CN101460053A - Methods and articles having a high antiviral and antibacterial efficacy - Google Patents

Abstract

Method and article for providing a rapid, broad spectrum bacterial control, and a rapid and persistent antiviral control on an inanimate surface is disclosed. In the method, a compound or composition capable of lowering surface pH to less than about 4 is applied to the surface, and preferably is allowed to remain on the surface, and the nonvolatile components of the composition can form a barrier film or layer on a treated surface.

Description

Method and article with high antiviral and antibacterial effect

The cross reference of related application

[0001] the application requires the U.S. Provisional Patent Application US60/811 of application on June 5th, 2006, the U.S. Provisional Patent Application US60/811 of 032 rights and interests and application on June 6th, 2006,354 rights and interests.

Invention field

[0002] the present invention relates in the method that the virus control that provides quick and lasting on life or the inanimate surfaces is arranged and fast, the method for the control bacterium of wide spectrum, especially on food contacting surface.More particularly, the present invention relates to control from the teeth outwards the method for virus and bacterium, this method is administered to compound or composition on the surface, can provide less than about 4 surface p H value about four or more hours, and the surface is not had excitant or corrosivity.This compound is (a) organic acid typically, (b) inorganic acid, and (c) mineral salt, (d) complex compound of aluminium, zirconium or aluminum-zirconium or (e) its mixture can reduce surface p H value fully, thus control virus and bacterium.Randomly, described surface can with sterilization alcohol and antibacterial agent in a kind of or both contact, thereby bacterium and virus are controlled in help.In some embodiments, compound and composition can provide barrier layer or film on handled surface, thereby give the surface with lasting antiviral activity.This method can be controlled Gram-positive and gram-negative bacteria population and virus population within one minute, and the permanent disease-resistant poison control of about four hours or more hours is provided.The invention still further relates to the article of inclusion compound or composition, and relate to the method for using compound or compositions-treated inanimate surfaces.

Background of invention

[0003] health is subjected to run into every day the influence of various microorganisms.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 in first road defence of removing from these surfaces this pathogene 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 in the main pathogens that receives publicity one type.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, among all mammals comprised people, pet, domestic animal and zoo animal, virus infected each organism in fact, and simultaneously, virus infections generation speed 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 surrounds the simple protein housing.Roughly 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 propagated 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, and in order to infiltrate cell, virus at first must be attached to cell surface.Virus is that for most of selectivity of some cell type it has the ability that is attached to the specific cells surface.For 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 allow its complete 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 crust 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.Rhinovirus is the member of picornavirus family, and it is the family that lacks " nonenveloped 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.102 kinds of rhinovirus serotypes are formally arranged.The most of picornavirus acid labile that from the human respiratory system, separates, 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 form that directly contacts with contaminated surface, rather than via sucking airborne virion.

[0011] after initial the pollution, rhinovirus can survive on environmental surfaces many hours.When wiping one's eyes with the finger that just pollutes or contacting schneiderian membrane, rhinovirus infection contacts with finger with contacting with finger by the contaminated environment surface by finger easily and propagates.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, 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 and not between the immune body hand in hand, the direct contact of hand lip-syncing or droplet transfer mode propagates, or when the individuality that does not infect contacts the solid objects of hepatitis A virus pollution, pass through indirect contact transmission.Many other virus infectionses are also propagated in a similar fashion.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, make its at virus for example rhinovirus have lasting activity.

[0014] antibiotic personal care composition is well known in the art.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] bactericidal composition 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 will control that bacterial population places critical role on the 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.

The antibiotic personal care composition of [0016] one class is the hand sanitizer.This based composition mainly is used for to hand and finger sterilization by the medical worker.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 gel, and alcohol itself serves as disinfectant.In addition, pure rapid evaporation can be avoided wiping or the flushing skin with the disinfecting Gel Treatment.Contain at high proportion alcohol (be composition weight about 40% or bigger) hand can not provide lasting bacteria inactivation with sanitizer.

[0018] antibiotic Cleasing compositions typically contains antimicrobial activity, surfactant and various other component in moisture and/or alcohol carrier, for example dyestuff, spices, pH value conditioning agent, skin conditioning agent or the like.Some different classes of antibacterial agents have been used to antibiotic Cleasing compositions.The example of antibacterial agent comprises the phenol and the phenolic compound of two guanidines (for example Chlorhexidine digluconate), diphenyl compounds, phenmethylol, three halogenated diphenyl ureas, quaternary ammonium compound, ethoxylation, 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 bactericidal composition of this antibacterial agent, this depends on the microorganism controlled and concrete bactericidal composition.

[0019] most of commercial bactericidal composition provides usually and is low to moderate medium antibacterial activity, and does not report antiviral activity.Evaluation comprises Gram-positive and Gram-negative microorganism at the antibacterial activity of broad-spectrum micro-organisms.The logarithm minimizing value of the bacterial population that bactericidal composition provides or minimizing percentage are relevant with antibacterial activity.From the concrete time of contact in 15 seconds to 5 minute, the logarithm minimizing value of 1-3 is preferred for usually, and the logarithm minimizing value of 3-5 is most preferred, and is least preferred less than 1 logarithm minimizing value.Thus, highly preferred bactericidal composition has demonstrated the logarithm minimizing value of 3-5 to broad-spectrum micro-organisms in short time of contact.

[0020] yet, virus control is more difficult problem.By abundant reduction bacterial population, risk of bacterial infections can be reduced to acceptable degree.Therefore, antibiotic fast deactivation is a target.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.Ideally, single virus can cause infection.Therefore, for effective antiviral Cleasing compositions, need or need at least complete and lasting in fact antiviral activity.

[0021] WO 98/01110 discloses the composition that comprises triclosan, surfactant, solvent, chelating agent, thickener, buffer and water.WO 98/01110 points to and uses the surfactant of low quantity to reduce 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 anionic surfactant and nonionic surface active agent.

[0023] EP 0 505 935 discloses the composition that combines that contains PCMX and nonionic and anionic surfactant (the especially block copolymer surfactant of nonionic).

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

[0025] WO 95/09605 discloses the bactericidal composition that contains anionic surfactant and alkyl poly glucoside surfactant.

[0026] WO 98/55096 discloses the cleaning piece with porous sheet, porous sheet is flooded with bactericidal composition, described bactericidal composition contains antimicrobial activity, anionic surfactant, acid and water, and wherein composition has about 3.0 to about 6.0 pH value.

[0027] U.S. Pat 6,110, and 908 disclose a kind of topical germicide, and it contains C _2-3Alcohol, free fatty acid and oxygen mercaptopyridine zinc.

[0028] 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 the combination of antimicrobial activity and surfactant.

[0029] 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.

[0030] use the disinfecting gel while you're at it and opinion, U.S. Pat 5,776,430 disclose a kind of local antibacterial 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 hand disinfectant, and its pure and mild gross weight that contains antibacterial agent, 40% to 90% weight is no more than the polymer and the thickener of 3% weight.The gel friction is entered in the hand, and evaporation, to sterilize to hand.The composition of the disclosure usually can not provide sanitized immediately, and lasting antibacterial effect can not be provided.As 0 604848 of EP are illustrational, do not think that the quantity of antibacterial agent and characteristic are important, because hand comprises a high proportion of alcohol with the disinfecting gel, thereby provide antibacterial activity.

[0032] common, hand typically contains with the disinfecting gel: (a) for example combination 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, wipes hand disinfecting gel on watch face.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 using, main active disinfectant can not be retained on the skin, can not provide lasting antibacterial action 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, typically there is extra antimicrobial compound, so that antibacterial activity to be provided.Yet, the previous open problem that is not illustrated in the component of the composition that control of microorganisms can be provided in such bactericidal composition.Therefore, for the preparation that contains low determining alcohol, be difficult for the selection that not only can provide the quick antibacterial result but also have an antibacterial agent of durable antibiotic benefit.

[0034] U.S. Pat 6,107, and 261 and 6,136,771 disclose bactericidal composition efficiently.These patent disclosures solve the composition of problem of bacteria on control skin and the crust, but how record does not control virus.

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

[0036] composition that discloses the anionic surfactant that comprises quaternary ammonium compound and selection is effectively (for example U.S. Pat 5,798,329) in some applications, is not used for personal care composition but speak of this combination.

[0037] discloses the patent of the bactericidal composition that comprises the quaternary ammonium antibacterial agent and comprised U.S. Pat 5,798,329 and 5,929,016 with openly applying for; WO97/15647; And EP0651048, relate to antimicrobial laundry washing agent and antibiotic hard surface cleaner.

[0038] it is also known that, make the pathogenic virus inactivation or, comprise rhinovirus, rotavirus, influenza virus, parainfluenza virus, Respiratory Syncytial Virus(RSV) and Norwalk virus the antiviral composition that it is eliminated.For example, U.S. Pat 4,767,788 disclose and use glutaric acid to make to comprise the virally inactivated of rhinovirus or it is killed.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 provides medicament and surfactant (comprising the antimicrobial surface activating agent) to realize antiviral and anti-microbial property.

[0039] 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 combination of salicylic acid and selected slaine can effectively resist virus, comprise rhinovirus.U.S. Pat 6,436,885 disclose the combination of antibacterial agent and 2-Pyrrolidone-5-carboxylic acid known under 2 to 5.5 pH value condition, so that antibiotic and antiviral performance to be provided.

[0040] organic acid in personal wash compositions is also disclosed.For example, WO 97/46218 and WO 96/06152 disclose and used organic acid or salt, hydrotropic agent, triclosan and hydroxyl solvent in the surfactant base-materials of antibiotic cleaning composition.These publications are not put down in writing antiviral performance.

[0041] people's such as Hayden Antibacterial Agents 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.

[0042] 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, 752:493-497 (1985)) report, hand adversary that can blocking virus with kill the 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 mixes in the fabric that kills the virus.

[0043] U.S. Pat 4,503, and 070 discloses the method for treatment common cold, and this method is given oral mucosa local application zinc gluconate.By alleviating common cold symptoms, this method has reduced the duration of flu.U.S. Pat 5,409,905 also disclose the method for treatment common cold, and this method uses the solid composite that comprises zinc ion for people's oral cavity and oropharyngeal membrane.U.S. Pat discloses the method for treatment common cold, comprises that patient's nasal openings and the respiratory tract to needs gives spray, and spray comprises basically the not solution of the zinc ion compound of chelating.U.S. Pat 6,673,835 disclose a kind of method and composition, by being applied to nasal cavity, are used for providing low but the effective active component that comprises zinc of quantity to blood.

[0044] be difficult to the effective ways that bacterium and virus population are controlled in acquisition, this is owing to have basic difference between bacterium and virus population.The method that provides lasting antiviral activity that is difficult to more obtain.Though there are many antibiotic cleaning products at present, product form different (for example deodorant soap, hard surface cleaner and operation disinfectant), but this antimicrobial product has typically been introduced high-caliber alcohol and/or surfactant, and it can make the skin tissue dry and uncomfortable.Ideally, individual bactericidal composition and method be cleaning skin leniently, does not almost have excitant, and can not make skin over-drying after frequent the use.

[0045] correspondingly, method existence needs for the broad-spectrum micro-organisms (comprising virus and Gram-positive and Gram-negative bacteria) on the efficient control surface (particularly food contacting surface) at short notice, wherein this method provides lasting antiviral activity, and is gentle to the surface.Obtained the reduction virus of improvement and the method for bacterial population are provided by the present invention, comprised the method for the lasting reduction that virus population is provided.

The present invention's general introduction

[0046] the present invention relates on surface the crust of storage and sale of foodstuffs (especially process, make), to provide the method and the article of antiviral fast and antibiotic control and lasting antiviral control.This method can provide substantial virus control and reduce Gram-positive and Gram-negative bacteria significantly within less than about one minute.

[0047] more particularly, the invention provides the method for killing broad spectrum of bacteria, this bacterium comprises Gram-positive and Gram-negative bacteria, for example aurococcus, hog cholera Salmonella, Escherichia coli and Klebsiella, can make simultaneously to harmful virally inactivated of health or with its elimination, described virus especially sour unsettled virus, particularly rhinovirus and other sour unsettled picornavirus.Can also control influenza virus and norovirus.

[0048] correspondingly, one aspect of the present invention provides virus on the control warm blooded animal skin and the method for bacterium, comprise make hard or soft inanimate surfaces with surface p H value can be reduced to less than about 4, the compound or the composition of surperficial discomfort are contacted.In some embodiments, this method can provide the bacterial control of wide spectrum and lasting virus control to continue to much about eight hours.Said composition has about 5 or littler pH value, and the continuous basically layer or the film of composition component are provided on handled surface, thereby gives lasting antiviral activity for handled surface.In preferred embodiments, described composition further comprises gelling agent.Optional antimicrobial activity also can be contained in the described composition.

[0049] another aspect of the present invention provides bacterium and the viral method on the control surface, comprise to the dermal administration composition, described composition comprises complex compound or its mixture of organic acid, inorganic acid, mineral salt, aluminium, zirconium or aluminum-zirconium, to reduce surface p H value fully, and suppress bacterium and virus thus, and Diazolidinyl Urea not.

[0050] another aspect of the present invention provide the control of the time of lasting prolongation have on life or the inanimate surfaces bacterium and virus method, comprise described surface is contacted with moisture bactericidal composition, said composition comprises and is selected from following compound: (a) organic acid, and it is selected from monocarboxylic acid, polybasic carboxylic acid, has a plurality of carboxyls, the polymeric acid of phosphate radical, sulfonate radical and/or sulfate radical part and composition thereof; (b) to the non-irritating inorganic acid of skin; (c) mineral salt, it comprises and has 2,3 or 4 valent cation and counter ions, (d) complex compound of aluminium, zirconium or aluminum-zirconium and (e) its mixture, wherein composition can be reduced to surface p H value less than about 4.Said composition has less than about 5 or littler pH value, and the residual layer of composition component can be provided on handled surface.

[0051] another aspect of the present invention provides a kind of antibiotic and bactericidal composition antiviral activity of having, it is firm to the surface, and/or can not infiltrate the surface, and/or hold out against surface washing, and/or form continuous basically barrier layer from the teeth outwards, for example hydrophobic monocarboxylic acid, polybasic carboxylic acid, the polymeric acid with many carboxyls, phosphate radical, sulfonate radical and/or sulfate radical part or its mixture and (c) water, wherein composition has about 5 or littler pH value.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 nonenveloped virus.Said composition also can be resisted influenza virus and norovirus effectively.Lasting antiviral activity is partly owing to lip-deep organic acid residual layer or the film of comprising of handle, and it can be after through flushing several times and can not remove from skin, and is keeping several hrs during every day normally.Preferred compositions comprises one or more polybasic carboxylic acids, polymeric acid and gelling agent.These compositions provide the effective and lasting control for nonenveloped virus, and demonstrate the synergistic activity at Gram-positive and Gram-negative bacteria.

[0052] in preferred embodiments, said composition provides the continuous basically layer or the film of non-volatile composition component on handled surface, so that give lasting antiviral activity for handled surface.In other embodiment preferred, said composition does not contain the surfactant that on purpose adds.

[0053] preferred compositions comprises one or more polybasic carboxylic acids, polymeric acid and gelling agent.These compositions provide the effective and lasting control to virus, and demonstrate the synergistic activity at Gram-positive and Gram-negative bacteria.

[0054] another aspect of the present invention provides the product form of sending bactericidal composition, comprises solid, semisolid, gel and product liquid form.

[0055] another aspect of the present invention provides the method for the bacterial control that obtains wide spectrum basically on handled surface and lasting virus control.

[0056] another aspect of the present invention provides a kind of method, and after contact 30 seconds, this method has obtained to be at least 2 logarithm minimizing value at Gram-positive bacteria (being aurococcus).

[0057] another aspect of the present invention provides a kind of method, and after contact 30 seconds, this method has obtained to be at least 2.5 logarithm minimizing value at Gram-negative bacteria (being Escherichia coli).

[0058] another aspect of the present invention provides a kind of method, after contact 30 seconds, it demonstrates at least 4 logarithm minimizing value at the unsettled virus of acid on warm blooded animal, described virus comprises rhinovirus serotype, for example rhinovirus 1a, rhinovirus 14, rhinovirus 2 and rhinovirus 4.After using 30 seconds time of contact, this bactericidal composition also provides the logarithm minimizing value (about 6 hours) of at least 3 logarithm minimizing value (about at least 5 hours) and at least 2 at nonenveloped virus.In some embodiments, this bactericidal composition provides 2 logarithm minimizing value (about at the most eight hours) at nonenveloped virus.

[0059] another aspect of the present invention provides a kind of method, and after compound or composition were applied to the surface, this method obtained lasting antiviral activity, for example continued about four hours or more hours.After compound or composition were applied to inanimate surfaces, this method went up at inanimate surfaces (for example food contacting surface) and obtains lasting antiviral activity.

[0060] another aspect of the present invention provides bactericidal composition, it can be withstood and not fallen from surface washing, 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.

[0061] another aspect of the present invention provides consumer products, for example skin cleaner, body sprays, operation abrasive cleaner, Wound care agent, hand with sanitizer, disinfectant, shampoo for pets, hard or soft-surface sanitizer, lotion, ointment, ointment, solid, emulsifiable paste or the like, its can with the surface for example the pH value of warm blooded animal skin be reduced to less than about 4, thereby realize broad spectrum of bacteria control fast and lasting virus control, not Diazolidinyl Urea.These consumer products can be flushable fall type or conservative products.Preferably, allow product to be retained on the handled surface, thereby allow the pH value reduction component of product to be retained on (preferably substantially being deposited on) surface, to increase lasting antiviral control.Said composition is desirable on the surface on aesthetic, and to surperficial nonirritant, and for example continuous basically residual film or the layer of organic acid of non-volatile composition component is provided from the teeth outwards.

[0062] further aspect of the present invention provides the wide spectrum virus controlled apace in animal tissue's (comprising human tissue) and the method for Gram-positive and/or Gram-negative bacteria population, this method comprises: make and for example organize that corium contacts time enough with compound or composition, for example about 15 seconds to 5 minutes or longer, for example about one hour, so that tissue pH is reduced to less than about 4, thus bacterium and virus population is reduced to needed level.Further aspect of the present invention provides the method that obtains to control enduringly the virus in the animal tissue.

[0063] another aspect of the present invention provides the disease that treatment or pre-anti-virus mediated and the method for illness, and this disease and illness be caused by rhinovirus, rotavirus, picornavirus, adenovirus, herpes virus, Respiratory Syncytial Virus(RSV) (RSV), coronavirus, enterovirus and other nonenveloped virus.This method also can treat and prevent by influenza mediation and by the disease and the illness of norovirus mediation.

[0064] another aspect of the present invention provides the method that blocking virus is propagated to lived surface (especially warm blooded animal skin) from animate and inanimate surface.Especially provide the control nonenveloped virus, especially the method propagated of rhinovirus, by to dermal administration suitable compound or composition, control the virus that exists on application on human skin and the inanimate surfaces effectively, and control about four or more a plurality of hours of virus continuously, and about at the most eight hours.

[0065] 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

[0066] Fig. 1 a and 1b are the reflection microphotos, shown the lip-deep non-volatile component that after giving the surface applied present composition, is provided barrier layer and

[0067] Fig. 1 c and 1d are the reflection microphotos, have shown do not have barrier layer on the surface afterwards for the surface applied reference composition.

Detailed description of preferred embodiments

[0068] personal care product of introducing antimicrobial activity is known many year.Because antibiotic personal care product's introducing provides anti-microbial property to propose many claims to this product.The most effectively, bactericidal composition should provide the logarithm minimizing value at the broad-spectrum biological height in short as far as possible time of contact.Ideally, said composition also should make virally inactivated.

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

[0070] antibiotic hand does not typically contain surfactant with sanitizing compositions, and relies on the alcohol of high concentration to suppress bacterium.The alcohol evaporation, and therefore can not provide lasting control of microorganisms.Alcohol also may make dry skin and discomfort.

[0071] most of existing product especially lacks at Gram-negative bacteria, for example colibacillary effect, and these bacteriums health with human body especially are relevant.Yet, there is composition (quick inactivating (being the time limit deactivation) by bacterium is measured) really with extra high broad-spectrum antimicrobial effect, it is different from lasting deactivation.These products also lack enough antiviral activities.

[0072] compare with the composition that uses a high proportion of alcohol (promptly 40% or bigger weight) with previous method, this method sensing provides the effect of outstanding broad-spectrum antiseptic, and has improved antibiotic effect significantly.The basis of finding this raising effect is for example reduction of warm blooded animal skin (comprising human skin) pH value of surface, provides fast, the bacterial control of wide spectrum and controlling with lasting virus fast.Importance of the present invention is the surface p H 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 from the teeth outwards, and it can provide the bank of the compound that keeps low skin pH value.

[0073] term " continuous basically film " is meant the residue of non-volatile component of the composition of barrier layer form, and at least 50%, at least 60%, at least 70% or at least 80% preferably at least 85% or 90% and more preferably at least 95% is present on the handled surface area regions at least.In the reflection microphoto 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.

[0074] though contain antibacterial agent 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.

[0075] for example, rhinovirus is and the relevant most important microorganism of acute respiratory disease (being 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 ideally.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.

[0076] because rhinovirus is the main known reason of common cold, so importantly, has the composition controlled rhinovirus serotype of antiviral activity.Though understood rhinoviral molecular biology now, the effective ways of infected patient are unsuccessful to find to give prevention caused flu of rhinovirus and prevention virus disseminating not.

[0077] 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 prolong the cycle that the blocking-up rhinovirus infection is propagated effectively.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 local application composition that demonstrates antiviral activity can effectively prevent and/or treat by the caused disease of other sour unsettled virus.

[0078] 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 for example especially is a problem in child care device, seniculture device, family, pregnant woman hospital in airtight community.

[0079] 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.

[0080] knownly washes one's hands and inanimate surfaces 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 there are not other effective ways of eliminating rotavirus or its propagation at present, in airtight community, especially the staff in those communities of children must adhere to strict health practice, with the propagation that helps to subdue rotavirus.Make aspect the rotavirus inactivation, the improvement composition with antiviral effect (comprising lasting antiviral effect) of increase will further be subdued the propagation of rotavirus infection.

[0081] viricidal method can make virally inactivated or it is killed.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 for a long time significant antiviral activity is provided.In some embodiments, " lasting antiviral effect " or " lasting antiviral activity " is meant: after using, on life surface (for example skin) or inanimate surfaces, keep the barrier residue layer or the film of antivirotic, thereby for a long time significant antiviral activity is provided.Barrier residue layer or film can be continuously or continuous basically, and can resist between the water flush period and not by removing from handle surface.

[0082] the inventive method can provide lasting antiviral effect, promptly preferably within 30 seconds, at the unstable virus of pathogenic acid for example rhinovirus serotype have at least 3 logarithm minimizing value, and the more preferably logarithm minimizing value of log 4 at least.With after the suitable combination thing contacts, antiviral activity can keep about at least 0.5 hour, and preferably about at least 1 hour, and more preferably about at least two hours, about at least three hours, or about at least four hours.In some preferred embodiments, with after compound or composition contact, antiviral activity can keep about six to about eight hours.Lasting antiviral activity is owing to be present in due to the reservoir of the barrier layer of the lip-deep composition of handling or the non-volatile component in the film at least in part.The lasting employed method of antiviral effect of measuring will be discussed below.

[0083] therefore, method of the present invention is providing fast and wide spectrum control bacterium and to control fast and lastingly aspect viral be fruitful.Have been found that, utilize any safety and effective method, the method of typically utilizing skin to contact with suitable combination thing or composition, be reduced to less than about 4 by pH value skin, preferably less than about 3.75, and be more preferably less than approximately 3.5, most preferably, can give warm blooded animal skin with lasting antiviral benefit less than about 3.25.

[0084] can make bacterium and virally inactivated or be known effectively, but these compositions and method rely on the pH value of the active component of composition and/or composition, to realize control to viral and bacterium with the compound and the composition of its elimination.Find that surprisingly quick and broad spectrum of bacteria is controlled and lasting virus control can be by reducing surface pH value to obtaining less than about 4.Thus, compare with previous method and composition, this method provides the method for safety, gentleness and more effective control virus and bacterium.

[0085] this method is gentle for skin not only, and for the inanimate surfaces non-corrosiveness.Thus, the bacterium that solves on the inanimate surfaces and the effective ways of viral control problem are also provided.

[0086] this composition provides the effective and lasting deactivation to nonenveloped virus.Nonenveloped virus is including, but not limited to adenovirus, papovavirus, parvovirus, birnavirus, astrovirus, rotavirus, calicivirus (comprising Norwalk virus) and picornavirus (comprising rhinovirus, bone marrow poliomyelitis virus and hepatitis A virus).Said composition also can be controlled influenza virus and norovirus effectively and make its inactivation.

[0087] this method comprises: surface (especially warm blooded animal skin or food contacting surface) is contacted with the compound or the composition that surface p H value can be reduced to less than about 4 (for example about 2.5).Thus, this method is highly effective in following application: personal care applications (for example, lotion, shower gels, soap, shampoo and cleaning piece), industry and healthcare applications (for example sterilization of instrument, medical equipment and gloves), household cleaning (for example use, crust, for example floor, table top, bathtub, dish and soft cloth material, for example clothes and bedding), industry, pleasure-boat, sanatorium, school, doctor's office, dental clinic and hospital application (for example sterilization of instrument, medical equipment, uniform, long clothes and gloves).This method 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 method also provides lasting antiviral effect.

[0088] this method can the external and interior use of body.Externally be meant in lifeless object or on it, particularly to prevent virus disseminating therein be needed position or use, have on the lifeless object of hard or pressure release surface, 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.

[0089] this method comprises: make the surface and the pH value of skin can be reduced to less than about 4, preferably less than about 3.75, less than about 3.5, less than about 3.25, less than about 3.0, contact with the compound or the composition of reducing to about 2.5 pH value, and keep low skin pH value to continue to much about four hours, in some embodiments, continue to much about eight hours.With the amount of every square centimeter of surface at least 10 microgram compounds with compound administration in the surface.This method can be controlled broad spectrum of bacteria efficiently, comprise Gram-positive and Gram-negative bacteria, for example aurococcus, hog cholera Salmonella, Escherichia coli and Klebsiella, and make simultaneously the harmful virus of health rhinovirus inactivation or it is killed particularly, continue about four hours or longer time period prolonging.This method also can be controlled bacterium and the virus on the inanimate surfaces effectively.

[0090] especially, this method comprises: with of short duration mode contact surface, for example wash and wash, or the contact surface long period, for example, lotion application, emulsifiable paste, gel, powder or other solid or semisolid (need not wash), compound or composition can be reduced to surface p H value less than about 4, and more preferably less than about 3.75, continue to much about 5 hours a period of times, continue to much about eight hours in preferred embodiments, and about at least half an hour.

[0091] as hereinafter more discussing fully, the compound that can reduce surface p H value is including, but not limited to (a) organic acid, preferably for the firm acid in surface, and has about 1 to about 6 pKa, more preferably about 2 to about 5.5, most preferably about 2.5 to about 5, wherein pKa is at room temperature (25 ℃), the decimal base negative logarithm of the acidolysis constant of the acid in water, comprise organic polymeric acid, preferably can on skin surface, form the acid of substantive film, and have less than about 25 ℃,, and be more preferably less than about 15 ℃ glass transition temperature Tg preferably less than about 20 ℃; (b) to skin and other surperficial non-corrosive inorganic acid; (c) inorganic salt solution, the solution of salt MX for example, wherein M is a polyvalent cation, and X is an anion, makes MX (at 25 ℃) in water have the solvability of 0.1g/100ml at least, and the pH value of solution is less than about 6, preferably less than about 5, is more preferably less than about 4.5; (d) complex compound of aluminium, zirconium or aluminum-zirconium; (e) its mixture.

[0092] above-mentioned and other compound that can reduce skin pH value can be mixed in consumer's acceptable composition, be used for application to the effective and beauty treatment of skin.This composition can comprise other component, other antibacterial agent for example, for example triclosan, trichlorocarbanilide, peroxide, quaternary ammonium antibacterial agent, pyrithione and cosmetic preservative and similar compounds, its quantity accounts for 0% to about 5% of composition weight.In preferred embodiments, composition contains optional gelling agent.

[0093] composition has the pH value less than about 5, and can form the continuous basically film or the layer of non-volatile composition component on the processing surface.Several hrs after using, film or layer hold out against and are not removed from the processing surface.Especially, after ten water flushings, the composition component of effective dose be retained in handle on the surface, and after the flushing of three water, at least 50%, preferred at least 60% and more preferably at least 70% non-volatile composition component is retained on the handled surface.

[0094] in handling the embodiment of skin, " flushing " is meant 30 seconds of handled skin of gently rubbing, air-dry then skin under the condition of the running water that slowly flows (have about 30 ℃ extremely about 40 ℃ temperature).In handling the embodiment of inanimate surfaces, " flushing " is meant and contacts handled surface about 30 seconds under the condition of the running water that slowly flows (have about 30 ℃ to about 40 ℃ temperature), air-dry then surface.

[0095] after contacting for 30 seconds, this method demonstrates about 2 logarithm minimizing value at Gram-positive bacteria.After contacting for 30 seconds, this method also demonstrates about 2.5 logarithm minimizing value at Gram-negative bacteria.Except quick control Gram-positive and Gram-negative bacteria, this method also provides lasting virus control.

[0096] in skin and 30 second after suitable compound or composition contact, this method has further demonstrated about 4 logarithm minimizing value at the unsettled virus of acid (comprising rhinovirus serotype), the contact after about 5 hours, demonstrate at least 3 logarithm minimizing value at these sour unsettled viruses, and the contact after about 6 to about 8 hours, demonstrate about at least 2 logarithm minimizing value.This method still is soft, needn't be from surface flushing or wiping compound or composition.

[0097] according to the present invention, this bactericidal composition can further comprise hereinafter disclosed other optional components, for example hydrotropic agent, polyhydroxyl solvents, gelling agent, surfactant, pH value conditioning agent, vitamin, dyestuff, skin conditioning agent, spices and antimicrobial activity, for example phenol and quaternary ammonium antibacterial agent.Preferably, said composition does not contain the clean surface activating agent that on purpose adds, for example ionic surfactant.

[0098] according to method of the present invention, following compound can reduce skin pH value fully.

A. Organic acid

[0099] this method can be used organic acid to reduce surface p H value to the sufficient amount less than about 4, the lip-deep bacterium of controlling organic acid thus and being contacted and viral and make its inactivation.Organic acid can help to provide the control fast to the unstable virus of acid, and lasting virus control is provided.

[00100] in case be administered to the surface, human skin for example, surface pH value is reduced fully, to obtain lasting virus control.In preferred embodiments, the organic acid residual volume keeps from the teeth outwards, even after optional rinsing step, so that give lasting virus control.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.Even organic acid is fully fallen from surface washing basically, surface p H value is reduced fully, can control virus at least 0.5 hour.

[00101] especially, organic acid is applied to the surface, the pH value that life or inanimate surfaces are arranged that its quantity should be enough to organic acid is contacted is reduced to the degree that can obtain lasting virus control, promptly less than about 4.No matter whether rinse out organic acid or be retained on the contact-making surface, all can obtain this lasting virus control from contact-making surface.After using, organic acid keeps not dissociating at least in part, and when the dilution or using and flush period between the time also can keep like this.

[00102] described organic acid has about 1 to about 6 pKa, and preferably approximately 2 to about 5.5.In order to obtain whole benefit of the present invention, described organic acid has about 2.5 to about 5 pKa.This organic acid has enough acid strengths, thereby surface p H value is reduced to less than about 4.Preferably, organic acid is firm for handle surface, thereby increases durable antibacterial performance.

[00103] typically, organic acid is included in the composition, its quantity account for greatly composition weight 0.05% to about 15%, preferably approximately 0.1% to about 10%.In order to obtain whole benefit of the present invention, the organic acid amount that is present in the composition accounts for about 0.15% to about 6% of composition weight.In preferred embodiments, the organic acid mixture is included in the composition.The organic acid total amount is relevant with employed organic acid classification, and with specific acid or use acid characteristic relevant.

[00104] preferably, the organic acid that is included in this antiviral composition does not infiltrate the surface that it applied, for example, with the infiltration surface opposite, it keeps from the teeth outwards, and from the teeth outwards with other non-volatile composition component for example optional gelling agent and/or antimicrobial activity cambium or film.Therefore, the preferably hydrophobic organic acid of organic acid.

[00105] in one embodiment of the invention, organic acid has less than 1, preferably less than 0.75 log P.In order to obtain whole benefit of the present invention, organic acid has the logP less than 0.5.In this embodiment, the optional pure and mild organic acid of sterilization works synergistically, so that effective and lasting virus control to be provided.

[00106] in another embodiment, organic acid has 1 or bigger, for example 1 to about 100 log P.In this embodiment, the optional pure and mild organic acid of sterilization can be controlled nonenveloped virus effectively, and works synergistically, with the control broad spectrum of bacteria.

[00107] 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 optional sterilization alcohol, thereby provide to the lasting control of nonenveloped virus with to the control of broad spectrum activity bacterium.

[00108] 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).

[00109] has less than the organic acid of 1 log P water-fastly typically, for example have less than the about water solubilities of 0.5wt% at 25 ℃.Think have 1 or the organic acid of bigger log P water-soluble typically, for example have the water solubility of 0.5wt% at least at 25 ℃.

[00110] organic acid that uses in the method comprise monocarboxylic acid, polybasic carboxylic acid, have a plurality of carboxyls, polymeric acid or its mixture of phosphate radical, sulfonate radical and/or sulfate radical part.Except acid moieties, organic acid can also contain other parts, for example hydroxyl and/or amino.In addition, can use organic acid anhydride in the method as organic acid.Preferred organic acid is polybasic carboxylic acid, polymerization of carboxylic acid or its mixture.

[00111] in one embodiment, organic acid comprises and has structure RCO ₂The monocarboxylic acid of H, wherein R is C _1-10Alkyl, hydroxyl C _1-3Alkyl, halogen C _1-3The phenyl of alkyl, phenyl or replacement.Preferably, monocarboxylic acid is at 25 ℃ of water solubilities with about at least 0.05% weight.Alkyl can be replaced by phenyl and/or phenoxy group, and phenyl and phenoxy group can be replacements or unsubstituted.

[00112] non-limitative example of the monocarboxylic acid that uses in the present invention be acetate, propionic acid, sad, glycolic, lactic acid, benzoic acid, phenylacetic acid, phenoxyacetic acid, neat graceful acid, 2-, 3-or 4-hydroxybenzoic acid, the acid of N-anilide, neighbour, or rubigan acetate, neighbour, or parachlorophen-oxyacetic acid and composition thereof.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 acid of 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.

[00113] in another embodiment, organic acid comprises polybasic carboxylic acid.Polybasic carboxylic acid contains at least two and four carboxyls at the most.Except replacement and unsubstituted phenyl, polybasic carboxylic acid can also contain hydroxyl or amino.Preferably, polybasic carboxylic acid is at 25 ℃ of water solubilities with about at least 0.05% weight.

[00114] non-limitative example of the polybasic carboxylic acid that uses in the present invention comprises malonic acid, succinic acid, glutaric acid acid, adipic acid, pimelic acid, suberic acid, azelaic acid, decanedioic acid, fumaric acid, maleic acid, tartaric acid, malic acid, maleic acid, citric acid, aconitic acid and composition thereof.

[00115] acid anhydrides of polybasic carboxylic 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.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 thing contact that is combined, and helps to provide lasting antiviral activity thus.

[00116] in the 3rd embodiment, organic acid comprises polymerization of carboxylic acid, polymerization sulfonic acid, Sulfated polymer, 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 composition thereof.Preferably, polymeric acid can form firm film on skin surface, and has less than about 6, preferably less than about 5.5 pKa with less than about 25 ℃ of T _g,, and be more preferably less than about 15 ℃ glass transition temperature preferably less than about 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

[00117] polymeric acid is uncrosslinked or only very minimally is crosslinked.Therefore polymeric acid is water-soluble or is that water is dispersible at least.Polymeric acid typically by have at least one hydrophilic segment for example the ethylenically unsaturated monomer of carboxyl, carboxylic acid anhydrides, sulfonic acid and sulfate radical prepare.Polymeric acid can contain comonomer, and for example styrene or alkene are to improve the hydrophobicity of polymeric acid.

[00118] be used to prepare polyorganic acid monomer example including, but not limited to:

(a) contain the monomer of carboxyl, the for example unsaturated list or the polybasic carboxylic acid of mono-vinylization, 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 acids;

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

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

[00119] but polymeric acid can contain the unit of other copolymerization, i.e. the unsaturated comonomer of other mono-vinylization well known in the art is as long as polymer comprises at least 10%, preferred at least 25% monomeric unit that comprises acidic group in fact.In order to obtain whole benefit of the present invention, polymeric acid comprises at least 50%, more preferably at least 75% and at the most 100% the monomeric unit that comprises acidic group.Other copolymerizable unit for example can be styrene, 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 surface p H value, and give lasting antiviral activity.

[00120] polymeric acid can help to form from the teeth outwards the film or the layer of residual organic acid or other reduction skin pH value compound, and further promotion forms the more continuous layer of residual organic acid from the teeth outwards.Polymeric acid typically is used in combination with the compound of monocarboxylic acid and/or polybasic carboxylic acid or other reduction surface p H value.

[00121] 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.

[00122] 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/acrylic acid C20-30 Arrcostab cross-linked copolymer	(ULTREZ?20)
Acrylate/methacrylic acid behenyl alcohol polyethers 25 ester copolymers	(ACULYN?28)
		Acrylate/methacrylic acid stearyl alcohol polyethers 20 ester copolymers	(ACULYN?22)
Acrylate/methacrylic acid stearyl alcohol polyethers 20 ester cross-linked copolymers	(ACULYN?88)
		Acrylate copolymer	(CAPIGEL?98)
Acrylate copolymer	(AVALURE?AC)
		Acrylate/acrylic acid Palmitoleyl alcohol polyethers 25 ester copolymers	(SYNTHALEN?2000)
The ammonium acrylate copolymer
		PAA/ethenol copolymer
Sodium polymethacrylate
		Acrylamido oxypropyl trimethyl ammonium chloride/acrylate copolymer
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/acryloyl nitrogen copolymer

[00123] in a preferred embodiment of the invention, organic acid comprises one or more polybasic carboxylic acids, for example citric acid, malic acid, tartaric acid or any two kinds or all three kinds these sour mixtures, and the polymeric acid that comprises many carboxyls, for example homopolymers of acrylic or methacrylic acid and copolymer.

B. Inorganic acid

[00124] this method also can be used the non-corrosive inorganic acid in surface, replaces organic acid or uses with organic acid.Preferably, inorganic acid is firm to its application surface.Be similar to organic acid, inorganic acid can be present in the composition, be used for to surface applied, its quantity be composition about 0.05% to about 15% weight, preferably approximately 0.1% to about 10% weight.In order to obtain whole benefit of the present invention, the amount of inorganic acid is about 0.15% to about 5% of a composition weight.

[00125] at 25 ℃, inorganic acid has the pKa less than 6, preferably less than 5.5.In order to obtain whole benefit of the present invention, inorganic acid is at 25 ℃ of pKa that have less than 5.Do not limit the characteristic of inorganic acid, but inorganic acid must have enough acidity, thereby surface p H value is reduced to less than about 4, can influence the surface simultaneously sharply, for example corrode inanimate surfaces or stimulate the life surface.The example of inorganic acid is including, but not limited to phosphoric acid, pyrophosphoric acid, polyphosphoric acid, phosphorous acid and composition thereof, and similar non-corrosive inorganic acid.

C. Mineral salt

[00126] can use mineral salt to replace organic acid and/or inorganic acid or use with organic acid and/or inorganic acid, mineral salt comprise cation and counter ion, cation has 2,3 or 4 chemical valence, counter ion can with surface p H value for example skin pH value be reduced to less than about 4.According to the present invention, separately or with the mineral salt of organic acid and/or inorganic acid combination, the quantity of its existence should be enough to control the virus on institute's contact surface and make its inactivation.With organic acid and inorganic acids seemingly, by surface p H value being reduced to less than about 4, mineral salt can provide control fast to the unsettled virus of acid, and lasting virus control can be provided.

[00127] cation of mineral salt has 2,3 or 4 chemical valence, and can be for example magnesium, calcium, barium, aluminium, iron, cobalt, nickel, copper, zinc, zirconium and tin.Preferred cation comprises for example zinc, aluminium and copper.

[00128] anion of mineral salt including, but not limited to: bisulfate ion, sulfate radical, dihydrogen phosphate, phosphoric acid one hydrogen root, halogen ion be chlorion, iodide ion and bromide ion and nitrate anion for example.Preferred mineral salt comprise chloride and dihydric phosphate.

[00129] amount of the mineral salt that use according to this method as composition about 0.1% to about 5% weight, preferably approximately 0.2% to about 2% weight.In order to obtain whole benefit of the present invention, mineral salt are applied on the surface with about 0.3% the inorganic salt solution form that comprises composition to about 1% weight.

[00130] in a kind of nonrestrictive embodiment, mineral salt comprise divalent zinc salt.Describe divalent zinc salt in this article in detail, but should be appreciated that, can use similar multivalent metal salt similarly according to this method.Especially, in the present invention the divalent zinc salt of Shi Yonging can have machine or inorganic counter ions.In preferred embodiments, use divalent zinc ion or any other useful cation with the form of not chelating or not complexing, this can make more effectively contact surface of cation, and potentially deposition from the teeth outwards, to help effectively and controlling microbial enduringly.

[00131] yet, in some embodiments, organic counter ion and divalent zinc ion are Zn ^{+ 2}Complexing.Can use this embodiment, as long as counter ion can be reduced to skin pH value less than about 4, the preferred Zn of complexing ^{+ 2}Not complexing Zn with enough equilibrium amounies ^{+ 2}, to help to control effectively the microorganism on the skin.

[00132] preferred divalent zinc salt or other useful mineral salt have at least approximately water solubility of 0.1g (gram)/100ml (milliliter) water at 25 ℃, preferably at 25 ℃ of water solubilities with about 0.25g/100ml water.Can not use the water-fast form of zinc, zinc oxide for example because counter ion can not reduce skin pH value, and can not utilize zinc ion to help control microorganism on the skin basically.

[00133] in the most preferred embodiment, divalent zinc salt or other useful mineral salt are water solubilities, but hold out against surface (particularly skin) flushing, so that the lasting effect of killing the virus to be provided.Therefore, in the most preferred embodiment, counter ion reduces surface p H value effectively and continues about four hours or more hours, whether divalent zinc or other cation are firm for the surface, and comprise the aqueous solution of mineral salt or allow it to keep after using irrelevant from the teeth outwards from surface washing after using.

[00134] though the previous composition that comprises zinc salt has been illustrated the ability (when virus enters the epithelial cell of nose, oral cavity and pharyngeal mucosa) of zinc ion interruption virus replication; shortened the duration of common cold thus; but the present invention points to unexpected discovery: when suitable mineral salt (comprising zinc salt) were applied on the surface (particularly hand and food contacting surface), it avoided providing beyond thought benefit aspect the rhinovirus infection at the protection individuality.Therefore, the benefit of prophylaxis of viral infections can provide greater than shortening the protection level that infects the duration simply.

[00135] zinc salt that is used for this bactericidal composition is including, but not limited to having the divalent zinc salt that is selected from following counter ion: glucose acid group, acetate, chlorion, bromide ion, citrate, formate, phosphoglycerol root, iodide ion, lactate, salicylate, tartrate anion and composition thereof.

D. The complex compound of aluminium, zirconium and aluminum-zirconium

[00136] can use the complex compound of aluminium, zirconium or aluminum-zirconium to replace organic acid, inorganic acid and/or mineral salt or therewith use.This complex compound (separately or with organic acid, inorganic acid and/or mineral salt combination) is applied to the surface, and its quantity should be enough to skin pH value is reduced to less than about 4, thus viral on the control surface and make its inactivation.With organic acid, inorganic acid and inorganic salts seemingly, these complex compounds can provide the quick control to the unsettled virus of acid, and after being applied to the surface, and the persistent virus control of about four hours or more hours can be provided.

[00137] complex compound of aluminium, zirconium and aluminum-zirconium polymerization typically in itself, comprise hydroxylic moiety, and have anion, such as, but be not limited to: sulfate radical, chlorion, chlorine hydroxyl, alumformate, lactate, benzyl sulfonate radical or phenylbenzimidazole sulfonic acid root.The exemplary classification of useful complex compound is including, but not limited to hydroxyhalides, zirconyl oxyhalides oxygen zirconium, hydroxyl halogenation oxygen zirconium and composition thereof.These complex compounds are acid typically in essence, and the composition that has less than about 5 pH value is provided thus, and typically have about 2 to about 4.5, preferably approximately 3 to about 4.5 pH value.Correspondingly, complex compound can be reduced to the pH value of skin less than about 4.

[00138] exemplary aluminium compound comprises aluminium chloride and has general formula Al ₂(OH) _xQ _yXH ₂The hydroxyhalides of O, wherein Q is chlorine, bromine or iodine; X is about 2 to about 5; X+y is about 6, and wherein x and y are unnecessary is integer; X is about 1 to about 6.Exemplary zirconium compounds comprises zirconium oxonium salt and zirconium hydrogen-oxygen salt, is also referred to as oxygen zirconates and hydroxyl oxygen zirconates, and by universal experience formula ZrO (OH) _2-nz-L _zRepresentative wherein changes between the z from about 0.9 to about 2, and unnecessary be integer; N is the chemical valence of L; 2-nz is more than or equal to 0; L is selected from halogen ion, nitrate anion, sulfamic acid root, sulfate radical and composition thereof.

[00139] therefore, exemplary complex compound including, but not limited to: polymeric aluminum chloride, tetrahydroxy chlorination aluminum-zirconium, with many chlorine hydroxyl aluminum-zirconium, trichlorine hydroxyl aluminum-zirconium, eight chlorine hydroxyl aluminum-zirconium, sesquialter chlorination hydroxy Al, sesquialter chlorination hydroxy Al PG, chlorination hydroxy Al PEG, the eight chlorine hydroxy Al zirconium glycine complexes of glycine complexing.Pentachloro-hydroxy Al zirconium glycine complexes, tetrachloro hydroxy Al zirconium glycine complexes, trichlorine hydroxy Al zirconium glycine complexes, chlorine hydroxy Al zirconium PG, zirconyl hydroxychloride, dichloride hydroxy Al, dichloride hydroxy Al PEG, dichloride hydroxy Al PG, sesquialter chlorination hydroxy Al PG, aluminium chloride, pentachloro-hydroxy Al zirconium and composition thereof.Many other useful compounds listed in following in: WO 91/19222 and CTFA Cosmetic IngredientHandbook, The Cosmetic, Toiletry and Fragrance Association, Inc., Washington, D.C, p.56,1988, hereinafter, introduce CTFA Handbook as a reference by list of references in this article.

[00140] preferred compound is and amino acid for example the chlorination aluminum-zirconium and the aluminum chlorohydrate of glycine complexing.Preferred aluminium-zirconium chloride glycine complexes has about 1.67 to about 12.5 aluminium (Al) and the total metal (Al+Zr) of zirconium (Zr) ratio and about 0.73 to about 1.93 and the ratio of chlorine.

[00141] typically, by organic acid, inorganic acid, mineral salt, zinc and/or aluminium complex are incorporated in the composition, then composition are applied to the surface and carry out this method.In this composition, the carrier of organic acid, inorganic acid, mineral salt and zinc and/or aluminium complex comprises water.Composition can be to rinse out or leave-on composition, as long as the surface of contact has the pH value less than about 4.

[00142] bactericidal composition 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.

[00143] quantity that exists of optional components should be enough to carry out their expectation function, and can influence the antibacterial effect of composition sharply, especially can influence layer or film that the non-volatile component of synergistic effect that the optional pure and mild organic acid of sterilization provided or composition forms sharply on the processing surface.Optional component typically accounts for 0% to about 50% of composition weight respectively or altogether.

[00144] Ren Xuan component is including, but not limited to the optional components well known by persons skilled in the art of: hydrotropic agent, many hydroxyls solvent, sterilization alcohol, gelling agent, antimicrobial activity, surfactant, dyestuff, spices, pH value conditioning agent, thickener, viscosity modifier, foam stabiliser, chelating agent, skin conditioning agent, softening agent, preservative, buffer, antioxidant, chelating agent, opacifier, Babassuamidopropylamine and similar classification.

[00145] preferably, be used to reduce the pH value of composition of skin pH value 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 is used to reduce the composition of skin pH value is approximately 2 to less than about 5, is preferably about 2.5 to about 4.5.

Optional component

Antibacterial agent

[00146] in composition, can have the antibacterial agent that is used to reduce surface p H value, (if any) its quantity account for composition weight 0.1% to about 5%, preferably approximately 0.1% to about 2% weight, and more preferably about 0.3% to about 1% weight.

[00147] Ren Xuan antimicrobial activity can be for example phenol and the phenol type compound of hydrogen peroxide or benzoyl peroxide, three halogen diphenylurea, quaternary ammonium compound, ethoxylation of biguanides (for example Chlorhexidine digluconate), biphenol compound, 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).Preferably, Ren Xuan antibacterial agent is following illustrational phenol and biphenol compound.

[00148] compound by the following classification that is used singly or in combination illustrates the optional antibacterial agent that is used for the present invention:

(1) phenol antibacterial agent

(a) 2-xenol compound

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

[00149] 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.

[00150] in particularly preferred embodiments, Y is a chlorine, and m is 0, and n is 0, and o is 1, and r is 2, and p is 0.

[00151] the 2-xenol compound that is particularly useful has following array structure:

It has generally acknowledged title triclosan, and the coml trade name is IRGASAN DP300, is obtained from Ciba Specialty Chemicals Corp., Greensboro, NC.Another useful 2-xenol compound 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 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.Halogen is bromine or is preferably chlorine.

[00152] object lesson of phenol derivatives is including, but not limited to chlorophenols (neighbour, between, right), chlorophenesic acid, p-nitrophenol, picric acid, xylenols, to between chloro--xylenols, cresols (neighbour, between, right), 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) biphenol compound

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 biphenol compound is hexachlorophene, tetra-chloro-phenol, antiphen, 2,3-dihydroxy-5,5 '-two chloro diphenyl sulfides, 2,2 '-dihydroxy-3,3 ', 5,5 '-tetrachloro diphenyl sulfide, 2,2 '-dihydroxy-3,5 ', 5,5 ', 6,6 '-chlordene diphenyl sulfide and 3,3 '-two bromo-5,5 '-two chloro-2,2 '-dihydroxy diphenylamine.Other biphenol compound is listed in U.S. Pat 6,436, and in 885, this paper is introduced into as a reference.

(2) quaternary ammonium antibacterial agent

[00153] effectively the quaternary ammonium antibacterial agent has following general structural 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 form 5 or 6 yuan of aliphatic or aromatic rings with nitrogen-atoms.Preferably, whole ammonium cations of antibacterial agent partly have at least 165 molecular weight.

[00154] 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.Remaining substituting group on the quaternary nitrogen atoms (non-above substituting group) 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, and this ring system both can be a for example piperidyl of aliphatic, also can be for example pyridine radicals of aromatic hydrocarbons.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 the halogen ion, for example, and chlorion, bromide ion or iodide ion, methylsulfate and ethyl sulphate.

[00155] 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, ethyl sulphate or p-methyl benzenesulfonic acid root.Alkyl R ₁₂And R ₁₃Can be straight or branched, straight chain preferably.

[00156] 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 antibacterial agent that is particularly useful comprises dialkyl group (C ₈-C ₁₀) alkyl dimethyl ammonium chloride (for example, Quaternium 24), zephiran (for example, benzalkonium chloride and myristyl dimethyl benzyl ammonium chloride), alkyl methyl dodecylbenzyl ammonium chloride, methyl dodecyl dimethylbenzene-two-(trimethyl ammonium) chloride, benzethonium chloride, 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.

[00157] other example of quaternary ammonium antibacterial agent is including, but not limited to alkyl ammonium halide, for example the 16 basic trimethylammonium bromides of washing; Alkylaryl ammonium halide, for example octadecyl dimethyl benzyl ammonium bromide; N-alkyl pyridine halide, for example N-cetyl bromination pyridine; Or the like.Other suitable quaternary ammonium antibacterial agent has acid amides, ether or ester moiety, for example Octylphenoxy ethoxyethyl group dimethyl benzyl ammonium chloride, 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, dodecylbenzyl trimethyl ammonium chloride, chlorination dodecylbenzyl trimethyl ammonium chloride, or the like.

[00158] concrete quaternary ammonium antibacterial agent is including, but not limited to mountain Yu base benzyl dimethyl ammonium chloride, cetalkonium chloride, bromination cetearyl ammonium, western bent ammonium methyl sulphate, cetylpyridinium chloride, Laura bromine ammonium, Lauralkonium Chloride, lapirium chloride, dodecyl chlorination pyridine, myristyl benzyl dimethyl ammonium chloride, oil base benzyl dimethyl ammonium chloride and iso stearyl ethyl alkyl dimethyl ammonium chloride.Preferred quaternary ammonium antibacterial agent comprises benzalkonium chloride, benzethonium chloride, cetyl bromination pyridine and Methylbenzethonium Chloride.

(3) N-anilide and biguanides antibacterial agent

[00159] effectively N-anilide and biguanides antibacterial agent including, but not limited to: neko, diphenylurea, salicylamide, tribromosalicylanilide, tetrachloro are for salicylaniline, Flusalan, chlorhexidine gluconate, chlorhexidine hydrochloride and composition thereof.

Sterilization alcohol

[00160] thus being used to reduce the useful composition that surface p H value produces lasting bacterium and virus control in the method also can comprise the optional sterilization alcohol of (if any) 10% to about 90% weight.Preferred compositions comprises optional sterilization alcohol, and its quantity is approximately 10% to about 70% weight, and more preferably about 20% to about 65% weight.

[00161] term that uses in this article " sterilization alcohol " is the water-soluble alcohol that contains 1 to 6 carbon atom, i.e. C ₁-C ₆Alcohol.Sterilization alcohol is including, but not limited to methyl alcohol, ethanol, propyl alcohol and isopropyl alcohol.

The component that other is optional

[00162] surfactant can be contained in the composition, is used for reducing surface (especially skin) pH value, its comprise quantity account for greatly composition weight 0% to about 15%, typically account for 0.1% to about 10%.More typically, if present, composition comprises about 0.2% surfactant to about 7% weight.Optional surfactant is stable under the pH of composition value, and with other component contradiction not that is present in the composition.

[00163] surfactant can be anionic surfactant, cationic surface active agent, nonionic surface active agent or compatible surfactant mixtures.Surfactant also can be the surfactant of both sexes, and it has anion or cationic performance, and this depends on the pH value of composition.

[00164] therefore, composition can contain and have hydrophobic parts and (for example comprise about 8 carbochains to about 30 carbon atoms, especially about 12 to about 20 carbon atoms) anionic surfactant, and the part of further possess hydrophilic property, for example sulfate radical, sulfonate radical, carbonate, phosphate radical or carboxylate radical.Hydrophobic carbochain usually is an etherificate, for example with ethylene oxide or propylene oxide etherificate, to give specific physical property, for example increases the water solubility of anionic surfactant or reduces surface tension.

[00165] suitable anionic surfactant is including, but not limited to being called as following compounds category: alkyl sulfate; alkyl ether sulfate; alkylether sulfonate; the sulfuric ester of alkyl phenoxy polyethylene glycol oxide ethanol; alpha-alkene sulfonate; β-alkoxyalkyl sulfonate; alkylaryl sulfonates; alkyl glycerol monoesters sulphate; alkyl glycerol monoesters sulfonate; alkyl carbonate; the alkyl ether carboxy acid salt; fatty acid; sulfosuccinate; sarcosinate; octyl phenol polyethers or nonoxinol phosphate; taurate; the taurate of aliphatic series; fatty acid amide polyethylene glycol oxide sulphate; isethionate; acyl glutamate; alkyl sulfoacetate; the peptide of acidylate; acyl-lactate; anionic fluorine-containing surfactant and composition thereof.Other anion surfactant list in following in: McCutcheon ' s Emulsifiers and Detergents, 1993Annuals, (McCutcheon ' hereinafter s), McCutcheon Division, MC Publishing Co., Glen Rock, NJ, pp.263-266, this paper is introduced into as a reference.The classification of many other anion surfactants and anion surfactant is disclosed in U.S. Pat 3,929,678 and United States Patent (USP) publication number 2002/0098159 in, this paper is incorporated herein by reference each.

[00166] the concrete and non-limiting classification of the anionic surfactant that can use in the present invention is including, but not limited to C ₈-C ₁₈Alkylsulfonate, C ₈-C ₁₈Alkyl sulfate, C ₈-C ₁₈Soap, has the C of one or two mole of ethoxylation ₈-C ₁₈Alkyl ether sulfate, C ₈-C ₁₈Amino alcohol oxide, C ₈-C ₁₈Alkanoyl sarcosinate, C ₈-C ₁₈Sulfosalicylic acetate, C ₈-C ₁₈Sulfosuccinate, C ₈-C ₁₈Alkyl diphenyl ether disulfonate, C ₈-C ₁₈Alkyl carbonate, C ₈-C ₁₈Alpha-alkene sulfonate, methyl ester sulfonate and composition thereof.C ₈-C ₁₈Alkyl contains eight to 18 carbon atoms, and can be (for example 2-ethylhexyl) of straight chain (for example lauryl) or side chain.The cation of anionic surfactant can be alkali metal (preferred sodium or potassium), ammonium, C ₁-C ₄Alkylammonium (single, two-, three-) or C ₁-C ₃Alkanol ammonium (single, two-, three-).Can use lithium and alkaline earth metal cation (for example magnesium), but not be preferred.

[00167] concrete surfactant comprises but is not limited to: lauryl sulfate, octyl sulfate, 2-ethylhexyl sulphate, decyl sulfate, tridecyl sulphate, cocoa butter, Hamposyl L salt, the lauryl sulfosuccinate, straight chain C 10 diphenyl ether disulfonates, the lauryl sulfosuccinate, lauryl ether sulfate (1 and 2 mole ethylene oxide), tetradecyl sulfate, oleate, stearate, resinate, ricinate, cetyl sulphate and similar surfactant.Other example of surfactant can find in following: ＂ CTFACosmetic Ingredient Handbook, ＂ J.M.Nikitakis, ed., The Cosmetic, Toiletry and Fragrance Association, hie., Washington, D.C. (1988) (CTFA Handbook hereinafter), 10-13,42-46 and 87-94 page or leaf, this paper is introduced into as a reference.

[00168] composition also can contain nonionic surface active agent.Typically, nonionic surface active agent has hydrophobic group, for example chain alkyl or alkylating aryl and comprise the ethyoxyl and/or the propoxyl group hydrophilic chain partly of sufficient amount (promptly 1 to about 30).Examples of nonionic surfactants comprises the alkyl phenol of ethoxylation, ethoxylation and polyglycol ether propenoxylated fatty alcohol, methyl glucose, the polyglycol ether of sorbitol, ethylene oxide-oxypropylene block copolymer, aliphatic series (C ₈-C ₁₈) hydroxyethylation ester, ethylene oxide and long-chain amine or the condensation product of acid amides and composition thereof of acid.

[00169] exemplary nonionic surface active agent is including, but not limited to methyl glucoside ether-10, the two stearates of PEG-20 methyl glucose, PEG-20 methyl glucose stearic acid sesquialter ester, C _11-15The nonyl phenol of alkanol polyethers-20, cetanol polyethers-8, cetanol polyethers-12, dodecyl phenol polyethers-12, laureth-15, PEG-20 castor oil, polysorbate 20, stearyl alcohol polyethers-20, polyoxyethylene-10 cetyl ether, polyoxyethylene-10 stearoyl ether, polyoxyethylene-20 cetyl ether, polyoxyethylene-10 oleoyl ether, polyoxyethylene-20 oleoyl ether, ethoxylation, the octyl phenol of ethoxylation, the dodecylphenol of ethoxylation or the aliphatic series (C of ethoxylation ₆-C ₂₂) alcohol (comprising 3 to 20 ethylene oxide parts), polyoxyethylene-20 isocetyl ether, polyoxyethylene-23 glycerine laurate, polyoxyethylene-20 glyceryl stearate, the PPG-10 methyl glucose ether, the PPG-20 methyl glucose ether, polyoxyethylene-20 anhydro sorbitol monoesters, polyoxyethylene-80 castor oil, polyoxyethylene-15 tridecyl ether, polyoxyethylene-6 tridecyl ether, laureth-2, laureth-3, laureth-4, the PEG-3 castor oil, PEG 600 dioleates, PEG 400 dioleates and composition thereof.

[00170] many other nonionic surface active agent be disclosed in following in: McCutcheon ' s, 1-246 page or leaf and 266-272 page or leaf; At CTFA InternationalCosmetic Ingredient Dictionary, Fourth Ed., Cosmetic, Toiletry andFragrance Association, Washington is in the 1-651 page or leaf of D.C. (1991) (hereinafter CTFA Dictionary); With at CTFA Handbook, in the 86-94 page or leaf, each is incorporated herein by reference this paper with it.

[00171] except anionic and nonionic surface active agent, in composition, can also use surfactants cationic, both sexes.Effectively cationic surface active agent comprises those with following structural:

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

[00172] preferably, R ₁₅Be to have about 12 alkyl to about 22 carbon atoms; R ₁₆Be H or have 1 alkyl to about 22 carbon atoms; R ₁₇And R ₁₈Be H independently or have 1 alkyl to about 3 carbon atoms.More preferably, R ₁₅Be to have about 12 alkyl, R to about 22 carbon atoms ₁₆, R ₁₇And R ₁₈Be H or have 1 alkyl to about 3 carbon atoms.

[00173] other useful cationic surfactant comprises amino-acid amides, wherein in said structure, and R ₁₀Also can be R ₁₉CONH-(CH ₂) _n, R wherein ₁₉Be to have about 12 alkyl to about 22 carbon atoms, n is 2 to 6, more preferably 2 to 4, and 2 to 3 integer most preferably.The non-limitative example of these cationic surfactants comprises: stearoyl amido propyl group PG-dimethyl chlorination ammonium phosphate, mountain Yu amido propyl PG alkyl dimethyl ammonium chloride, stearoyl amido propyl group ethyl dimethyl ethyl ammonium sulfate, stearoyl amido propyl-dimethyl (myristyl acetate) ammonium chloride, stearoyl amido propyl-dimethyl cetostearyl alcohol ammonium tosylate, stearoyl amido propyl group dimethyl ammonium chloride, stearoyl amido propyl-dimethyl ammonium lactate and composition thereof.

[00174] non-limitative example of quaternary cationics comprises and is selected from following those: cetyl ammonium chloride, cetyl bromination ammonium, lauryl chlorination ammonium, lauryl bromination ammonium, stearoyl chlorination ammonium, the stearoyl ammonium bromide, the cetyl alkyl dimethyl ammonium chloride, cetyl dimethyl ammonium bromide, the lauryl dimethyl ammonium chloride, the lauryl dimethyl ammonium bromide, the stearoyl dimethyl ammonium chloride, stearoyl dimethyl ammonium bromide, hexadecyltrimethylammonium chloride, the 16 basic trimethylammonium bromides of washing, lauryl trimethyl ammonium chloride, the lauryl trimethylammonium bromide, stearyl trimethyl ammonium chloride, the stearoyl trimethylammonium bromide, the lauryl dimethyl ammonium chloride, stearoyl dimethyl cetyl two tallow base dimethyl ammonium chlorides, two (cetyl) ammonium chloride, two (cetyl) ammonium bromide, dilauryl ammonium chloride, the dilauryl ammonium bromide, distearyl ammonium chloride, the distearyl ammonium bromide, two (cetyl) ammonio methacrylate, two (cetyl) methyl ammonium bromide, the dilauryl ammonio methacrylate, dilauryl methyl ammonium bromide, the distearyl ammonio methacrylate, distearyl methyl ammonium bromide and composition thereof.

[00175] other quaternary ammonium salt comprises wherein C ₁₂-C ₃₀Alkyl carbon chain stems from tallow fatty acid or comes from those of fatty acid distribution of coconut oil.Term " tallow " is meant that it has C usually derived from the alkyl of tallow fatty acids (the normally tallow fatty acids of hydrogenation) ₁₆To C ₁₈The mixture of the alkyl chain of scope.Term " cocounut oil " is meant the alkyl derived from fatty acid distribution of coconut oil, and it has C usually ₁₂To C ₁₄The mixture of the alkyl chain of scope.Quaternary ammonium salt example derived from these tallows and cocounut oil source comprises two tallow base dimethyl ammonium chlorides, two tallow base dimethyl methyl ammonium sulfate, two (hydrogenated tallow) dimethyl ammonium chloride, two (hydrogenated tallow) dimethyl acetic acid ammonium, two tallow base dipropyl ammonium phosphate, two tallow base dimethyl ammonium nitrate, two (cocounut oil alkyl) dimethyl ammonium chloride, two (cocounut oil alkyl) dimethyl ammonium bromide, tallow ammonium chloride, cocounut oil ammonium chloride and composition thereof.Example with quaternary ammonium compound of alkyl and ester bond is two tallow acyloxy ethyl alkyl dimethyl ammonium chlorides.

[00176] amphoteric surfactant (being both sexes and zwitterionic surfactant) can be described as widely the second month in a season with straight or branched aliphatic group and the derivative of tertiary amine, one of them aliphatic substituting group contains about 8 to about 18 carbon atoms, at least one aliphatic substituting group contains anionic water solubilizing group, for example carboxyl, sulfonate radical or sulfate radical.

[00177] more particularly, amphoteric surfactant classification comprises sarcosinate and the taurate with following conventional structure formula:

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

[00178] another classification of the surfactant of both sexes is the sulfosuccinate acid amides with following structural:

[00179] can also use the amphoteric surfactant of following classification:

Alcohol both sexes glycinate

Alcohol both sexes carboxyl glycinate

Alcohol both sexes propionate

Alcohol both sexes carboxyl propionate

Alcohol both sexes propyl sulfonic acid salt

The alkyl amide CAB

Alkyl amide propyl hydroxy sulphonic acid betaine

Alkyl aminopropionic acid salt

Alkyl imido grpup propionate

Other classification of amphoteric surfactant comprises phosphoric acid betaine and phosphorous acid betain.

[00180] is used for the present invention's amphoteric surfactant concrete and non-limitative example is a cocounut oil N methyl taurine sodium; oleoyl N methyl taurine sodium; appropriate youngster's oleic acid N methyl taurine sodium; palmityl N methyl taurine sodium; cocoa base dimethyl carboxyl methyl betaine; lauryl dimethyl carboxyl methyl betaine; lauryl dimethyl carboxy ethyl betain; cetyl dimethyl carboxyl methyl betaine; lauryl-two-(2-ethoxy) carboxyl methyl betaine; oleoyl dimethyl γ carboxyl CAB; lauryl-two-(2-hydroxypropyl)-carboxy ethyl betain; cocoa base amide groups dimethyl propyl sulphonic acid betaine; stearoyl amide groups dimethyl propyl sulphonic acid betaine; lauryl acylamino-two-(2-ethoxy) propyl sulfonic acid betain; oleamide PEG-2 sulfo-succinic acid disodium; TEA oleamide PEG-2 sulfosuccinate; oleamide MEA sulfo-succinic acid disodium; oleamide MIPA sulfo-succinic acid disodium; castor oil acid amides MEA sulfo-succinic acid disodium; endecatylene acid amides MEA sulfo-succinic acid disodium; wheat-germ oil acid amides MEA sulfo-succinic acid disodium; wheat-germ oil acid amides PEG-2 sulfo-succinic acid disodium; isostearoyl amido MEA sulfo-succinic acid disodium; cocoa base both sexes glycinate; cocoa base both sexes carboxyl glycinate; lauryl both sexes glycinate; lauryl both sexes carboxyl glycinate; octyl group both sexes carboxyl glycinate; cocoa base both sexes propionate; cocoa base both sexes carboxyl propionate; lauryl both sexes carboxyl propionate; octyl group both sexes carboxyl propionate; dihydroxy ethyl tallow glycinate; cocamidopropyl disodium 3-hydroxypropyl phosphoric acid betaine; lauric acid myristic acid amide groups disodium 3-hydroxypropyl phosphoric acid betaine; lauric acid myristic acid amide groups glyceryl phosphoric acid betaine; lauric acid myristic acid amide groups carboxyl disodium 3-hydroxypropyl phosphoric acid betaine; the single sodium phosphorous acid of cocoa base amidopropyl betain; the single sodium phosphorous acid of lauric acid myristic acid amidopropyl betain and composition thereof.

[00181] effectively amphoteric surfactant also comprises amine oxide.Amine oxide has the conventional structure formula, and wherein hydrophilic segment contains the nitrogen-atoms that combines with oxygen atom (having semi-polar bond).

[00182] R ²², R ²³And R ²⁴Can be to have 1 saturated or undersaturated branched-chain or straight-chain alkyl or thiazolinyl to about 24 carbon atoms.Preferred amine oxide contains at least one R group, and it is the alkyl chain of 8 to 22 carbon atoms.The non-limitative example of amine oxide comprises alkyl dimethyl amine oxide for example decyl amine oxide, cocounut oil amine oxide, myristyl dimethyl oxidation ammonium and palm amine oxide.Also usefully alkyl amino propylamine oxide, for example cocoamide base propylamine oxide and stearoyl amido propylamine oxide.

The non-limitative example of the preferred surfactants of [00183] using in composition comprises and is selected from following those: alkyl sulfate; Alkyl ether sulfate; Alkylbenzenesulfonate; Alpha-alkene sulfonate; Uncle or secondary alkyl sulfonate; Alkylphosphonic; Acyl taurine salt; The sulfo-succinic acid alkyl ester salt; Fatty alkyl sulfoacetate salt; The fatty acid of sulfonation; Alkyl trimethyl ammonium chloride and ammonium bromide; Dialkyl group dimethyl ammonium chloride and ammonium bromide; Alkyl dimethyl amine oxide; Alkylamidoalkyl propylamine oxide; Alkyl betaine; The alkylamidoalkyl CAB; And composition thereof.Preferred surfactant comprises and is selected from following those: alkyl sulfate; Alkyl ether sulfate; Alkylbenzenesulfonate; Alpha-alkene sulfonate; Uncle or secondary alkyl sulfonate; Alkyl dimethyl amine oxide; Alkyl betaine; And composition thereof.

[00184] if there is hydrotropic agent, its exist quantity account for composition weight about 0.1% to about 30%, preferably approximately 0.1% to about 20%.More preferably, composition can contain about 2% hydrotropic agent to about 15% weight.

[00185] hydrotropic agent is the compound with ability of the solvability that strengthens other compound.The hydrotropic agent that uses in the present invention lacks surfactant properties, and short-chain alkylarenesulfonate typically.Hydrotropic object lesson 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 agent comprises poly-sodium naphthalene sulfonate, kayexalate, methyl naphthalene sulfonic acid sodium, sodium camphorsulfonate and disodium succinate.

[00186] if there is polyhydroxyl solvents, its exist quantity account for composition weight about 0.1% to about 50%, preferably approximately 5% to about 40%.In order to obtain whole benefit of the present invention, the amount of polyhydroxyl solvents account for composition about 10% to about 30% weight.Opposite with sterilization alcohol, polyhydroxyl solvents is very low for the contribution of the antibacterial effect of composition, if any.

[00187] term " polyhydroxyl solvents " that uses in this article is to contain 2 to 6 and the organic compound of the water solubility of two or three hydroxyls typically.Term " water solubility " be meant 25 ℃, per 100 the gram water in many hydroxyls solvent have at least 0.1 the gram polyhydroxyl solvents water solubility.Water solubility to polyhydroxyl solvents does not have the upper limit, and for example, polyhydroxyl solvents and water can dissolve in all proportions.

[00188] therefore, the term polyhydroxyl solvents comprises glycol, the three pure and mild polyalcohols of water solubility.The object lesson of hydroxyl solvent is including, but not limited to ethylene glycol, propane diols, glycerine, diethylene glycol, dipropylene glycol, tripropylene glycol, hexylene glycol, butanediol, 1,2,6-hexanetriol, sorbitol, PEG-4 and similar polyol.

[00189] composition also can contain about 0.1% to about 5% weight, the preferred 0.1% optional gelling agent (if any) to about 3% weight.More preferably, composition can contain about 0.1% gelling agent to about 2.5% weight.Composition can contain the gelling agent of sufficient amount, so that composition is to be applied to skin or other surperficial viscous liquid, gel or semisolid of going up and rubbing in the above easily.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 required composition viscosity or denseness is provided.

[00190] term " gelling agent " that here and hereinafter uses is meant that the compound that can improve aqueous composition viscosity maybe can be converted into aqueous composition gel or semisolid compound.Therefore, gelling agent can be organic matter in itself, for example, and natural gum or synthetic polymer, or can be inorganic matter in itself.

[00191] 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, C _9-15Alcohol, calcium acetate, calcium alginate, the calcification carrageenan, calcium chloride, octanol, carboxymethyl hydroxyethyl cellulose, CMHPG, carrageenan, cellulose, cellulose gum, cetostearyl alcohol, cetanol, corn starch, hard gum, dextrin, diphenyl methylene sorbitol, ethylene hydrogenated tallow acid amides, the ethylene oleoyl, ethylenebisstearamide, fruit pectin, gel, guar gum, the guar gum hydroxypropyl-trimethyl ammonium chloride, hectorite, hyaluronic acid, hydrated silica, HBMC, hydroxyethylcellulose, hydroxyethyl ethylcellulose, ethoxy stearmide-MIPA, hydroxypropyl cellulose, hydroxypropyl guar gum, hydroxypropyl methylcellulose, different cetanol, isooctadecane alcohol, karaya, kelp ashes, laruyl alcohol, locust bean gum, aluminium-magnesium silicate, magnesium silicate, magnesium trisilicate, methoxyl group PEG-22/ dodecyl glycol copolymer, methylcellulose, microcrystalline cellulose, imvite, tetradecanol, oat meal, oleyl alcohol, palm kernel alcohol, 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 aluminosilicate, sodium sulphate, stearic bentonite, stearic hectorite, octadecanol, tallow alcohol, the TEA-hydrochloride, bassora gum, tridecanol, the tromethamine aluminium-magnesium silicate, wheat flour, wheaten starch, xanthans, polyvinylpyrrolidone and their derivative, vinyl ethers derivative (methyl vinyl ether, ethyl vinyl ether, butyl vinyl ether, IVE, polymethyl vinyl ether/maleic acid), polymer and methacrylate copolymer based on quaternised vinyl pyrrolidone/quaternised dimethyl aminoethyl pyrrolidones, caprolactam/vinyl pyrrolidone dimethylaminomethyl X 4460, vinyl pyrrolidone/dimethylaminomethyl ethyl acrylate copolymer, the acid of guar gum stable and naturally occurring derivative and modified guar, the xanthans of modifying or replacing, carboxy-propyl cellulose and composition thereof.

[00192] other non-limitative example of following gelling agent mainly works by the non-water section thickening that makes composition:

[00193] abienol, acryloyl linoleic acid, behenic acid aluminium, aluminium octoate, dilinoleic acid aluminium, double stearic acid aluminium, isostearic acid/lauric acid/palmitic acid or aluminum stearate, isostearic acid/myristic acid aluminium, 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, behenamide, behenyl alcohol, butadiene/acrylonitrile copolymer, C _29-70Acid behenic acid calcium, calcium stearate, candelila wax, palm wax, ceresine, cholesterol, the cholesteryl hydroxy stearic acid ester, lauric alcohol, copal, diglycerol base stearate malate, dihydroabietyl alcohol, dimethyl lauramide oleate, dodecanedioic acid/cetostearyl alcohol/glycol copolymer, the mustard acid amides, ethyl cellulose, glyceryl triacetyl hydroxy stearic acid ester, glyceryl triacetyl ricinate, ethylene glycol bisthioglycolate behenic acid ester, 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; HPO; hydrogenated coconut benevolence oil; Parleam; oil with hydrogenated soybean; hydrogenated tallow amide; hydrogenated tallow glyceride; hydrogenated vegetable glyceride; hydrogenated vegetable glyceride; hydrogenated vegetable oil; hydroxypropyl cellulose; isobutene/isoprene copolymer; isocetyl stearyl stearate; Japan tallow; jojoba wax; lanolin alcohol; lauramide; the methyl dehydroabietate; the hydrogenated methyl rosinate; the methyl rosinate; methyl styrene/vinyl toluene copolymer; microwax; cover smooth sour paraffin; lignite wax; the myristyl eicosanol; the myristyl octadecanol; vaccenic acid/copolymer-maleic anhydride; octyl group dodecyl stearyl stearate; oleamide; oleostearin; ouricury wax; oxidic polyethylene; ceresine; palm kernel alcohol; paraffin hydrocarbon; pentaerythrite hydrogenated rosins acid esters; the pentaerythrite rosinate; pentaerythrite four abietates; pentaerythrite Si behenic acid ester; pentaerythrite four caprylates; pentaerythrite four oleates; pentaerythritol tetrastearate; phthalic anhydride/glycerine/glycidyl decylate copolymer; phthalic acid/trimellitic acid/glycol copolymer; polybutene; polybutylene terephthalate; poly-cinene; polyethylene; polyisobutene; polyisoprene; polyvinyl butyral resin; the polyethylene laurate; the propane diols dicaprylate; propylene glycol dicaprate; propane diols two different pelargonates; the 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; stearic bentonite; stearic hectorite; stearmide; the two stearates of stearmide DEA-; stearmide DIBA-stearate; stearmide MEA-stearate; stearone; octadecanol; stearoyl mustard acid amides; the stearoyl stearate; stearoyl 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 myristate; zinc neodecanoate; abietic acid zinc; zinc stearate and composition thereof.

[00194] the exemplary gelling agent that uses in the present invention including, but not limited to:

Polyethylene glycol and propane diols and water	(ACULYN?44)
		Acrylic acid dimethyl taurine ammonium/VP copolymer	(ARISTOFLEX AVC)
Glyceryl stearate and PEG 100 stearates	(ARLACEL?165)
		Polyethylene (2) stearyl ether	(BRIJ?72)
Polyethylene glycol oxide (21) stearyl ether	(BRIJ?721)
		Silica	(CAB-O-SIL)
Polyquaternium 10	(CELQUAT CS230M)
		Cetanol
The pure and mild ceteareth 20 of cetearyl alcohol	(COSMOWAX?P)
		Pure and mild two (cetyl) phosphate of cetearyl alcohol and cetanol polyethers-10 phosphate	(CRODAFOS?CES)
Cetanol polyethers-20 phosphate and cetearyl alcohol pure and mild two (cetyl) phosphate	(CRODAFOS CS-20 acid)
		The pure and mild ceteareth 20 of cetearyl alcohol	(EMULGADE?NI 1000)
Sodium silicate magnesium	(LAPONITE?XLG)
		Cetanol and octadecanol and stearyl dimethyl benzyl ammonium chloride and dimethyl stearylamine and lactic acid	(MACKADET?CBC)
Pure and mild stearamidopropyldime.hylamine of cetearyl alcohol and stearoyl amido propyl-dimethyl benzyl ammonium chloride	(MACKERNIUM is main)

The stearyl dimethyl benzyl ammonium chloride	(MACKERNIUM SDC-85)
		The pure and mild stearamidopropyldime.hylamine of cetearyl alcohol and stearoyl amido propyl-dimethyl benzyl ammonium chloride and siloxane quaternary ammonium 16	(MACKERNIUM Ultra)
The pure and mild cetostearyl alcohol glucoside of cetearyl alcohol	(MONTANOV 68EC)
		Hydroxyethylcellulose	(NATROSOL?250 HHR?CS)
Polyquaternium-37 and mineral oil and tridecanol polyethers-6	(SALCARE?SC?95)
		Polyquaternium-32 and mineral oil and tridecanol polyethers-6	(SALCARE?SC?96)
Stearic acid
		The cetyl hydroxyethylcellulose	(NATROSOL?Plus 330?CS)
Polyvinyl alcohol, PVP-K30, propane diols
		Stearic acid, behenyl alcohol, glyceryl stearate, 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)
		Polyquaternium 10	(CELQUAT?SC240C)
PAA/sodium acryloyldimethyl taurate copolymers and isohexadecane and polysorbate 80	(SIMULGEL?EG)
		Polyquaternium 44	(LUVIQUAT?Care)

[00195] other specific category of optional components comprises the alkanolamide as blowing agent and stabilizing agent; Inorganic phosphate, sulphate and carbonate as buffer; EDTA and phosphate as chelating agent; With bronsted lowry acids and bases bronsted lowry as pH value conditioning agent.

[00196] 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; And composition thereof.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.

[00197] 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.To the characteristic of acid ph value conditioning agent without limits, and can separately or be used in combination any acid ph value conditioning agent known in the art.

[00198] composition also can contain cosolvent or fining agent, for example has oxo solvent or its mixture of about at the most 4000 molecular weight polyethylene glycol, methyl propanediol, ethene, propylene or butylene.Can comprise cosolvent or fining agent as required, so that give stability and/or clarity to composition, and cosolvent or fining agent may reside in the residual film or layer of the lip-deep composition of handling.

[00199] provides the optional alkanolamide of thickening to be to composition but be not limited to: coconut oleoyl amine MEA, coconut oleoyl amine DEA, soybean grease 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 composition thereof.Alkanolamide is non-clean Surface activating agent, and if any, adds on a small quantity, thereby make the composition thickening.

E. The pH value

[00200] at 25 ℃, the pH value of bactericidal composition of the present invention 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 of this composition is approximately 2 to less than about 5, and preferably approximately 2.5 to about 4.5.

[00201] the pH value of composition should be low fully, so that at least a portion organic acid is 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, cambium or film, and withstand the flushing and be not removed, thereby lasting antiviral effect is provided.

[00202] the new and beyond thought result in order to prove that the inventive method provides has prepared following composition, measures this method control Gram-positive and Gram-negative bacteria and rhinoviral ability of control.List in percetage by weight representative in each following composition and be present in the true or actual weight amount of each component (in this method that reduces skin pH value, using) in the composition.According to those skilled in the art understood with as described below,, component prepares composition by being mixed.

[00203] in preparation of compositions and test, use following method:

[00204] a) measures quick sterilization (time limit deactivation) activity of antimicrobial product.Utilize the time limit deactivation method, measure the activity of bactericidal composition, measure the function of the survival rate of the organism that is stimulated that is exposed to the antibacterial tests composition thus as the time.In this test, under set point of temperature, the dilution aliquot sample that makes composition contacts between the time limit with known test bacterial population.At the terminal point of time period, the neutralization test composition, this has suppressed the antibacterial activity of composition.Calculate percentage or the logarithm minimizing value of primitive bacteria population.

[00205] common, the time limit deactivation method is known for those skilled in the art.

[00206] can be in subject composition under any concentration (until 100%).The selection of working concentration is the judgement according to the researcher, and those skilled in the art determine suitable concentration easily.For example, the common sample of test thickness under 50% diluting condition, and that noncohesive sample does not have is diluted.Test specimen is placed in the aseptic 250ml beaker (being equipped with magnetic stirring bar), sample volume is transferred to 100ml (if necessary) with aseptic deionized water.Carry out all tests in triplicate, the result is merged, report average logarithm minimizing value.

[00207] time of contact section selection also at one's discretion the researcher handle.Can select any time of contact of section.Typical time of contact is 15 seconds to 5 minutes scope, and is typical time of contact in 30 seconds and 1 minute.The contact temperature also can be any temperature, room temperature typically, promptly about 25 ℃.

[00208] goes up the cultivation bacterial cultures by any suitable solid culture medium (for example agar) and prepare bacterial suspension or test inoculum.Wash out bacterial population with stroke-physiological saline solution from agar then, and the population of bacterial suspension is adjusted to about 108 clump counts of every ml (cfu/ml).

[00209] following table has been listed employed in test test bacterial cultures, comprises the title of bacterium, ATCC (American Type Culture Collection) identify and the hereinafter title abbreviation of the organism of use.Staphylococcus aureus is a Gram-positive bacteria, and Escherichia coli, Friedlander and Salmonella choleraesuls are Gram-negative bacterias.

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

[00210] beaker that will contain subject composition is placed on (if expectation constant temperature) in the water-bath, or is placed on (if wanting the environmental experiment room temperature) on the magnetic stirring apparatus.Then to sample inoculation 1.0ml test bacterial suspension.The inoculum that will contain subject composition stirs 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 the decimal isarithmic scope that is diluted to then.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, counted, and calculate percentage or logarithm minimizing value for bacterium colony survivor's number.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.

[00211] use following formula to calculate logarithm minimizing value:

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

[00212] in following table, the minimizing percentage in the bacterial population is associated with logarithm minimizing value:

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

[00213] antiviral residual effect test b)

[00214] 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 ＂.

[00215] method that is used for measuring antiviral index of the present invention is to be described in improving one's methods of Sattar I (being used for the test of 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.

[00216] 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, the inoculation skin site is thoroughly purified then with the dilution of 70% ethanol/water.

[00217] method:

Test in [00218] ten minute:

[00219] the non-medicated soap washing experimenter's of initial usefulness (5 of each test products) hand, the flushing hand makes the hand drying.

[00220] use 70% Ethanol Treatment hand then, and the air drying.

[00221] test products (1.0ml) is applied to hand, except that thumb, makes the hand drying.

[00222] 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 x 10 ⁶PFU (plaque-forming unit)/ml) part is applied to each site (in the skin surface that is called as finger pad is long-pending) on hand.At this moment, by similar mode, rhinovirus solution also is applied to untreated thumb.

[00223] after dry 7-10 minute, virus is eluted each site washing 10 times with 1ml washing lotion (Earle ' s balanced salt solution (EBSS) contains 25% fetal bovine serum (FBS)+1% mould-strepto--glutamate) from each skin site.

[00224], 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 [00225] one hour:

[00226] 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 site on the finger pad, and elutes from it, fully as described in the test in top 10 minutes.

Embodiment 1

[00227] according to the present invention, by following component is mixed with the percetage by weight of indicating, till evenly, preparation can reduce the composition of surface p H value.

Component	Percetage by weight
		Citric acid	2.1
Water	In right amount

[00228] composition is applied to individual surface, skin for example, its quantity should be enough to produce the surface concentration of the about at least 10 microgram citric acids in every square centimeter of surface.After using about composition of 2 to 2.5, surface p H value is reduced to initial value from about environment value of 5 to 5.5.After using, the surface is retained to much about 5 hours under less than 3.5 pH value.The surface demonstrates good control to virus and bacterium.

Embodiment 2

[00229] this embodiment shows, has unexpected and beyond thought relation between skin pH value and rhinovirus effect.Can provide antiviral performance although previous acidic composition is applied to user's skin, especially the rhinovirus performance has been found that reducing skin pH value simply is not enough to guarantee antiviral effect.More particularly, for the effective antiviral effect of the height that obtains time expand, for example four hours, must keep the pH value of skin less than 4 in whole four hours.

[00230] in this embodiment, evaluate the rhinovirus activity after 5 minutes using organic acid soln (it has the pH value that can regulate in the certain pH value scope), to determine the effective pH value limit of composition.Preparation comprises the test solution of 1% citric acid and 1% malic acid (weight) in 10% ethanol water solvent.By adding the pH value that triethanolamine comes regulator solution, provide composition with following indicated pH value:

Composition	pH
		A	2.3
B	4.5
		C	5.6

[00231] use the interior rhinovirus finger pad test method of body to measure the rhinovirus effect of each solution.Following table has been listed subject composition, has been used testing liquid skin pH value, average log afterwards ₁₀(being applied to the virus titer inoculum of volunteer's finger) and average log ₁₀(from the virus titer of finger recovery).Testing liquid is applied to all fingers of volunteer, except the thumb.Made finger then dry 5 minutes, the rhinovirus inoculum is applied to all fingers.Thumb serves as negative control, measures inoculum by the rhinovirus titre that reclaims from thumb.In this test, two volunteers are used for the pH value of each test.The skin pH value of report is two volunteers' a mean value.

Composition	Composition pH	Skin pH	log 10(virus of inoculation)	log 10(virus of recovery)
					A	2.3	3.0	3.9	0.23
B	4.5	4.7	4.0	3.1
					C	5.6	5.6	4.1	3.6

[00232] this embodiment clearly illustrates that, 5.6 or 4.7 skin pH value is inoperative to eliminating rhinovirus, and 3.0 skin pH value can eliminate or eliminate basically rhinovirus efficiently on application on human skin.The average log rate of recovery shows that less than 1 the average virion that keeps is less than 1 virion after test, and this means that also the virus levels in the test is lower than detectability.

Embodiment 3

[00233] prepared following composition.

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

[00234] 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.

[00235] this embodiment has illustrated by the alcohol of will sterilizing and has made up the synergistic corrosion virus effect that provides with the organic acid that has less than an antiviral log P.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, has fully eliminated the test virus serotype.

Embodiment 4

[00236] prepared the following rhinovirus composition that can reduce skin pH value, and it be applied on the finger pad of human volunteer:

¹⁾Acrylate/acrylic acid C10-30 Arrcostab cross-linked copolymer

²⁾Preservative, it contains propane diols, diazonium ureine, methyl p-hydroxybenzoate and propylparaben.

The pH value of sample 2 is 3.1.

[00237] in this test, composition 2D 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.At the fixed time rhinovirus is titrated to then and attacks the I-IV group on all finger pad of each hand, thus the effect of the time that depends on of determination test composition.In the suitable time of each group, also measure 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, two hours and four hours.Average log (the rhinoviral titre of inoculation), mean skin pH value and average log (the rhinoviral titre of recovery) that following tabulation has shown the test finger pad that is obtained from the volunteer under study for action work out with group.

Group	Initial skin pH value (mean value) after using	Skin pH value (mean value) in the time of testing	Log [inoculum titre] (mean value)	Log [titre of recovery] (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

[00238] 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 four hours, and show further that eliminating fully aspect the virus attack, skin pH value is effective less than about 4.The combination of citric acid, malic acid and polymeric acid (promptly

20) can provide residual organic acid barrier layer on finger pad, this has strengthened the permanent disease-resistant cytotoxic activity of composition.

Embodiment 5

[00239] with the cleaning finger pad of following compositions-treated subjects.Before with compositions-treated, by finger pad establishment of base line skin pH value reading.On finger pad, after the drying, measure skin pH value immediately at composition, after four hours, measure once more.

Sample	Form (wt%)	Mean skin pH value (T=0)	Mean skin pH value (T=4hr)	Virus Log 10The minimizing value	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	<0.5?log 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

[00240] after handling finger pad four hours with sample A-G, 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, recover liquid nutrient medium (containing 75% EBSS and 25% FBS and 1 * antibiotic) with virus then and wash finger pad.Sample is recovered serial dilution in the liquid nutrient medium in virus, and be coated on the H1-HeLa cell, measure titre according to the plaque method.The composition (containing two mixture in citric acid, malic acid and the tartaric acid) that use contains acid obtains the complete deactivation of rhinovirus 39, promptly greater than 3 logarithm minimizing value.

Embodiment 6 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

[00241] this embodiment explanation, composition of the present invention also provides fast and broad-spectrum antibacterial activity.

Embodiment 7

[00242] with the cleaning finger pad of following compositions-treated subjects.Before with compositions-treated, by finger pad establishment of base line skin pH value reading.On finger pad, after the drying, carry out the mensuration of skin pH value immediately at composition.

[00243] 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, recover liquid nutrient medium (containing 75% EBSS and 25% FBS and 1 * antibiotic) with virus then and wash finger pad.Sample is recovered serial dilution in the liquid nutrient medium in virus, and be coated on the H1-HeLa cell according to plaque method mensuration titre.Complete deactivation with acid-containing composition acquisition rhinovirus 14 causes 4 logarithm minimizing value.

Sample	Form (wt%)	The pH value of solution value	30 seconds virus Log 10Reduce	The hand % that has virus
					A	2% citric acid, 2% malic acid, 70%ETOH, 1% polyacrylic acid	3.10	4?log	0

Embodiment 8

[00244] prepare following composition, test organic acid and organic acid mixture are for the influence of skin pH value and antiviral effect.

Sample	Form (wt%)	Mean skin pH value (T=0)	Mean skin pH value (T=2hr)	Virus Log 10Reduce
					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

[00245] the cleaning finger pad of usefulness sample A-D Processing Test object.Before with compositions-treated, by the reading of finger pad establishment of base line skin pH value.On finger pad, after the drying, measure the pH value of skin immediately at composition, after two hours, measure once more.

[00246] all samples A-D suppresses skin pH value to being lower than 4, keeps two hours.The combination 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 to skin pH value suppresses.

[00247] with latter two hour of solution-treated finger pad, with rhinovirus 39 with 1.4 * 10 ⁴The titre of pfu is applied on the finger pad.With virus on finger pad dry 10 minutes, recover liquid nutrient medium (containing 75% EBSS and 25% FBS and 1 * antibiotic) with virus then and wash finger pad.Sample is recovered serial dilution in the liquid nutrient medium in virus, and be coated on the H1-HeLa cell according to plaque method mensuration titre.Obtain the complete deactivation of rhinovirus 39, cause logarithm minimizing value greater than 3.

[00248] the following example explanation, in the presence of alcohol, polymeric acid, particularly acrylate homopolymer or copolymer are given antiviral effect.Polymeric acid have low pH value and with the good affinity of skin, As time goes on, it can keep low skin pH value effectively, and help provides lasting antiviral effect.Polymeric acid also helps the organic acid layer or the film that provide continuous basically on the processing surface, the permanent disease-resistant cytotoxic activity of enhancing composition subsequently.

[00249] in the presence of alcohol, use acrylic acid based polymer to prove for the synergistic effect that reduces skin pH value.Yet under the situation that does not have alcohol, As time goes on, acrylic acid based polymer can not keep low skin pH value to reach 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 low skin pH value (the target antiviral effect can be provided).

[00250] when being used in combination acrylic acid based polymer, also proved 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 composition thereof 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 mildness of composition by the potential stimulus that reduces composition.(rather than according to this paper) ideally, 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 9

[00251] in the aqueous solution of 70% second alcohol 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 the reading of skin pH value before handling (baseline), will point dry after mensuration immediately, after two hours, mensuration once more.Below the reading of mean skin pH value is summarized in.

[00252] beginning, extremely after about 4.5, two hours, skin pH value remains on below 5 polyacrylic acid inhibition skin pH value.The pH value (4.4) that contains the composition inhibition skin of ethanol slightly is inferior to the composition (4.5) that does not contain ethanol.This result represents when polyacrylic acid is used with ethanol, to have synergistic effect to reducing skin pH value.

[00253] in latter two hour with 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, recover liquid nutrient medium flushing finger pad with virus then.Sample is recovered serial dilution in the liquid nutrient medium in virus, and be coated on the H1-HeLa cell, measure titre according to the plaque method.Two kinds of compositions all can reduce virus titer.Yet, comparing with the composition that does not contain ethanol (reducing titre 1.5 log), the composition (reducing titre 1.8 log) that contains ethanol demonstrates bigger slightly effect at rhinovirus.

[00254] this data declaration, polyacrylic acid have suppressed 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.

[00255] for this effect is described, prepared following eight 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	Form (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

[00256] eight compositions of test are to the effect of skin pH value and viral effect.Each composition (1.8ml) is applied to thumb, forefinger and the middle finger of subjects.Before handling, measure skin pH value reading (baseline), after with product drying, measure immediately, after two hours, measure once more.

[00257] skin pH Value Data indication, polyacrylic acid and ethanol can suppress skin pH value synergistically, because in having polyacrylic composition, each composition that contains ethanol can suppress skin pH value to lower value than the composition that does not contain ethanol.Contain ethanol and polyacrylic composition and can reduce skin pH value to pH 4-5, irrelevant with the pH value of solution value.On the contrary, the composition that does not contain ethanol only suppresses skin pH value to pH 5-6, and final skin pH value is similar to the pH value of solution value.

[00258] in order to test the antiviral efficacy 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 also recovered serial dilution in the liquid nutrient medium in virus.Sample is coated on the H1-HeLa cell, and measures virus titer according to the plaque method.With the composition that contains ethanol of polyacrylic acid combination, virus titer has the logarithm minimizing value greater than 2, and the compositions display that does not contain ethanol goes out virus titer less than 1 logarithm minimizing value.Therefore, aspect reduction skin pH value, have synergistic effect between polyacrylic acid and the ethanol, this can provide bigger antiviral efficacy at rhinovirus.(rather than according to this paper) ideally, ethanol helps to provide more continuous film of organic acid or layer on skin, for example, by reducing the surface tension of composition, help composition more balanced and be administered to equably on the surface (especially skin).

Embodiment 10

[00259] prepares following composition, to further specify the antiviral effect that polyacrylic acid is provided.

Sample	Form (wt%) concentrating agents	The pH value of solution	Mean skin pH value 2hrs.	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?250 HHR?CS 2)	6.32	5.3	100％

¹⁾CRODAFOS CS20 acid is cetanol polyethers-20 and Cetyl Alcohol (Cetaryl Alcohol) and two (cetyl) phosphate; With

²⁾NATROSOL 250HHR CS is a hydroxyethylcellulose.

[00260] sample A-C (1.8ml) is applied to thumb, forefinger and the middle finger of cleaning.Before handling, after will point drying, obtain the pH value reading (baseline) of skin immediately, for sample A and B, after two hours, obtain the pH reading once more, for sample C, after four hours, obtain the pH reading once more.The mean value of skin pH value is provided in the above-mentioned table.

[00261] contain polyacrylic sample A and can reduce skin pH value to maximum degree, the pH value of final skin is pH 4.7 after two hours.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.

[00262] also tested the antiviral effect of sample A-C at rhinovirus 39.With about 10 ³The virus loads of pfu propagates on thumb, forefinger and the middle finger of each hand of handling, and dry 10 minutes.Recover liquid nutrient medium flushing finger with virus 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 antiviral effect, because find that only 63% hand is the rhinovirus positive.

Embodiment 11

[00263] embodiment 9 shows that have synergistic effect between polyacrylic acid and ethanol, this has caused the inhibition and the antiviral effect of skin pH value.Prepared following composition, with the validity of check polybasic carboxylic acid mixture and single polycarboxylic acid compositions (in each composition, having polyacrylic acid and ethanol) enantiopathy toxic effect fruit.Preferred antiviral composition contains the organic acid of the minimum number that will show that permanent disease-resistant toxic effect fruit is required.

[00264] composition is applied on the finger pad of cleaning.Shown in after the time, with about 10 ³To 10 ⁴The rhinovirus 39 of pfu is applied on hand, dry 10 minutes.Recover virus by recover liquid nutrient medium flushing hand with virus.Then sample is recovered serial dilution in the liquid nutrient medium in virus, and be coated on the H1-HeLa cell, use the plaque method to measure virus titer.Below the percentage of the hand of the rhinovirus positive is summarised in.

Form (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％

[00265] composition that contains 70% ethanol separately is not effective 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 will contain 1% citric acid and 1% malic acid and polyacrylic acid and 70% ethanol combined administration on hand the time, after four hours, do not detecting virus on hand.Littler with the single acid (4% citric acid) of polyacrylic acid and ethanol combination at rhinoviral effect, because after four hours, find that 91% hand is the rhinovirus positive.

[00266] this data show uses polyacrylic acid and ethanol to allow to use the polybasic carboxylic acid of low concentration to obtain the target antiviral effect.This improvement is at least in part owing to form organic acid residual film or layer on skin.

Embodiment 12

[00267] 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 9.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	Form (wt%)	The pH value of solution	The pH value of initial skin	4 hours skin pH value	The virus slip
						A	1% ULTREZ, 20/2% citric acid/2% malic acid/70% ethanol	3.2	2.9	3.7	>3?log 10
B	1% ULTREZ, 20/2% citric acid/2% malic acid/70% ethanol	4.34	3.4	3.7	>3?log 10
						C	1% ULTREZ, 20/2% citric acid/2% malic acid/70% ethanol	4.65	3.6	3.8	>3?log 10

[00268] composition (1.8ml) is applied to thumb, forefinger and the middle finger of cleaning.Before handling, measure the pH value reading (baseline) of skin, after will pointing drying, measure immediately, after four hours, measure once more.The mean value of above-mentioned skin pH value is drawn.

[00269] the initial skin pH value of sample skin that A-C handles is suppressed between pH 2.9 and 3.6, and wherein the pH value of solution value is low more, and initial skin pH value is low more.Yet after four hours, for all three compositions, skin pH value is approximately pH3.7.Consistent with previous embodiment, the pH value of solution does not indicate skin pH value subsequently.

[00270] also tested the antiviral effect of sample A-C at rhinovirus 39.With about 10 ³The virus loads of pfu spreads upon on thumb, forefinger and the middle finger of each hand of handling, and dry 10 minutes.Recover liquid nutrient medium flushing finger with virus 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, indicate three all sample A-C all to have antiviral effect.This improvement is at least in part owing to form organic acid residual film or layer on skin.

[00271] 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, give dermal administration pH value soft and safety, 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.

[00272] following evidence, composition of the present invention can provide continuous basically organic acid barrier layer on the processing surface.Especially, following evidence, this composition is withstood the flushing to handle surface, for example after three flushings, measures according to NMR and IR spectrum, and at least 50% non-volatile composition component (comprising organic acid) remains on the handled 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.

[00273] in the test below, the Aquo-composition (composition A) that will contain (weight) 2% malic acid, 2% citric acid, 1% polyacrylic acid, 62% ethanol and 0.5% hydroxyethylcellulose (as gelling agent) compares with the Aquo-composition (composition B) that contains 2% malic acid, 2% citric acid and 62% ethanol.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.

[00274] 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 of the composition component that keeps on handled surface reduces, and 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, detectable and non-volatile composition component effective dose remain on handle on the surface.

[00275] carries out another test, to measure water contact angle from the teeth outwards." contact angle " is the yardstick of measuring water wettability from the teeth outwards.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 does not wash	Composition A, flushing	Composition B does not wash	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

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 because the contact angle after flushing composition B the contact angle with exposed glass is identical basically.

[00276] carried out another test, with the absorption of the residual film of proof composition A to metal ion.In this test, at the film of formation composition A on glass, drying at least 4 hours is exposed in the solution with 0.5M concentration of metal ions then.Then by SEM scanning analysis sample.Data show in the table below, the film that is produced by composition A combines the metal ion of several types effectively.(rather than according to this paper) ideally, this is a kind of superficial phenomenon, because the mechanism that metal ion is transported in the film is known.

Also obtained the reflection microphoto that shows the surface coverage of composition A and B.Appended microphoto 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.Appended microphoto is the digital translation of reflected value, and it provides the directly related property with surface coverage.Microphoto proves that B compares with composition, and composition A provides has the film that the adhesiveness, dispersiveness and the crystal that have improved form.

Embodiment 13

[00277] other bacterium and fungi are carried out the time limit inactivation test, with the wide spectrum effect of the proof present composition.In this test, tested following bactericidal composition.

Component	Percetage by weight
		Cetanol	1.00
Glycerine	1.00
		Isopropyl palmitate	1.00
Dimeticone 100 CST	1.02
		Ethanol SDA-40B	3.09
Natrosol 250 HHX	0.26
		Deionized water	10.94
Deionized water	17.65
		ULTREZ 10 polymer	1.01
Ethanol SDA-40B	58.82
		Citric acid	2.00
Malic acid	2.00
		Sodium hydroxide 50%	0.22

[00278] 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 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 ℃, continue 48 ± 4 hours (for aurococcus, Escherichia coli, listeria monocytogenes) 30 ± 2 ℃, continue 48 ± 4 hours (for enterobacter cloacae) 26 ± 2 ℃, continue 72 ± 4 hours (for Candida albicans)

[00279] 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 rate (CFU/mL)	Average survival rate (CFU/mL)	Logarithm minimizing value	Reduce percentage
					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 rate (CFU/mL)	Average survival rate (CFU/mL)	Logarithm minimizing value	Reduce percentage
					15	2?x?10 2，<100	<1.5?x?10 2	>5.08	>99.999
30	<100，<100	<100	>5.26	>99.999

Listerisa monocytogenes in mjme ATCC 7644

Time of contact (second)	Survival rate (CFU/mL)	Average survival rate (CFU/mL)	Logarithm minimizing value	Reduce percentage
					15	<100，3?x?10 2	<2.0?x?10 2	>5.15	>99.999
30	<100，<100	<100	>5.45	>99.999

Enterobacter cloacae ATCC 13027

Time of contact (second)	Survival rate (CFU/mL)	Average survival rate (CFU/mL)	Logarithm minimizing value	Reduce percentage
					15	＜100, pollute	<100	>5.52	>99.999
30	5?x?10 2，6?x?10 2	5.5?x?10 2	4.78	>99.998

Candida albicans ATCC 10231

Time of contact (second)	Survival rate (CFU/mL)	Average survival rate (CFU/mL)	Logarithm minimizing value	Reduce percentage
					15	<100， <100	<100	>4.40	>99.996
30	<100， <100	<100	>4.40	>99.996

[00280] these data show, 15 and 30 seconds time of contact, the present composition demonstrated about 4 to 5 logarithm minimizing value at staphylococcus aureus ATCC 6538, Escherichia coli ATCC 11229, monocyte Listeria monocytogenes ATCC 7644, enterobacter cloacae ATCC 13047 and Candida albicans ATCC10231.

[00281] data show above, contain this bactericidal composition of organic acid and also can control fungi effectively, 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 former activity at fungi.Yet Mycotoruloides comprises many species, and the test Candida albicans is because it can cause candidiasis continually.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 bactericidal composition, has shown at least 4 logarithm minimizing value.

Embodiment 14-17

[00282] following is other example that is effective to the composition of this method.

	Embodiment 14	Embodiment 15	Embodiment 16	Embodiment 17
					Ethanol SDA-40B 190 checks	75	85	95	25
Sad		0.05		0.05
					Citric acid	0.5	0.5	1.5	0.5
Malic acid	0.5	0.5	1.5	0.5
					Pluronic?F108		0.2	0.2	0.2
Sodium hydroxide or buffer solution	qs	qs	qs	qs
					Deionized water	24	13.75	1.8	73.75
					Add up to	100	100	100	100

[00283] all compositions of embodiment 14-17 are cleanings and colourless, keep small residue in the time of on being sprayed on counter top, make its drying.

Product form

[00284] can be formulated as various product forms with compound or composition antiviral effect with reducing surface p H value and providing antibiotic, comprise liquid, gel, semisolid and solid.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, design in order to utilize sticky assignment device or utilization finger.The solid product form can be powder, thin slice, particle, tablet, spherolite, lozenge, ball, agglomerate, piece material, solid block, unit dose or similar solid product form known in the art.This bactericidal composition can be prepared into the composition of diluted for use, or be prepared into the concentrate of dilution before using.

[00285] a kind of specific product form is the liquid or solid composition that is configured in the water solubility packing.Packing is joined in the water of normal quantity, when the packing dissolving, discharge composition.The packing of water solubility typically comprises polyvinyl alcohol.The form of a kind of water solubility packing is disclosed in U.S. Pat 5,316, and in 688, this paper is introduced into as a reference.Many other water solubility packings 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.

[00286] another kind of useful product form is the stable solid block that can be added to the water, thereby the fluid composition of putting into practice this method is provided.Described can be tablet, agglomerate, ball or big solid block, and for example, the weight of piece can be from less than one ounce to several pounds, and this depends on final use.This comprises cementing agent usually.A kind of stable body is disclosed in U.S. Pat 6,432, and in 906, this paper is introduced into as a reference.

[00287] another product form is that reactive compound or composition are incorporated into absorbent or absorption carrier, for example in polymer particle or the inorganic particle.Can ortho states load carrier that use or that be incorporated in the other products form be liquid, gel, semisolid or solid.

[00288] 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.

[00289] another kind of product form is the article that contain reactive compound or composition, and for example latex glove can be applied to reactive compound or composition or embed in the article.During use, 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.

The surface of handling

[00290] just as discussed above, can handle animate and inanimate surface according to the inventive method.The surface that is even more important is warm blooded animal skin, particularly application on human skin, thereby makes bacterium and virally inactivated and block its propagation.Yet this method also can be effective to handle all types of other life surface and abiotic surface.

[00291] for example, this compound or composition can be applied to food, for example meat, bird, seafood, fruit and vegetables.Composition is applied to food surface with controlling microbial.The example of microorganism comprises the pathogenic microorganisms (for example listerisa monocytogenes in mjme, enterohemorrhagic Escherichia coli, salmonella or the like) that can cause disease and the corrupt mushroom that can influence taste, color and/or the smell of ultimate food (for example pseudomonas, acinetobacter, Moraxella, alcaligenes, Flavobacterium, Erwinia, or the like).

[00292] composition can be applied to any food that the human or animal consumes, comprise Food ﹠ Drink, specifically, meat, bird, seafood, fruit and vegetables.Some non-limitative examples of meat products comprise muscle or its any part of any animal, comprise beef, pork, veal, buffalo meat and lamb meat.Some non-limitative examples of seafood comprise scallop, shrimp, crab, octopus, shellfish, squid and lobster.Some non-limitative examples of bird comprise big chick, turkey, ostrich, chicken, squab, guinea fowl, pheasant, duck, goose and emu.Some non-limitative examples of fruit and vegetables comprise cedra fruits, tree fruit, tropical fruit (tree), berry, lettuce, green soya bean, pea, carrot, tomato, mushroom, potato, root vegetables, dish bud, seed, nut, animal feed, and cereal for example corn, wheat and oat.

[00293] can composition be applied to food surface with some modes, comprise composition spraying, spraying, spreading and foamed to food, or in composition infusion of food.Can use composition by injection, for example use injection solution, or can use composition to be applied to the marinade on the food or the form of emollient component.Composition use can with physical agitation, for example air spraying, friction or brush combination.Using of composition can be manually to use, or can use composition 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.Said composition can be used once on food, abandon then, or said composition can be recovered utilization.

[00294] food can also be impregnated in the container that contains composition.Preferably stir composition, the speed of killing the microorganism that is attached to food with the effect that improves this solution and solution.

[00295] in another embodiment of the invention, can handle food with the form of foam of composition.When in use, can prepare foam by lathering surfactant is mixed with composition.In nature, foaming surfactant can be nonionic, anionic or cationic.

[00296] in another embodiment of the invention, can be with the compositions-treated food of thickening or gelation.Under thickening or gel state, composition can keep contacting of long period with food, improves antibacterial effect thus.The composition of thickening or gelation also can adhere to vertical surface.

[00297] with regard to the antibacterial effect of composition, the consumption of the composition of every pound of food is an important parameters.For sheet/base of handling bird, fish, fruit and vegetables and red meat, in dipping and spraying method, the preferable amount of composition be about 0.5oz/lb food to about 3.0oz/lb food, and more preferably about 1.0 to about 2.0oz/lb food.For the ox bone frame, preferable amount be every beef about 0.5 to about 2.5 gallons, and more preferably about 1.0 to about 2.0 gallons/face.

[00298] handles food with sanitizing composition and be described in greater detail in U.S. Pat 5,389,390,5,409,713,6,063,425,6,183,807,6,113,963,6, in 514,556 and 6,545,047, whole disclosures that this paper introduces them as a reference.

[00299] also composition can be applied to animal alive, for example flood nipple or handle hoof.The dipping nipple is considered to reduce the method for dairy cow mastitis.Mastitis is one of face the most common of dairy and expensive economically disease.Economic loss is the milk quality of difference, the result who hangs down milk yield and may pick out long-term infection animal.Have been found that and before and after milking, use bactericidal composition can prevent mastitis like a bomb.When composition was used to the nipple dipping, desirable was that adding can increase composition effect or other component of other benefit is provided, and for example shows the dyestuff that composition has correctly been used.

[00300] composition also can be handled as lavipeditum or hoof, with prophylactic propagation.For example, can prepare and use composition, so that the farm labourers walks by composition, prophylaxis of microbial is propagated on their boots thus.Perhaps, can use composition by the mode of composition, the propagation of prophylaxis of microbial thus, and the chance that any infection on the treatment animal hooves is provided with animal walking.

[00301] this method also can be used for handling inanimate surfaces, comprises soft-surface and crust.Term used herein " hard " is meant the surface that comprises the infusibility material, for example glaze and unglazed tile surface, brick, porcelain, pottery, metal, glass, or the like, and comprise timber and duroplasts, for example bakelite, polystyrene, vinyl, acrylic compounds, polyester, or the like.Crust can be a porous or imporous.Methods for disinfecting hard surfaces 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.

[00302] this method can be used for handling the crust in following: processing factory (for example dairy, wine brewing and food processing factory), health-care facilities (for example hospital, clinic, Surgicenter, dental clinic and laboratory), long-term care facility (for example nursing the chamber), farm, pleasure-boat, hotel, aircraft, school and private residence.

[00303] this method can be used for the processing environment crust, 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, dental tool and instrument, and the equipment that is used for healthcare industry and public kitchen, for example, meat block slicing machine, chopping block, cutter, fork, spoon, vessel (for example basin, jar and dish), cutting equipment, or the like.

[00304] treatable inanimate surfaces is including, but not limited to the surface of contact environment, for example table, floor, wall, kitchen utensils (comprising basin, jar, cutter, fork, spoon, dish), food cooking and making surface comprise dish and food equipment, storage tank, drum, pipeline, pump, flexible pipe and other process equipment.A kind of effective application of composition is a dairy equipment, and it 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.

[00305] 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 composition spraying, wiping, foamed, spraying, brushing, liner be coated with stain, spreading and be atomised to life or inanimate surfaces on.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-fiber mat material, 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.

[00306] 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.

[00307] method of the present invention can be used to handle medical dolly, medical shrouding and other Medical Instruments, device and equipment effectively.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 used for handling utensil and the chair that is present in barber shop and hair and nail salon institute effectively.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.

[00308] except crust, this method also can be used for handling soft inanimate surfaces, for example textile, for example clothes, 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.

[00309] for example use cleanser/hand, operation abrasive cleaner, body sprays, bactericide, disinfectant, hand with sanitizer, deodorant and similar personal care product, can put into practice method of the present invention.Other type of composition that can use in the method comprises Efferescent compositions, for example emulsifiable paste, mousse or the like, and comprise organic and composition inorganic filler, and for example emulsion, lotion, emulsifiable paste, ointment, ointment, or the like.Provide the wiping article by suitable combination thing or composition being incorporated into clean in thing or the fabric, also can hands-on approach.The wiping article can be used for controlling the microorganism on life or the inanimate surfaces.

[00310] in one embodiment of the invention, the personnel that suffer from the rhinovirus flu maybe may contact other individual personnel that suffer from the rhinovirus flu, can be applied to compound or the composition that skin pH value is reduced to less than 4 on hand his or her.But thisly use kill bacteria and make the rhinovirus particle inactivation that is present on hand.Compound of using or composition (both can rinsing out or be retained on hand) can provide lasting antiviral activity.Therefore, the rhinovirus particle can not propagated the individuality that infects to not by hand adversary circulation way.The amount that compound or composition are used, frequency of administration and operating period will change according to needed sterilisation level, for example the contamination by micro degree.

[00311] in short time of contact, this method can provide the benefit of killing Gram-positive and Gram-negative bacteria and the control of wide spectrum virus of wide spectrum.In short contacting time, cause bacterium in fact logarithm minimizing value be important, this is because the time range that is used for cleaning and disinfection life and inanimate surfaces 15 to 60 seconds typically.This method also can be given lasting antiviral activity to contact surface, and this raising is owing to can be retained in the residual barrier layer or the film of lip-deep composition component after the volatile component evaporation of composition.

[00312] 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 (71)

1. virus on the control inanimate surfaces and the method for bacterium comprise making described surface and the pH value of inanimate surfaces can being reduced to less than about 4 and keeping about at least 0.5 hour compound or composition to contact.

2. the process of claim 1 wherein that described compound or composition are reduced to the pH value of inanimate surfaces less than about 4, and kept about at least two hours.

3. the process of claim 1 wherein that described compound or composition are reduced to the pH value of inanimate surfaces less than about 4, and be retained to much about eight hours.

4. the process of claim 1 wherein that described compound or composition can be reduced to the pH value of inanimate surfaces less than about 3.5.

5. the process of claim 1 wherein that described compound or composition can be reduced to the pH value of inanimate surfaces less than about 3.

6. the process of claim 1 wherein that described compound or composition are allowed to be retained on the inanimate surfaces.

7. the process of claim 1 wherein described compound or composition are rinsed out from abiotic surface.

8. the method for claim 1, the wherein said compound that can reduce the pH value of inanimate surfaces is selected from following: (a) organic acid, (b) inorganic acid, (c) mineral salt, it comprises and has valent cation of 2,3 or 4 and the pH value of skin can be reduced to counter ion less than about 4, (d) complex compound of aluminium, zirconium or aluminum-zirconium and (e) its mixture.

9. the method for claim 8, wherein said compound forms the organic acid barrier layer on inanimate surfaces.

10. the method for claim 9 wherein forms the continuous basically layer of described compound on inanimate surfaces.

11. the process of claim 1 wherein that the compound of the described pH value that can reduce inanimate surfaces is present in the composition with about 0.05% to about 15% the quantity that accounts for described composition weight.

12. the method for claim 8, wherein the organic acid in described composition has the log P less than 1.

13. the method for claim 8, wherein the organic acid in described composition has 1 or bigger log P.

14. the method for claim 8, wherein said organic acid comprise and have less than first organic acid of 1 log P and have 1 or second organic acid of bigger log P.

15. the method for claim 8, wherein said organic acid comprise monocarboxylic acid, polybasic carboxylic acid, have a plurality of carboxyls, polymeric acid, its acid anhydrides or its mixture of phosphate radical, sulfonate radical and/or sulfate radical part.

16. comprising, the method for claim 8, wherein said organic acid have structure RCO ₂The monocarboxylic acid of H, wherein R is C _1-10Alkyl, hydroxyl C _1-6Alkyl, halogen C _1-6The phenyl of alkyl, phenyl or replacement.

17. the method for claim 16, wherein said monocarboxylic acid be selected from acetate, propionic acid, sad, glycolic, lactic acid, benzoic acid, phenylacetic acid, phenoxyacetic acid, neat graceful acid, 2-, 3-or 4-hydroxybenzoic acid, the acid of N-anilide, neighbour, or rubigan acetate, neighbour, or parachlorophen-oxyacetic acid and composition thereof.

18. the method for claim 15, wherein said polybasic carboxylic acid comprise two to four carboxyls, and randomly comprise one or more hydroxyls, amino or both.

19. the method for claim 18, wherein said 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 composition thereof.

20. the method for claim 15, wherein said polybasic carboxylic acid comprises the acid anhydrides of polybasic carboxylic acid.

21. the method for claim 15, wherein said polymeric acid have about 500 to about 10,000, the molecular weight of 000g/mol.

22. the method for claim 15, wherein said polymeric acid be water-soluble or water dispersible.

23. the method for claim 15, wherein said polymeric acid are selected from polymerization of carboxylic acid, polymerization sulfonic acid, Sulfated polymer, polymer phosphate and composition thereof.

24. the method for claim 15, wherein said polymeric acid can form firm film on abiotic surface.

25. the method for claim 15, wherein said polymeric acid comprises acrylic acid homopolymers or copolymer.

26. the method for claim 8, wherein said organic acid comprises polybasic carboxylic acid and polymerization of carboxylic acid.

27. the method for claim 26, wherein said polybasic carboxylic acid comprise citric acid, malic acid, tartaric acid or its mixture, described polymerization of carboxylic acid comprises the homopolymers or the copolymer of acrylic or methacrylic acid.

28. the process of claim 1 wherein that described composition further comprises gelling agent.

29. the process of claim 1 wherein that described composition has about 2 to less than about 5 pH value.

30. the method for claim 8, wherein said inorganic acid is selected from phosphorous acid, phosphoric acid, pyrophosphoric acid, polyphosphoric acid and composition thereof.

31. comprising, the method for claim 8, wherein said mineral salt be selected from following cation: magnesium, calcium, barium, aluminium, iron, cobalt, nickel, copper, zinc, zirconium and tin.

32. the method for claim 31, wherein said counter ion are selected from bisulfate ion, sulfate radical, dihydrogen phosphate, phosphoric acid one hydrogen root, chlorion, iodide ion, bromide ion and nitrate anion.

33. the method for claim 32, the counter ion of wherein said mineral salt comprises chlorion.

34. the method for claim 8, wherein said mineral salt comprise divalent zinc salt.

35. the method for claim 8, wherein the complex compound of aluminium, zirconium or aluminum-zirconium comprises the complex compound of aluminium.

36. the method for claim 1, wherein said composition further comprises 0.1% to about 5% antibacterial agent, and this antibacterial agent is selected from phenol antibacterial agent, quaternary ammonium antibacterial agent, N-anilide, biguanides, phenmethylol, benzoyl peroxide, hydrogen peroxide and composition thereof.

37. comprising, the method for claim 36, wherein said antibacterial agent be selected from following phenol antibacterial agent:

(a) has the 2-xenol compound 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 biphenol compound of following array structure:

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

(d) its mixture.

38. the method for claim 36, wherein said antibacterial agent comprise the quaternary ammonium antibacterial agent with following array structure:

R wherein ₁₁Be alkyl, aryl or the alkaryl substituting group that comprises 6 to 26 carbon atoms, R ₁₂, R ₁₃And R ₁₄Be to comprise the substituting group that is no more than 12 carbon atoms independently, X is the anion that is selected from halogen, methylsulfate, ethyl sulphate and p-toluenesulfonyl, or

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, ethyl sulphate or p-methyl benzenesulfonic acid root.

Be selected from following N-anilide or biguanides 39. the method for claim 36, wherein said antibacterial agent comprise: neko, diphenylurea, salicylamide, Tribromsalan, tetrachloro are for salicylamide, Flusalan, chlorhexidine gluconate, chlorhexidine hydrochloride and composition thereof.

40. the process of claim 1 wherein that described composition further comprises sterilization alcohol, its quantity accounts for 10% to about 90% of composition weight.

41. the method for claim 40, wherein said sterilization alcohol comprises one or more C1-6 alcohol.

42. the process of claim 1 wherein that described composition further comprises the polyhydroxyl solvents of about at the most 30% weight, this polyhydroxyl solvents is selected from glycol, triol and composition thereof.

43. the process of claim 1 wherein that described composition further comprises the hydrotropic agent of about at the most 30% weight.

44. the process of claim 1 wherein that described composition further comprises about 0.1% gelling agent to about 5% weight.

45. the method for claim 44, wherein said gelling agent comprise natural gum, synthetic polymer, clay, oil, paraffin or its mixture.

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

47. the method for claim 46, wherein said surfactant comprise surfactant or its mixture of anionic, cationic, nonionic or both sexes.

48. the process of claim 1 wherein that according to the mensuration of carrying out at aurococcus, inanimate surfaces has at least 2 logarithm minimizing value at Gram-positive bacteria after contacting for 30 seconds.

49. the process of claim 1 wherein that according to the mensuration of carrying out at Escherichia coli, inanimate surfaces has at least 2.5 logarithm minimizing value at Gram-negative bacteria after contacting for 30 seconds.

50. the process of claim 1 wherein that inanimate surfaces has at least 4 logarithm minimizing value at nonenveloped virus after contacting for 30 seconds.

51. the process of claim 1 wherein and make rhinovirus, picornavirus, adenovirus, rotavirus, influenza virus, herpes virus, Respiratory Syncytial Virus(RSV), coronavirus, enterovirus and similar pathogenic virus inactivation.

52. the process of claim 1 wherein and before described surface is exposed to virus, use composition.

53. the process of claim 1 wherein and within the time period of twenty four hours, repeatedly use composition.

54. the method for claim 8, wherein after water flushing ten times, the compound of effective dose is retained on the barrier layer of inanimate surfaces.

55. the method for claim 8, wherein after water flushing three times, at least 50% weight of the non-volatile component of composition is present on the inanimate surfaces.

56. the method for claim 1 further comprises the step that rinses out composition from inanimate surfaces.

57. the process of claim 1 wherein to contact 5 hours afterwards with compound or composition, inanimate surfaces has at least 3 logarithm minimizing value at the unsettled virus of acid.

58. the method for claim 57, the unsettled virus of wherein said acid comprises rhinovirus serotype.

59. the method for claim 50, wherein said virus comprises rotavirus serotype.

60. the method for claim 50, wherein said virus comprises influenza virus.

61. the process of claim 1 wherein to contact 8 hours afterwards with compound or composition, inanimate surfaces has at least 2 logarithm minimizing value at the unsettled virus of acid.

62. the process of claim 1 wherein that described compound or composition further control the fungi on the inanimate surfaces.

63. the method for claim 62, wherein said fungi comprise mould, saccharomycete or both.

64. the method for claim 63, wherein said fungi comprises saccharomycete.

65. the method for claim 64, wherein said saccharomycete comprises Candida albicans.

66. the method for claim 62, wherein handled inanimate surfaces are exposed to described composition after 15 seconds, described composition is given at least 4 logarithm minimizing value at the Candida albicans on the handled inanimate surfaces.

67. the process of claim 1 wherein that with the described compound administration that can reduce inanimate surfaces pH value in inanimate surfaces, its quantity is every square centimeter of inanimate surfaces at least 10 microgram compounds.

68. the process of claim 1 wherein that described inanimate surfaces is a crust.

69. the method for claim 68, wherein said crust is a food contacting surface.

70. the process of claim 1 wherein that described food contacting surface is arranged in food processing factory, kitchen or restaurant.

71. the process of claim 1 wherein that described inanimate surfaces is a pressure release surface.

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