb.

[00185] after dry 7-10 minute, virus is eluted each site washing 10 times from each skin site with 1ml washing lotion (Earle ' s balanced salt solution (EBSS) contains 25% fetal bovine serum (FBS)+1% pen-strep-glutamate).

[00186], the inoculation skin site is purified fully then by washing with 70% ethanol.Use standard technique, i.e. plaque method or TCID ₅₀(TCID) measures virus titer.

Test in [00187] one hour:

[00188] between 1 hour and 3 hours time points, make the experimenter recover normal behaviour (except the hand that washs them).After one hour, rhinovirus suspension is applied to the site of appointment on the finger pad, and elutes from it, as described in testing as top 10 minutes fully.

[00189] embodiment 1-10 and 13 for example understands the ability of this composition control bacterium and virus.For example clear this composition maintenance of embodiment 11 and 12 is moistening and stop pure ability of evaporating, and has prolonged the anti-bacterial effect and the mildness that has improved composition of composition thus.Be also to be noted that and add the apparent flash-point that cetearyl alcohol pure and mild ceteareth-20 blend has improved this composition.For example, contain the composition flash-point of composition of 62% weight ethanol by being increased to 95 ℉ less than 80 ℉.

Embodiment 1

[00190] 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

[00191] in time limit deactivation suspension test specimen at the antiviral activity of rhinovirus 1A and rotavirus Wa.Following table has been summed up result of the test.

[00192] the synergistic corrosion virus effect that provides by sterilize alcohol and the organic acid coupling that has less than one log P has been provided this embodiment.Sample A and B show that independent sterilization alcohol does not provide acceptable virus control.Sample E shows that the salicylic acid that is dissolved in dipropylene glycol and the water can not make test virus serotype inactivation up hill and dale.Yet, sample C and D, it is a composition of the present invention, can eliminate the test virus serotype up hill and dale.

Embodiment 2

[00193] preparation can reduce the following antiviral composition of skin pH value, and is applied on the finger pad of human volunteer:

¹⁾Acrylate/C10-30 alkyl acrylate cross-linked copolymer

²⁾Preservative contains propane diols, diazonium imidazolidinyl urea, methyl p-hydroxybenzoate and nipasol.

The pH value of sample 2 is 3.1.

[00194] in this test, sample 2 is applied to the finger pad of all fingers of eight volunteers, except the thumb.Thumb is a control site.The volunteer is divided into four groups, every group of two volunteers.Be titrated to rhinovirus at the fixed time then and attack the I-IV group on all finger pad of each hand, thereby the time of determination test composition relies on effect.When each combination is suitable, also measures the skin pH value of finger pad, thereby measure the time course of skin pH value for the subject composition response.For the I-IV group, rhinovirus is attacked and the presumptive test time of skin pH pH-value determination pH is respectively 5 minutes, 1 hour, 2 hours and 4 hours.Average log (the rhinoviral titre of inoculation), mean skin pH value and the average log (the rhinoviral titre of recovery) that is obtained from volunteer's test finger pad in the research summed up in following tabulation, works out with group.

Group	Initial skin pH value (mean value) after using	The skin pH value (mean value) of testing time	Log[inoculum titre] (mean value)	Log[reclaims titre] (mean value)
					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

[00195] data of each group (being different time points) show, the average rhinovirus titre of recovering is less than 1 virion, or are lower than the detectability of test.This data declaration the effect of this method after 4 hours, and show further that eliminating fully aspect the virus attack, skin pH value is effective less than about 4.The coupling of citric acid, malic acid and polymeric acid (promptly 20) can on finger pad, provide residual organic acid barrier layer, but the permanent disease-resistant cytotoxic activity of this enhancing composition.

[00196] in another skin pH value test, the amount of malic acid among the amount of citric acid among the embodiment 2 and the embodiment 2 is increased to 5% weight separately, and cuts the corresponding water yield.The composition that obtains has 25 ℃ of pH values of about 2.38 down.It is found that and improve organic acid total amount to 20% weight, cause phase instability.

Embodiment 3

[00197] with the cleaning finger pad of following compositions-treated subjects.Before with compositions-treated, measure baseline skin pH value registration by finger pad.Composition after the drying, is measured skin pH value immediately on finger pad, after four hours, measure once more.

Sample	Composition (wt%)	Mean skin pH value (T=0)	Mean skin pH value (T=4hr)	Virus Log10 reduces	The hand % that has virus
						A	2% citric acid, 2% malic acid, 62%ETOH, 1.25% hydroxyethylcellulose	2.81	3.23	>3 log 10	0
B	2% citric acid, 2% tartaric acid 62%ETOH, 1.25% hydroxyethylcellulose	2.64	3.03	>3 log 10	0
						C	2% malic acid, 2% tartaric acid, 62% ETOH, 1.25% hydroxyethylcellulose	2.66	2.94	>3 log 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	>3 log 10	0
F	70%ETOH, 1% polyacrylic acid	4.80	5.16	2.0 log 10	100
						G	70%ETOH, 1.25% hydroxyethylcellulose	5.3	5.25	<0.5 log 10	100

¹⁾ETOH is an ethanol

[00198] with sample A-G handle after the finger pad four hours with rhinovirus 39 with 1.3 * 10 ³The titre of pfu (plaque-forming unit) is applied to finger pad.With virus on finger pad dry 10 minutes, wash finger pad with containing 75% EBSS and 25% FBS and 1 * antibiotic viral withdrawal liquid medium then.With sample serial dilution in viral withdrawal liquid medium, and be coated on the H1-HeLa cell according to plaque method mensuration titre.The composition that contains acid that use contains two mixture in citric acid, malic acid and the tartaric acid obtains the complete deactivation of rhinovirus 39, promptly reduces greater than 3 logarithm.

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 skin soft agent

[00199] this embodiment explanation, composition of the present invention also provides fast and the wide spectrum antibacterial activity.

Embodiment 5

[00200] with the cleaning finger pad of following compositions-treated subjects.Before with compositions-treated, measure baseline skin pH value registration by finger pad.Composition after the drying, is measured skin pH value immediately on finger pad.

[00201] with after the compositions-treated finger pad immediately with rhinovirus 14 with 1.4 * 10 ⁴The titre of pfu (plaque-forming unit) is applied on the finger pad.With virus on finger pad dry 10 minutes, wash finger pad with containing the antibiotic viral withdrawal liquid medium of 75% EBSS and 25% FBS and 1X then.With sample serial dilution in viral withdrawal liquid medium, and be coated on the H1-HeLa cell according to plaque method mensuration titre.With the complete deactivation of acid-containing composition acquisition rhinovirus 14, cause 4 logarithm minimizing.

Sample	Composition (wt%)	The pH value of solution value	30 seconds, virus Log10 reduced	The hand % that has virus
					A	2% citric acid, 2% malic acid, 70%ETOH, 1% polyacrylic acid	3.10	4log	0

Embodiment 6

[00202] prepare following composition, test organic acid and organic acid mixture are for the effect of skin pH value and antiviral effect.

Sample	Composition (wt%)	Mean skin pH value (T=0)	Mean skin pH value (T=2 hr)	Virus Log10 reduces
					A	4% citric acid is in 70% ethanol/water	2.97	3.64	>3 log 10
B	4% malic acid is in 70% ethanol/water	2.91	3.94	>3 log 10
					C	2% citric acid and 2% malic acid are in 70% ethanol/water	2.99	3.38	>3.log 10
D	4% tartaric acid is in 70% ethanol/water	2.56	3.0	>3 log 10

[00203] the cleaning finger pad of usefulness sample A-D Processing Test object.Before with compositions-treated, measure baseline skin pH value registration by finger pad.Composition after the drying, is measured skin pH value immediately on finger pad, after two hours, measure once more.

[00204] all samples A-D suppresses skin pH value to being lower than 4, keeps two hours.The coupling of citric acid and malic acid (sample C) has kept in two hours than using the low pH value of same acids (sample A and B) separately.4% tartaric acid composition (sample D) has shown that the maximum of skin pH value suppresses.

[00205] with latter two hour of solution-treated finger pad, with rhinovirus 39 with 4 * 10 ⁴The titre of pfu is applied on the finger pad.With virus on finger pad dry 10 minutes, wash finger pad with containing 75% EBSS and 25% FBS and 1 * antibiotic viral withdrawal liquid medium then.With sample serial dilution in viral withdrawal liquid medium, and be coated on the H1-HeLa cell according to plaque method mensuration titre.Obtain the complete deactivation of rhinovirus 39, cause logarithm to reduce greater than 3.

[00206] the following example explanation, in the presence of alcohol, polymeric acid, particularly acrylate homopolymer or copolymer can be given antiviral effect.Polymeric acid have low pH value and with the good substantivity of skin, As time goes on, it can keep low skin pH value effectively, and help provides lasting antiviral effect.

[00207] in the presence of alcohol, use acrylic acid based polymer, can show for the synergistic effect that reduces skin pH value.Yet under the situation that does not have alcohol, As time goes on, the skin pH value that acrylic acid based polymer can not keep reducing reaches identical degree.Importantly, when being used in combination polymeric acid with alcohol, composition pH value is not too depended in the reduction of skin pH value.The synergy that shows between polymeric acid and alcohol is beyond thought, and provides the new method of the skin pH value of reduction, and the skin ph value of described reduction provides the antiviral effect of expectation.

[00208] when being used in combination acrylic acid based polymer, also shown synergistic effect for quick and permanent disease-resistant cytotoxic activity with polybasic carboxylic acid.Have been found that with polybasic carboxylic acid for example citric acid, malic acid, tartaric acid and its mixture use the polymeric acid (for example about 0.1% to about 2% weight) of low quantity, can strengthen the antiviral activity of polybasic carboxylic acid.This synergistic effect allows to reduce the polybasic carboxylic acid concentration in the antiviral composition, and the reduction of antiviral effect can not take place.This reduction of polybasic carboxylic acid concentration can improve the soft property of composition by the potential stimulus that reduces composition.In theory, rather than according to this paper, polymeric acid help on handles surface the formation residual barrier film of organic acid or layer, the permanent disease-resistant cytotoxic activity that this can enhancing composition.

Embodiment 7

[00209] in 70% ethanol water and water, preparation contains the composition of polyacrylic acid (1%wt) (be ULTREZ 20, be obtained from Noveon Europe).Each composition (1.8ml) is applied to thumb, forefinger and the middle finger of subjects.Measure skin pH value registration before in processing (benchmark), measure immediately after the dry fingers, after two hours, measure once more.Below mean skin pH value reading is summarized in.

[00210] beginning, extremely after about 4.5, two hours, skin pH value remains on below 5 polyacrylic acid inhibition skin pH value.The skin pH value (4.4) that composition suppressed that contains ethanol is a little less than the composition that does not contain ethanol (4.5).This result represents when polyacrylic acid is used with ethanol, to have synergistic effect to reducing skin pH value.

[00211] with latter two hour of above-mentioned compositions-treated finger pad, with rhinovirus 39 with 9.8 * 10 ²The titre of pfu is applied on the treated finger pad.With virus on finger pad dry 10 minutes, wash finger pad with viral withdrawal liquid medium then.With liquid nutrient medium serial dilution in viral withdrawal liquid medium, and be coated on the H1-HeLa cell according to plaque method mensuration titre.Two kinds of compositions all can reduce virus titer.Yet, comparing with the composition that does not contain ethanol (reducing titre 1.5log), the composition (reducing titre 1.8log) that contains ethanol demonstrates bigger slightly effect at rhinovirus.

[00212] this data declaration, polyacrylic acid can suppress skin pH value, cause antiviral effect.These data illustrate that also polyacrylic acid and ethanol can reduce skin pH value synergistically, cause thus at rhinoviral bigger effect.

[00213] for this effect is described, prepare following eight kinds of compositions, wherein will contain polyacrylic solution (have and do not have ethanol) and be buffered to about 4.5,5.0,5.5 or 6.0 pH value.

Sample	Composition (wt%)	The pH value of solution value	Mean skin pH value 2hrs.	Virus Log 10Reduce
					A	1% ULTREZ, 20/70% ethanol	4.54	4.52	>2 log 10
B	1% ULTREZ, 20/70% ethanol	5.10	4.87	>2 log 10
					C	1% ULTREZ, 20/70% ethanol	5.54	4.41	>2 log 10
D	1% ULTREZ, 20/70% ethanol	6.17	4.32	>2 log 10
					E	1％ ULTREZ 20	4.57	4.93	<1 log 10
F	1％ ULTREZ 20	5.12	5.46	<1 log 10
					G	1％ ULTREZ 20	5.55	5.33	<1 log 10
H	1％ ULTREZ 20	6.32	5.70	<1 log 10

[00214] eight kinds of compositions of test are to the effect of skin pH value and viral effect.Every kind of composition (1.8ml) is applied to thumb, forefinger and the middle finger of subjects.Before handling, measure skin pH value registration (benchmark), measure immediately after the product drying, after two hours, measure once more.

[00215] skin pH Value Data shows, polyacrylic acid and ethanol can suppress skin pH value synergistically, because can suppress skin pH value to lower value than the composition that does not contain ethanol comprising with every kind of composition with ethanol that polyacrylic acid combines.Contain ethanol and polyacrylic composition and can reduce skin pH value between pH value 4 and 5, irrelevant with the pH value of solution value.On the contrary, the composition that does not contain ethanol only suppresses skin pH value between the pH value 5-6, and final skin pH value is similar to the pH value of solution value.

[00216] in order to test the viral effect of above-mentioned composition, after two hours, with rhinovirus 39 with 1.7 * 10 ³The titre of pfu is applied on the finger pad.With dry 10 minutes of virus, wash-out and serial dilution in viral withdrawal liquid medium.Sample is coated on the H1-HeLa cell, and measures virus titer according to the plaque method.The composition that contains the ethanol that combines with polyacrylic acid, virus titer have greater than 2 logarithm and reduce, and the compositions display that does not contain ethanol goes out virus titer and reduces less than 1 logarithm.Therefore, aspect reduction skin pH value, have synergistic effect between polyacrylic acid and the ethanol, this can provide bigger antiviral efficacy at rhinovirus.In theory, rather than according to this paper, ethanol helps to provide more continuous film of organic acid or layer on skin, for example, by reducing the compositions table surface tension, helps composition more balanced and be administered to the surface equably especially on the skin.

Embodiment 8

[00217] prepares following composition, to further specify the antiviral effect that polyacrylic acid is provided.

Sample	Composition (wt%) thickener	The pH value of solution value	Mean skin pH value 2 hrs.	The hand % that has virus
					A	1% polyacrylic acid	4.21	4.7	63％
B	5.5% CRODAFOS acid 1)	5.41	5.0	100％
					C	1.25％ NATROSOL 250HHR CS 2)	6.32	5.3	100％

¹⁾CRODAFOS CS20 acid is cetanol polyethers-20 ﹠amp; Cetyl Alcohol (Cetaryl Alcohol) ﹠amp; Dicetyl phosphate; With

²⁾NATROSOL 250HHR CS is a hydroxyethylcellulose.

[00218] sample A-C (1.8ml) is applied to thumb, forefinger and the middle finger of cleaning.Before handling, obtain skin pH value registration (benchmark), obtain immediately after the dry fingers,, after two hours, obtain once more,, obtained once more afterwards in four hours for sample C for sample A and B.The mean value of skin pH value is provided in the above-mentioned table.

[00219] contain polyacrylic sample A and can reduce skin pH value to maximum degree, the final skin pH value after two hours is pH 4.7.Sample B and sample C can not be reduced to pH below 5.0 with skin pH value.This data show that polyacrylic acid has the skin pH value of inhibition and keeps low at least two hours ability of skin pH value.

[00220] goes back the viral effect of test specimen A-C at rhinovirus 39.With about 10 ³The virus loads of pfu is coated on thumb, forefinger and the middle finger of each hand of handling, and dry 10 minutes.Point with viral withdrawal liquid medium flushing then, and the serial dilution sample, be coated on the H1-HeLa cell.Use the plaque method to measure virus titer.For sample B and C, 100% hand is the rhinovirus positive, and this shows that these compositions are very little at rhinoviral effect.On the contrary, sample A has shown viral effect, because find that only 63% hand is the rhinovirus positive.

Embodiment 9

[00221] embodiment 7 shows that have synergistic effect between polyacrylic acid and the ethanol, this has caused the inhibition and the antiviral effect of skin pH value.Prepare following composition, the validity of check polybasic carboxylic acid mixture and single polycarboxylic acid compositions enantiopathy toxic effect fruit, every kind of composition combines with polyacrylic acid and ethanol.Preferred antiviral composition contains organic acid minimum number, that demonstration permanent disease-resistant toxic effect really requires.

[00222] composition is applied on the finger pad of cleaning hand.Shown in after the time, with about 10 ³To 10 ⁴The rhinovirus 39 of pfu is applied on hand, dry 10 minutes.By recovering virus with viral withdrawal liquid medium flushing hand.Then with sample serial dilution in viral withdrawal liquid medium, and be coated to and use the plaque method to measure virus titer on the H1-HeLa cell.Below the percentage of the hand of the rhinovirus positive is summarised in.

Composition (wt%)	Time	The hand % of the rhinovirus positive
			70% ethanol	15min.	100％
1% citric acid/1% malic acid/10% ethanol/water	1hr.	100％
			1% polyacrylic acid/4% citric acid/70% ethanol/water	4hrs.	91％
1% polyacrylic acid/1% citric acid/1% malic acid/70% ethanol/water	4hrs.	0％

[00223] containing the composition of 70% ethanol separately can not be effectively as antiviral composition.After one hour, citric acid (1%) and malic acid (1%) have lost effect at rhinovirus, because find that 100% hand is the rhinovirus positive.On the contrary, when the composition that contains 1% citric acid and 1% malic acid combines with polyacrylic acid and 70% ethanol when being applied on hand, after four hours, do not detecting virus on hand.The single acid that combines with polyacrylic acid and ethanol (4% citric acid) is less at rhinoviral effect, because after four hours, finds that 91% hand is the rhinovirus positive.

[00224] this data show is used polyacrylic acid and ethanol to allow to use the polybasic carboxylic acid of low concentration, thereby is obtained the target antiviral effect.This raising is at least in part owing to form organic acid residual film or layer on skin.

Embodiment 10

[00225] in composition, uses polyacrylic acid and ethanol skin pH value can be suppressed to and be lower than the pH value of solution value, as shown in embodiment 7.Whether the antiviral composition that contains citric acid, malic acid, polyacrylic acid and ethanol can be buffered to higher pH value of solution value and the skin pH that is equal to or less than pH4 is provided value in order to test, thereby obtain lasting antiviral activity, prepared following composition.

Sample	Composition (wt%)	The pH value of solution value	Initial skin pH value	4 hours skin pH value	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

[00226] composition (1.8ml) is applied to thumb, forefinger and the middle finger that cleans hand.Before handling, measure skin pH value registration (benchmark), measure immediately after the dry fingers, after four hours, measure once more.The mean value of skin pH value is demarcated in the above.

[00227] the initial skin pH value of sample skin that A-C handles is suppressed between pH 2.9 and 3.6, and wherein low more, the initial skin pH of pH value of solution value value is low more.Yet after four hours, for all three kinds of compositions, skin pH value is approximately pH3.7.Consistent with previous embodiment, the pH value of solution value does not indicate skin pH value subsequently.

[00228] same, test specimen A-C is at the viral effect of rhinovirus 39.With about 10 ³The virus loads of pfu is coated on thumb, forefinger and the middle finger of each hand of handling, and dry 10 minutes.Point with viral withdrawal liquid medium flushing then, and the serial dilution sample, be coated on the H1-HeLa cell.Use the plaque method to measure virus titer.From any virus that is not recovered on hand, show that three all sample A-C have antiviral effect.This raising is at least in part owing to form organic acid residual film or layer on skin.

[00229] this data show, when in composition, being used in combination citric acid and malic acid with polyacrylic acid and ethanol, can be buffered to the pH value of solution higher, for example, be administered to the softer and safer pH value of skin, also keep the ability that suppresses skin pH value and show antiviral activity simultaneously.This result is also at least in part because the evaporation of volatile compositions component remains on organic acid residual layer or the film on the skin afterwards.

[00230] following test shows, composition of the present invention can provide continuous basically organic acid barrier layer on the processing surface.Especially, following test shows, this composition is withstood the flushing to handle surface, for example after three flushings, measure according to NMR and IR spectrum, at least 50% non-volatile composition component (comprising organic acid) remain on handle on the surface.In addition, after 10 flushings, the effective antiviral quantity of non-volatile composition component remains on institute and handles on the surface, also uses NMR and IR to compose mensuration.

[00231] below in the test, will contain 2% malic acid, 2% citric acid, 1% polyacrylic acid, 62% ethanol and 0.5% hydroxyethylcellulose by weight and compare with the Aquo-composition (composition B) that contains 2% malic acid, 2% citric acid and 62% ethanol as the Aquo-composition (composition A) of gelling agent.Composition is applied to glass surface, film is provided.Infrared (IR) and nuclear magnetic resonnance (NMR) by the film that obtains after each flushing are composed as can be known, and after the water flushing once, composition B can be rinsed out from the surface fully.Therefore composition B fails to demonstrate water-resistance, and the film or the layer of the non-volatile composition component of failing to provide from the teeth outwards.

[00232] opposite, IR and NMR stave are bright, and composition A provides the film or the layer of the anti-flushing of composition component on the processing surface.Through the junior three time flushing, the amount reduction of the composition component that keeps on the processing surface in flushing subsequently, can withstand from the lip-deep further removal of handle then.IR and NMR stave are bright, after the flushing of 10 water, can detect non-volatile composition component with effective dose remain on handle on the surface.

[00233] carries out another test, measure the contact angle that water is gone up on the surface." contact angle " is to measure the yardstick that the wettability of water is gone up on the surface.In this test, composition A and B are applied on the glass surface drying.Then, measure contact angle with the glass of composition A and B processing (do not wash and use deionized water rinsing).Also measure the contact angle of exposed (promptly being untreated) glass, in contrast.Following table has been summed up the result of contact angle test.

	Composition A, not flushing	Composition A, flushing	Composition B, not flushing	Composition B, flushing	Exposed glass
						Average reading (degree)	45.96	72.66	6.69	41.51	38.47
The variation of the number of degrees		26.7		34.8
						Change %		58.1		520.2

[00234] the contact angle data show, composition A can modify glass surface, and lasting barrier film or layer is provided on glass surface.These data show that also composition B is rinsed from the surface, and the contact angle with exposed glass is identical basically because wash composition B contact angle afterwards.

[00235] carries out another test, with the absorption of the residual film of proof composition A to metal ion.In this test,, dry 4 hours at least, be exposed to then in the solution with 0.5M concentration of metal ions at the film of formation composition A on glass.Then by SEM scanning analysis sample.Data in the table show below, and the film that is produced by composition A combines the several types metal ion effectively.In theory, rather than according to this paper, this is a kind of superficial phenomenon, because the mechanism that metal ion is transported in the film is unknown.

[00236] also obtained the reflection micrograph (Fig. 1) that shows the surface coverage of composition A and B.The micrograph of enclosing shows that composition A provides basically surface coverage completely, and promptly composition A has more balanced coverage on the processing surface, and this just can provide the continuous basically layer or the film of non-volatile composition component from the teeth outwards.The micrograph of enclosing is the digital translation of reflected value, and it provides the directly related property with surface coverage.Micrograph shows, with composition B (Fig. 1 c) and 1d)) compare composition A (Fig. 1 a) and 1b)) can provide have high-adhesiveness, film that dispersiveness and crystal form.

[00237] rapid evaporation of the alcohol in the antimicrobial compositions has limited the lasting antimicrobial acivity of alcohol.Because alcohol is ethanol kill microorganisms in contact for example, by keeping moistening and the evaporation of prevention alcohol, bactericidal composition can provide the antimicrobial control of prolongation.The following examples show, add cetearyl alcohol pure and mild ceteareth-20 blend and can improve the moisture retention that contains pure antimicrobial compositions when being exposed to surrounding air.

Embodiment 11

[00238] other bacterium and fungi are carried out the time inactivation test, with the wide spectrum effect of the proof present composition.In this test, test following antimicrobial compositions.

Component	Percetage by weight
		Cetanol	1.00
Glycerine	1.00
		Isopropyl palmitate	1.00
Dimeticone 100CST	1.02
		Ethanol SDA-40B	3.09
Natrosol 250HHX	0.26
		Deionized water	10.94
Deionized water	17.65
		The ULTREZ10 polymer	1.01
Ethanol SDA-40B	58.82
		Citric acid	2.00
Malic acid	2.00
		Sodium hydroxide 50%	0.22

[00239] under following condition, the test above-mentioned composition is controlled the ability of following microorganism:

Test macro:	Staphylococcus aureus ATCC 6538 Escherichia coli ATCC 11229 listerisa monocytogenes in mjme (listeria monocytogenes) ATCC 7644 enterobacter cloacae ATCC 13047 Candida albicans ATCC 10231
		Test temperature:	Environment (20-25 ℃)
Time of contact:	15 and 30 seconds
		Neutralizer	99mL D/E liquid nutrient medium carries out the neutralizer screening as the part of test, confirms neutralizer neutralized product fully, and it is unfavorable can not to cause for the test organism body.
The successive transfer culture medium:	D/E agar
		Cultivate:	35 ± 2 ℃, 48 ± 4 hours (for staphylococcus aureus, Escherichia coli, listeria monocytogenes) 30 ± 2 ℃, 48 ± 4 hours (for enterobacter cloacae) 26 ± 2 ℃, 72 ± 4 hours (for Candida albicans)

[00240] test data is summarized as follows:

Inoculum quantity (CFU/mL)

Test macro	A	B	Mean value
				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
				Listerisa monocytogenes in mjme ATCC 13047	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
				Candida albicans ATCC 10231	24 x 10 5	26 x 10 5	2.5 x 10 6

Staphylococcus aureus ATCC 15442

Time of contact (second)	Survival (CFU/mL)	Average survival (CFU/mL)	Logarithm reduces	Percentage reduces
					15	<100，<100	<100	>5.48	>99.999
30	<100，<100	<100	>5.48	>99.999

Escherichia coli ATCC 11229

Time of contact (second)	Survival (CFU/mL)	Average survival (CFU/mL)	Logarithm reduces	Percentage reduces
					15	2 x 10 2，<100	<1.5 x 10 2	>5.08	>99.999
30	<100，<100	<100	>5.26	>99.999

Listerisa monocytogenes in mjme ATCC 7644

Time of contact (second)	Survival (CFU/mL)	Average survival (CFU/mL)	Logarithm reduces	Percentage reduces
					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

Time of contact (second)	Survival (CFU/mL)	Average survival (CFU/mL)	Logarithm reduces	Percentage reduces
					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

Candida albicans ATCC 10231

Time of contact (second)	Survival (CFU/mL)	Average survival (CFU/mL)	Logarithm reduces	Percentage reduces
					15	<100，<100	<100	>4.40	>99.996
30	<100，<100	<100	>4.40	>99.996

[00241] these data show, 15 and 30 seconds time of contact, the present composition demonstrates about logarithm of 4 to 5 at staphylococcus aureus ATCC 6538, Escherichia coli ATCC 11229, monocyte Listeria monocytogenes ATCC 7644, enterobacter cloacae ATCC 13047 and Candida albicans ATCC10231 to be reduced.

[00242] data show above, contain this antimicrobial compositions of organic acid and also can effectively control fungi, comprise saccharomycete and mould.Fungi control is important, because fungi can cause many plant and animal diseases.For example, in the mankind, fungi can cause other serious disease of tinea, the ringworm of the foot and some.Because fungi is more similar to animal with genetic aspect at chemistry than other organism, so mycosis is to be difficult to treatment.Correspondingly, the prevention mycosis is needed.The use yeast candida albican is checked the standard activity at fungi.Yet Mycotoruloides comprises many species, the test Candida albicans be because its can be frequent cause candidiasis.Candida albicans can find in digestive tract, oral cavity and vagina, and can cause disease, comprises thrush (also being called thrush), vaginitis, gastrointestinal candidiasis and skin and systemic candidiasis.Especially, the present invention for example controls Candida albicans being effectively aspect the control saccharomycete, contacts after 15 seconds with this antimicrobial compositions, has shown at least 4 logarithm minimizing.

Embodiment 12

[00243] the hand sanitizer composition below the preparation:

A, F=hand sanitizer tester

B, G=contain the hand sanitizer of 2% Cosmowax BP

C, H=contain the hand sanitizer of 3.5% Cosmowax BP

D, I=contain the hand sanitizer of 5% Cosmowax BP

E, J=contain the hand sanitizer of 10% Cosmowax BP

List the prescription of hand below in the table with sanitizer A-J:

Component (% weight)	A，F	B，G	C，H	D，I	E，J
						Deionized water	37.33	35.35	33.87	32.36	27.33
Ultrez10	0.5	0.5	0.52	0.50	0.50
						Cosmowax BP	-	2.02	3.50	5.0	10.0
Ethanol	62.02	62.04	62.0	62.0	62.0
						AMP-95	0.14	0.09	0.11	0.12	0.17
Add up to	100.0	100.0	100.0	100.0	100.0
Initial pH value	3.82	4.10	4.60	4.21	4.05
						The pH value of regulating *	6.19	6.30	6.56	6.31	6.10

^*Regulate the pH value according to test

[00244] the % moisture capacity is provided among Fig. 2 the figure of time of contact.Can find out, add cetearyl alcohol pure and mild ceteareth-20 blend, i.e. sample B-E and G-J can significantly improve the moisture capacity of composition, and this can stop the evaporation of alcohol again.Following table has shown that the high % for the composition of using of the composition that contains Cosmowax BP keeps, particularly in individual hour of the forth day of a lunar month application to skin after.

Embodiment 13

[00245] antiviral composition below the preparation:

A, B=contain the hand sanitizer of 2% Cosmowax BP

C, D=contain the antiviral lotion of 1% cetanol

E, F=contain antiviral lotion 5./.5 of 2% Cosmowax BP

G, H=contain the antiviral lotion .5/.5 of 2% Prolipid 141

I, J=contain the antiviral lotion 1/.5 of 1% cetanol.

Below the table in list hand with sanitizer prescription:

Component (% weight)	A，B	C，D	E，F	G，H	I，J
						Deionized water	35.35	19.9	26.5	26.3	26.5
Ethanol	62.04	70.0	62.0	62.0	62.0
						Ultrez10	0.5		0.5	0.5	1.0
Ultrez20		1.0
						Hydroxyethylcellulose			0.5	0.5	0.5
Isopropyl palmitate		1.0	1.0		1.0
						Glycerine			1.0		1.0
Crodamol CAP			1.0	1.0
						Mineral oil		1.0		1.0
Dimeticone		1.0	1.0	1.0	1.0
						Cosmowax BP	2.02		2.0
Cetanol		1.0			1.0
						Prolipid141				2.0
Malic acid		2.0	2.0	2.0	2.0
						Citric acid		2.0	2.0	2.0	2.0
APM-95	0.09		0.28
						TEA，99％		0.1
Sodium hydroxide				1.2	.82
						Add up to	100.0	100.0	100.0	100.0	100.00
						The pH value of regulating	6.19	3.12	3.51	3.51	3.48

[00246] the % moisture capacity is provided among Fig. 3 the figure of time of contact.Can find out, contain the composition of Cosmowax BP, promptly A, B, E and F after using, As time goes on have bigger moisture capacity, especially the forth day of a lunar month hour, can use following digital proof:

Embodiment 14

[00247] goes back the viral ability of advance copy inventive compositions control.

Sample	A	B	C	D
					Component (% weight)
Deionized water	93.83	37.68	27.53	87.84
					Ethanol		62.05	62.04
Ultrez 10		1.0
					Hydroxyethylcellulose			1.24	1.27
Isopropyl palmitate	1.05	1.0	1.01	1.01
					Glycerine
Dipropylene glycol
					Mineral oil	1.02	1.03	1.0	1.02
Dimeticone	1.08	1.04	1.02	1.03
					Cosmowax BP	3.02	2.01	2.01	2.0
Malic acid		2.0	2.0	2.0
					Citric acid		2.0	2.0	2.0
APM-95		0.18	0.12	1.83
					Add up to	100.0	100.0	100.0	100.0
					The pH value of regulating	3.83	3.51	3.51	3.62
The virus test
					The positive % of hand	100	38	3	0

[00248] preparation above-mentioned composition, test in containing organic acid prescription the Cosmowax BP in (sample B-D) to the effect of skin pH value and antivirus action.Also test does not contain the A control formula (sample A) of organic acid or alcohol.

Sample	The pH value of solution value	Initial skin pH value	2 hours skin pH value	4 hours skin pH value	Virus reduces
						A	3.83	5.26	5.14	N/A	<1 log 10
B	3.51	2.81	N/A	4.20	>2.7 log 10
						C	3.51	3.16	N/A	3.99	>3 log 10
D	3.60	3.64	N/A	4.02	>3 log 10

[00249] the cleaning finger pad of usefulness sample A-D Processing Test object.Composition after the drying, is measured skin pH value immediately on finger pad, for sample A, measured once more afterwards in 2 hours, for sample B-D, measures once more afterwards in 4 hours.With after the compositions-treated 2 hours or 4 hours, with rhinovirus 39 with 3 * 10 ³The titre of pfu is applied on the finger pad.With virus on finger pad dry 10 minutes, wash finger pad with containing the antibiotic viral withdrawal liquid medium of 75% EBSS (Earle ' s balanced salt solution) and 25%FBS (fetal bovine serum) and 1X then.With sample serial dilution in viral withdrawal liquid medium, and be coated on the H1-HeLa cell according to plaque method mensuration titre.

After [00250] four hour, contain the organic acid composition and can cause about 4 skin pH value reading.On the contrary, placebo Composition can not make skin pH value be lower than 5.Composition B can cause the logarithm greater than 2.7 of rhinovirus 39 to reduce, and can make rhinovirus 39 complete deactivations with composition C-D, and it causes the logarithm greater than 3 to reduce.

[00251] antimicrobial compositions of the present invention various product forms be can be mixed with, liquid, gel, semisolid and solid comprised.The fluid product form can be solution, dispersion, emulsion or similar products like form.Gel and soft solid product form can be transparent or opaque, for example, and for utilizing the sticky assignment device or utilizing finger to design.This antimicrobial compositions can be prepared as the composition of diluted for use, or be prepared as the concentrate of dilution before using.

[00252] a kind of specific product form is the fluid composition that is configured in the water soluble package.Packing is joined in the water of right quantity, when the packing dissolving, discharge composition.Water miscible packing typically comprises polyvinyl alcohol.A kind of form of water soluble package is disclosed in U.S. Pat 5,316, and in 688, this paper is introduced into as a reference.Many other water soluble packages are to those skilled in the art, for example, and U.S. Pat 5,070,126; 6,608,121; With 6,787,512; United States Patent (USP) publication 2002/0182348; WO 01/79417; With European patent 0 444 230,1 158 016,1 180 536 and 1 251 147, this paper is incorporated herein by reference each.Capsule is another kind of relevant and useful product form.

[00253] another product form is that antimicrobial compositions is incorporated in absorbent or the adsorbing agent carrier, for example polymer particle or inorganic particle.The load carrier can use by ortho states, or is incorporated in the other products form liquid, gel, semisolid or solid.

[00254] another kind of product form is the fabric that contains compound or composition or the swab that can reduce surface p H value.Then can be by coming to dermal administration compound or composition with the fabric wipe surfaces that contains compound or composition.

[00255] another kind of product form is the article that contain reactive compound or composition, latex glove for example, and described reactive compound or composition are applied to or embed in the article.Use the medicine of compound or composition give antiviral activity can for the surface of article itself and/or article contact.Other article that reactive compound or composition are embedded wherein are plastic cup, packaging material for food and plastic containers.

[00256] just as discussed above, life and inanimate surfaces can be handled according to the inventive method.The surface that is even more important is a mammal skin, application on human skin particularly, thus make bacterium and virally inactivated and block its propagation.Yet this method also can be effective to handle all types of other life surface and inanimate surfaces.

[00257] said composition can be applied to life or inanimate surfaces with some modes, comprise composition spraying, atomizing, spreading and foamed to the surface, or dipping is surperficial in composition.Using of composition can combine for example air spraying, friction or brushing with physical agitation.Using of composition can be manual application, or composition can be used in spray booth.Spray can comprise vaporific material, and its form with the mist particle dispersion under the continuous atmospheric pressure discharges from sprayer unit.

[00258] can also be in the container that contains composition with surface impregnation.The preferred composition that stirs kills the speed that is attached to surperficial microorganism with effect and the solution that improves this solution.

[00259] in another embodiment of the invention, can use the form of foam treatment surface of composition.When in use, can prepare foam by lathering surfactant is mixed with composition.In itself, foaming surfactant can be nonionic, anion or cationic.

[00260] in another embodiment of the invention, can be with thickening or gel combination treatment surface.Under thickening or gel state, composition can keep contacting of long period with the surface, improves anti-microbial effect thus.Thickening or gel combination also can adhere to vertical surface.

[00261] this method also can be used for handling inanimate surfaces, comprises softness and crust.Term used herein " firmly " is meant the surface that comprises the infusibility material, for example glaze watt and no glaze watt, and brick, porcelain, pottery, metal, glass, or the like, and comprise timber and duroplasts, bakelite for example, polystyrene, vinyl, acrylic resin, polyester, or the like.Stiff dough can be porous or imporous.The method of sterilization stiff dough is described in greater detail in U.S. Pat 5,200, and in 189,5,314,687 and 5,718,910, this paper openly is incorporated herein by reference each.

[00262] this method can be used for handling the stiff dough in following: processing factory (for example dairy, wine brewing and food processing factory), health institution (for example hospital, clinic, Surgicenter, dental clinic and laboratory), long-term care mechanism (for example sanatorium), the farm, pleasure-boat, the hotel, aircraft, school and private residence.

[00263] this method can be used for the processing environment surface, for example floor, wall, ceiling and floss hole.This method can be used for treatment facility, for example food processing equipment, dairy equipment, brewery's equipment, or the like.Said composition can be used for handling various surfaces, is included in the food contact surface in food, dairy and the wine brewing factory, for example table top, furniture, tank or the like.This method further can be used for handling implement and instrument, for example medical tool and instrument, and dental tool and instrument, and the equipment that is used for healthcare industry and public kitchen, for example, and cutter, fork, spoon, vessel (for example jar, dish and dish), cutting equipment, or the like.

[00264] treatable inanimate surfaces is including, but not limited to the surface of contact environment, for example table, floor, wall, kitchen utensils (comprising jar, dish, cutter, fork, spoon, plate), food cooking and making surface, comprise dish and food preparation machine, storage tank, drum, pipeline, pump, flexible pipe, and other process equipment.

[00265] a kind of effective application of composition is the dairy equipment that contact is made of glass or stainless steel usually.Dairy equipment be can find at dairy installation with in the Dairy Processing device, processed milk, cheese, ice cream and other dairy products are used for.Another kind of effectively the application is in the bird facility, comprises poultry farms, poltry factory and has other facility of raw material poultry contact surface, for example supermarket, butcher's and restaurant.

[00266] in use, composition can be applied to target life and inanimate surfaces.Can followingly use composition: with surface impregnation in composition, in composition, soak the surface, or with composition spray, wiping, foamed, mistization (misting), brushing, liner is coated with stain, spreading, smears, uses sponge wiping or atomizing (fogging) on life or inanimate surfaces.Can manually use composition, or use equipment, for example spray bottle, or utilization machinery, for example sprayer, frothing machine or the like.Can also be at the machinery inner composition that uses of ware wash machine or washing machine for example.For domestic. applications, can use manual pump type or pressure atomization device.Can also use composition to be coated with stain or handle material for example sponge, fiber or non-fabric, swab, flexible plastic, textile, timber or the like.Usually, use coating processes, by being coated with the described surface of stain with composition to prolong porous or the antiviral performance of pore-free surface.

[00267] method of the present invention can also be used to make beverage and comprise fruit juice, malt beverage, bottled water product, tea and soft drink.This method can be used for handling pump, pipeline, storage tank and mixing apparatus of using or the like in making such beverage.Method of the present invention also can be used for handling air cleaner.

[00268] method of the present invention can be effective to handle medical operating go-cart, medical shrouding, and other Medical Instruments, device and equipment.Example with the treatable Medical Devices of this method is disclosed in United States Patent (USP) U.S.6, in 632,291, is incorporated herein by reference.This method also can be effective to handle utensil and the chair that is present in barber shop and hair and the nail salon institute.Further useful applications is to handle coin, bank note, cost board, playing card chip and those to be many people's repeated touches and can be at the similar article of interpersonal transmitted virus.

[00269] except stiff dough, this method also can be used for handling soft inanimate surfaces, textile for example, and clothes for example, vest, laboratory clothing, operation dress, johnny, blanket, bedding, towel, lingerie, or the like.This method also can be used for handling the associated garments of face shield, medical gown, gloves and doctor and dentist's use.

[00270] antimicrobial compositions of the present invention has the purposes of some practicality, comprises cleanser/hand, operation abrasive cleaner, body sprays, preservative, disinfectant, hand disinfecting gel, deodorant and similar personal care product.The composition of other type comprises emulsifiable paste, ointment or the like, and contains organic and composition inorganic filler material, for example emulsion, lotion, paste or the like.Composition further can for example, be used for the tank and the table top of hospital, catering service zone, school, pleasure-boat and meat and poltry factory as the antimicrobial of inanimate surfaces.This antimicrobial compositions can be prepared into the composition of diluted for use, or be prepared into the concentrate of dilution before using.

[00271] just as discussed above, life and inanimate surfaces can be handled according to the inventive method.The surface of particular importance is a mammal skin, people's skin particularly, thus make bacterium and virally inactivated and block its propagation.Yet this method also can be effective to handle all types of inanimate surfaces.

Therefore [00272] present invention resides in the antimicrobial cleansing compositions of the present invention of using effective dose on the non-skin surface, family surface for example, for example, table top, the surface, kitchen, the food preparation surface (chopping block, dish, jar and plate, or the like); Main household electrical appliance, for example, refrigerator, refrigerator, washing machine, automatic dryer, baking oven, micro-wave oven, and dish-washing machine; Cupboard; Wall; The floor; Bathroom surfaces, shower, dustbin, and/or recycle dustbin, or the like.

[00273] in an embodiment of the present invention, (a) suffer from the rhinovirus flu and maybe may contact other individual personnel that suffer from the rhinovirus flu, or (b) suffer from rotavirus infection and maybe may contact other individual personnel that suffer from rotavirus infection, use antimicrobial compositions of the present invention can for his or his hand.This is used can killing bacteria and make rhinovirus, rotavirus and other nonenveloped virus particle inactivation that is present on hand.The composition of using is remained on hand and lasting antiviral activity is provided.Therefore, for example rhinovirus or rotavirus virion can not propagated the individuality that infects to not by hand adversary circulation way to nonenveloped virus.The amount that composition is used, frequency of administration and operating period will change according to needed sterilisation level, for example the degree of microbial contamination and/or skin contamination.

[00274] in short time of contact, antimicrobial compositions of the present invention can provide wide spectrum to kill the benefit of Gram-positive and Gram-negative bacteria and the control of wide spectrum virus.In short contacting time, cause bacterium in fact logarithm to reduce be important, this is because the time range of be used to sterilize skin and inanimate surfaces 15 to 60 seconds typically.Said composition is returned contact surface and has been given lasting antiviral activity.

[00275] in short contacting time, composition of the present invention is effective, this is because the pH value of the reduction of composition and the synergistic effect that the pure and mild organic acid coupling of sterilizing is provided, and lasting activity obtains increasing, and this is owing to can keep the residual barrier layer or the film of composition component on skin after the volatile component evaporation of composition.This composition also provides owing to there being C ₁₂To C ₂₂The anti-bacterial effect of the prolongation of alcohol, C ₁₂To C ₂₂The existence of alcohol has stoped the evaporation of alcohol in the composition.In addition, this composition has proved because of the moisture capacity of handled skin height and has reduced skin irritation.

[00276] obvious, under the conditions without departing from the spirit and scope of the present invention, can carry out many improvement and variation to the present invention listed above, therefore, only should apply as this restriction as indicated in the additional claim.

Claims (68)

1. method that reduces bacterium and virus population from the teeth outwards, comprise making the surface and can after contact 30 seconds, obtaining to contact with composition that described composition comprises at the logarithm minimizings of Escherichia coli at least 2.5 at the minimizing of the logarithm of staphylococcus aureus at least 2:

(a) about 25% sterilization alcohol to about 75% weight;

(b) about 0.1% the C that contains to about 20% weight ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂The blend of alcohol;

(c) organic acid of the optional effective dose of killing the virus; With

(d) water.

2. the process of claim 1 wherein that composition contains organic acid, and have about 5 or littler pH value at 25 ℃.

3. the method for claim 2 wherein contacted after 30 seconds, and composition can obtain to reduce at the logarithm of nonenveloped virus at least 4.

4. the method for claim 3, wherein virus is sour unsettled virus.

5. the method for claim 3, wherein sour unsettled virus comprises rhinovirus serotype.

6. the method for claim 3, wherein virus comprises rotavirus serotype.

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

8. the method for claim 2, wherein composition is reduced to less than 4 the pH value of mammalian skin after dry on skin.

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

10. the process of claim 1 wherein and composition is kept from the teeth outwards and drying.

11. the method for claim 2, wherein the surface has lasting antiviral activity.

12. the method for claim 2, wherein composition forms from the teeth outwards and comprises the organic acid barrier layer.

13. the method for claim 2, wherein formation comprises the layer that organic acid is continuous basically from the teeth outwards.

14. the method for claim 2, wherein water washes after three times, and the non-volatile component of at least 50% weight of composition is present on the surface.

15. the process of claim 1 wherein that the surface has the antibacterial activity of prolongation.

16. the process of claim 1 wherein that sterilization alcohol comprises one or more C _1-6Alcohol.

17. the process of claim 1 wherein that sterilization alcohol is selected from: methyl alcohol, ethanol, isopropyl alcohol, n-butanol, normal propyl alcohol and its mixture.

18. the process of claim 1 wherein that blend comprises cetearyl alcohol pure and mild ceteareth-20 blend; Cetostearyl alcohol, stearyl alcohol polyethers-20 and stearate-10 blend; Or its mixture.

19. the method for claim 2, wherein composition comprises about 0.1% organic acid to about 15% weight.

20. the method for claim 2, wherein the organic acid in the composition has the log P less than.

21. the method for claim 2, wherein the organic acid in the composition has one or bigger logP.

22. the method for claim 2, wherein organic acid comprises having less than first organic acid of one log P and have one or second organic acid of bigger log P.

23. the method for claim 2, wherein organic acid comprises one or more monocarboxylic acid, and polybasic carboxylic acid has multiple carboxylic acid, phosphate, sulphonic acid ester and/or sulfuric ester polymeric acid partly, its acid anhydrides, or its mixture.

24. the method for claim 2, wherein organic acid comprises and has structure RCO ₂The monocarboxylic acid of H, wherein R is C _1-6Alkyl, hydroxyl C _1-6Alkyl, halo C _1-6The phenyl of alkyl, phenyl or replacement.

25. the method for claim 24, wherein monocarboxylic acid is selected from: acetate, propionic acid, glycolic acid, lactic acid, benzoic acid, phenylacetic acid, phenoxyacetic acid, zimanic acid, 2-, 3-or 4-hydroxybenzoic acid, aminobenzenesulfonic acid, adjacent, or rubigan acetate, adjacent, or parachlorophen-oxyacetic acid and its mixture.

26. the method for claim 2, wherein organic acid comprises and contains two to four carboxylic acid groups' polybasic carboxylic acid with optionally comprise one or more hydroxyls, amino or both.

27. the method for claim 26, wherein polybasic carboxylic 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 its mixture.

28. the method for claim 26, wherein organic acid comprises the acid anhydrides of polybasic carboxylic acid.

29. the method for claim 2, wherein organic acid comprises having about 500 to about 10,000, the polymeric acid of 000g/mol molecular weight.

30. the method for claim 29, wherein polymeric acid be water-soluble or water dispersible.

31. the method for claim 29, wherein polymeric acid is selected from polymerization of carboxylic acid, polymerization sulfonic acid, sulfated polymers, polymer phosphate and its mixture.

32. the method for claim 29, wherein polymeric acid comprises acrylic acid homopolymers or copolymer.

33. the method for claim 2, wherein organic acid comprises polybasic carboxylic acid and polymerization of carboxylic acid.

34. the method for claim 33, wherein polybasic carboxylic acid comprises citric acid, malic acid, tartaric acid and its mixture, and polymerization of carboxylic acid comprises the homopolymers or the copolymer of acrylic or methacrylic acid.

35. the method for claim 34, wherein polymerization of carboxylic acid comprises acrylic acid homopolymers or copolymer.

36. the method for claim 33, wherein composition further comprises gelling agent.

37. the method for claim 2, wherein composition has about 2 to less than about 5 pH value.

38. the method for claim 8, wherein contact is four hours afterwards, and mammalian skin has the skin pH value less than 4.

39. the process of claim 1 wherein that composition further comprises about 0.1% gelling agent to about 3% weight.

40. the method for claim 39, wherein gelling agent comprises natural gum, synthetic polymer, clay, oil, paraffin or its mixture.

41. the method for claim 39, wherein gelling agent is selected from cellulose, cellulose derivatives, guar gum, guar gum derivatives, algin, algin derivative, water-fast C ₈-C ₂₀Alcohol, carrageenan, smectic clays, polyquaternium compound and its mixture.

42. the process of claim 1 wherein that composition does not contain anion, cation and amphoteric surfactant.

43. the process of claim 1 wherein that composition further comprises active antibacterial agent.

44. the method for claim 43, wherein active antimicrobial agent comprises and is selected from following phenols antimicrobial:

(a) has the 2-hydroxydiphenyl compounds of following array 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, and m is 0 or 1, and n is 0 or 1;

(b) have the amphyl of following array structure:

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 ₆The sulphur of alkyl, hydroxyl, chlorine, nitro or alkali metal salts or ammonium salt form, R ₄Be hydrogen or methyl, R ₅Be hydrogen or nitro;

(c) have the diphenyl compounds of following array structure:

Wherein X is sulphur or methylene, R ₆And R ' ₆Be hydroxyl, R ₇, R ' ₇, R ₈, R ' ₈, R ₉, R ' ₉, R ₁₀And R ' ₁₀Be hydrogen or halogen independently of one another; With

(d) its mixture.

45. the method for claim 43, wherein antimicrobial comprises triclosan, between chloro--xylenols, hydrogen peroxide, benzoyl peroxide, phenmethylol, quaternary ammonium compound, or its mixture.

46. the method for claim 12, wherein water washes after ten times, and the organic acid of the effective dose of killing the virus is retained in the lip-deep barrier layer.

47. the method for claim 2, the wherein fungi on the further control surface of composition.

48. the method for claim 47, wherein fungi comprises mould, saccharomycete or both.

49. the method for claim 48, wherein fungi comprises saccharomycete.

50. the method for claim 49, wherein saccharomycete comprises Candida albicans.

51. the method for claim 47 wherein contacts composition after 15 seconds, composition is given at least 4 logarithm minimizing at lip-deep Candida albicans.

52. one kind makes virally inactivated and method kill bacteria, comprises life or the inanimate surfaces topical composition handled like this to needs,

Described composition comprises;

(a) about 25% sterilization alcohol to about 75% weight;

(b) about 0.1% the C that contains to about 20% weight ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂The blend of alcohol;

(c) the kill the virus organic acid of effective dose; With

(d) water.

53. the method for claim 52 is wherein given the lasting antiviral effect in surface and the antibacterial effect of prolongation.

54. the method for claim 52 wherein can make virally inactivated up to about 8 hours.

55. the method for claim 52 wherein makes composition keep from the teeth outwards and drying.

56. the method for claim 52 wherein makes the nonenveloped virus inactivation.

57. the method for claim 52 wherein makes rhinovirus, picornavirus, adenovirus, rotavirus, herpes virus, Respiratory Syncytial Virus(RSV), coronavirus, enterovirus, rotoviruses and similar pathogenic virus inactivation.

58. the method for claim 52 wherein makes acid unsettled virally inactivated.

59. the method for claim 52 wherein makes the rhinovirus inactivation.

60. a method of protecting individual rhinovirus and rotavirus infection comprises to the skin of individuality and uses composition with the amount of enough eliminating rhinovirus and rotavirus,

Described composition comprises:

(a) about 25% sterilization alcohol to about 75% weight;

(b) about 0.1% the C that contains to about 20% weight ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂The blend of alcohol;

(c) the kill the virus optional organic acid of effective dose; With

(d) water.

61. the method for claim 60 was wherein used composition before individuality is exposed to rhinovirus or rotavirus.

62. the method for claim 60 is wherein repeatedly used composition within twenty four hours.

63. the method for claim 60 wherein makes composition be retained on the skin.

64. an antimicrobial compositions comprises:

(a) about 25% sterilization alcohol to about 75% weight;

(b) about 0.1% the C that contains to about 20% weight ₁₂To C ₂₂Pure and mild ethoxylation C ₁₂To C ₂₂The blend of alcohol;

(c) about 0.1% organic acid to about 15% weight; With

(d) water.

65. the composition of claim 64 further comprises about 0.01% gelling agent to about 5% weight.

66. the method for claim 64, wherein composition has about 2 to less than about 5 pH value.

67. the composition of claim 64, wherein organic acid comprises polybasic carboxylic acid and has a plurality of carboxylic acid groups' polymeric acid.

68. the composition of claim 67, wherein polybasic carboxylic acid comprises malic acid, citric acid, tartaric acid and its mixture, and polymeric acid comprises the homopolymers or the copolymer of acrylic or methacrylic acid.

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