CN1265028A

CN1265028A - Mild, leave-on antimicrobial compsns.

Info

Publication number: CN1265028A
Application number: CN98807631A
Authority: CN
Inventors: P·W·彼尔斯; J·M·摩根; K·G·拜尔; W·岑; T·A·拜肯; M·L·克莱普; R·瓦尔仑
Original assignee: Procter and Gamble Co
Current assignee: Procter and Gamble Co
Priority date: 1997-06-04
Filing date: 1998-05-29
Publication date: 2000-08-30
Also published as: AU745392B2; CA2291249A1; WO1998055081A2; CA2291249C; AR012240A1; WO1998055081A3; CO4940379A1; AU7704898A; JP2001518941A; BR9811706A; PE79499A1; EP0996420A2

Abstract

The present invention relates to a leave-on antimicrobial composition characterized in that it comprises from 0.001 % to 5 % of an antimicrobial active; from 0.05 % to 10 % of an anionic surfactant; from 0.1 % to 10 % of a proton donating agent; and from 0 % to 99.85 % of water; wherein the composition is adjusted to a pH of from 3.0 to 6.0; wherein the leave-on antimicrobial composition has a Gram Positive Residual Effectiveness Index of greater than 0.5; and wherein the leave-on antimicrobial composition has a Mildness Index of greater than 0.3. The present invention also relates to a leave-on antimicrobial cleansing composition which has a Gram Positive Residual Effectiveness Index of greater than 0.5. It also relates to a leave-on antimicrobial cleansing composition which has a One-wash Immediate Germ Reduction Index of greater than 1.0. The invention also encompasses methods for cleansing skin and providing residual effectiveness versus Gram positive bacteria using these products.

Description

Gentle leave-on antimicrobial compositons

Technical field

The present invention relates to retention type topical anti-microbial compositions, when being administered to it on skin, said composition can provide the antimicrobial efficacy of reinforcement.Especially, when comparing with prior art combinations, leave-on antimicrobial compositons of the present invention provides the time-delay effect of unforeseen in the past anti-temporary gram negative bacteria, also reduces the effect of pathogenic bacteria on the skin before providing when the time-delay effect of unforeseen resisting gram-positive bacteria and improved use immediately.

Background technology

Human health can be subjected to the influence of multiple microorganism entity.Virus and infecting of antibacterial can cause multiple disease.Medium have improved the understanding of the public to microorganism problem to the concern of situations such as alimentary toxicosis, streptococcal infection.

Known employing antimicrobial or non-medicine soap clean crust, food (for example fruit or vegetable) and skin (particularly hands) can remove multiple virus and antibacterial from the surface that is cleaned.The removal of virus and antibacterial is to be reached by the surface activity effect of soap and the mechanism of washing process.Therefore, known and suggestion people often reduce virus and the propagation of antibacterial by cleaning.

Find that the antibacterial on the skin can be divided into two classes: that retain and temporary antibacterial.Retaining antibacterial is gram positive bacteria, and it can form fixedly bacterium colony at the surface and the outermost layer of skin, to preventing the living important and useful effect that has of moving of other more deleterious antibacterial and fungus.

Temporary antibacterial does not belong on the skin the conventional bacterium colony that retains, but can be deposited on the skin when airborne pollutant touch on the skin or keep in antibacterial when pollutant contact with skin generation physics.Temporary antibacterial generally is divided into two groups: gram positive bacteria and gram negative bacteria.Gram positive bacteria comprises that pathogen is as staphylococcus aureus, streptococcus pyogenes and Clostridium botulinum.Gram negative bacteria comprises pathogen, as Salmonella, escherichia coli, Klebsiella pneumoniae, haemophilus, bacillus pyocyaneus, Bacillus proteus and shigella dysenteriae.The difference of gram negative bacteria and gram positive bacteria generally is additional protection sexual cell film, and like this, gram negative bacteria generally is not subject to the influence of topical anti-microbial activating agent.

The antibiotic cleaning product certain hour that gone on the market in a variety of forms.Its form comprises antibacterial soap, hard surface cleaner and surgery disinfectant.That is prepared floats the type antimicrobial soap can remove antibacterial in washing process.The liquid antimicrobial cleansing agent sees US4847072 (people such as Bissett, 1989.7.11 authorize), 4939284 (Degenhardt, 1990.7.3 authorizes) and 4820698 (Degenhardt, 1989.4.11 authorize), all the elements all be combined in the present invention this as a reference.At last, developed the cleaning course that these traditional antimicrobial soap are used to have water.This is that the occasion of water is being arranged with regard to the use that has limited them.

Some traditional product particularly the retention type water preparation of hard surface cleaner, surgery disinfectant and some alcohol radicals (as Purell ^) in adopted high-load alcohol and/or potent surfactant, this can make the skin histology mummification and produce stimulate.Ideal personal cleanser is cleaning skin leniently, does not have or do not have substantially zest, and frequent the use can not make the excessive mummification of skin yet, preferably tackles skin and has the effect of moistening.

The retention type is local to be used for humidification skin and many other purposes in the past with water preparation, foam and gel.But these retention type compositionss provide minimum antimicrobial efficacy.

The PCT application WO 92/18100 that is disclosed in the people such as Keegan on October 29th, 1992 applies for having proposed the liquid skin cleaning agent among the WO 95/32705 with the PCT that is disclosed in 7 days people such as Fujiwara of nineteen ninety-five December, this cleaning agent comprises the acid compound of gentle surfactant, antibacterial and buffering pH value, and it can provide improved antibiotic property.But here acid compound only is used to regulate pH value, and Zhi Bei compositions can not carry required non-dissociated acid so that good antimicrobial efficacy to be provided like this.This situation that comprises in the invention of Keegan and Fujiwara is the preferred gentle surfactant that uses, and comprises non-ionic surface active agent.Keegan and Fujiwara do not point out to use their compositions, for example retention type water preparation under anhydrous situation.

US3141821 (Compeau, 1964.7.21 authorize), and Ciba-Giegy, Inc. has proposed anion surfactant, anti-microbial active and acid are used for skin antibacterium Cleasing compositions about the technical literature of the Irgasan DP 300 (triclosan Triclosan ) of " basic formulations 89/42/01 that is used for hand disinfection ".But the high active surfactant of selecting for use can make this retention type compositions produce xerosis cutis and stimulation.And these documents are not all pointed out to use antimicrobial compositions, for example retention type water preparation with anhydrous form.

Gram negative bacteria such as Salmonella, escherichia coli and shigella, and gram positive bacteria such as staphylococcus aureus, streptococcus pyogenes and Clostridium botulinum can be unhealthful, need badly preparation have improved to temporary gram negative bacteria or improved to that retain and temporary gram positive bacteria the time-delay antibacterial action or can when using, improve and remove the pathogenic bacteria effect and immediately the skin gentleness and the retention type part antimicrobial compositions that can under anhydrous condition, use.Existing product can not have these advantages concurrently.

The applicant finds: with known antimicrobial acivity composition with as to the specific organic and/or mineral acid of proton reagent and the specific shared retention type topical anti-microbial compositions that makes of anion surfactant with this mildness and antimicrobial efficacy, more than each component all be deposited on the skin.Sedimentary active component combination of can and select for proton reagent and anion surfactant makes it have the antibacterial action of new height with contact skin the time.

The invention summary

The present invention relates to leave-on antimicrobial compositons, it is characterized in that wherein containing 0.001-5% antimicrobial acivity composition; The 0.05-10% anion surfactant; 0.1-10% gives proton reagent; With 0-99.85% water; Wherein the pH regulator of compositions is to 3.0-6.0; Wherein the gram negative bacteria of leave-on antimicrobial compositons time-delay antibiotic effect index is greater than 0.3; The mildness index is greater than 0.3.

The invention still further relates to gram positive bacteria time-delay antibiotic effect index greater than 0.5 retention type antimicrobial cleansing compositions.Also relate to and once clean instant bactericidal index greater than 1.0 retention type antimicrobial cleansing compositions.

The invention still further relates to and adopt leave-on antimicrobial compositons of the present invention to reduce the method that temporary gram positive bacteria is propagated.

Detailed Description Of The Invention

Leave-on antimicrobial compositons of the present invention is providing aspect the anti-gram negative bacteria time-delay effect, anti-temporary gram positive bacteria time-delay effect aspect or to reduce on the skin pathogenic bacteria quantitative aspects all very effective, and to the skin gentleness.

Here the term of Cai Yonging " leave-on antimicrobial compositons " is meant and is fit to be administered on the application on human skin to suppress the product that temporary pathogenic bacteria grows and survives on the skin.

After date can suppress the growth of antibacterial on the surface when term " time-delay antibiotic effect " was meant behind washing/rinse cycle one section.

Compositions of the present invention also is applicable to the processing of acne.Term used herein " acne treatment " is meant prevention, stops and/or suppresses acne formation on the mammal skin.

Compositions of the present invention is used for also can having basic instant (that is, emergent) improvement to skin appearance behind the skin.More specifically say, the present composition also is applicable to adjusts skin matter, comprises and adjusts visible on skin and/or tactile discontinuity, comprises vision and/or tactile discontinuity on skin texture and/or the color, particularly relevant discontinuity with skin aging, but be not limited only to this.This discontinuity may or cause by inside and/or external factor initiation.External factor comprises ultraviolet radiation (for example sun exposure), environmental pollution, wind, high temperature, low humidity, potent surfactant, abrasive material etc.Internal factor comprises that chronic biochemistry aging and other skin inside changes.

Adjustment skin matter comprises the preventing and/or treating property adjustment to skin matter.Here said preventative adjustment skin matter comprises and delays, reduces and/or prevent vision and/or tactile discontinuity.Here said therapeutic is adjusted skin matter and is comprised: improve and for example reduce, reduce and/or eliminate these discontinuities.Adjust skin matter and comprise and improve skin appearance and texture, for example make skin more smooth, evenly and/or texture better.Here said adjustment skin matter comprises the adjustment aging character." adjust skin aging feature " comprises that preventative adjustment and/or therapeutic adjust one or more these category features (promptly adjust the signal of skin aging, for example microgroove, wrinkle or pore comprise that preventative adjustment and/or therapeutic adjust these features).

" skin aging feature " comprises the performance that all are outside visible and can touch, and other macroscopic view or microcosmic effect that is caused by skin aging, but is not limited only to this.These features may be caused or caused by inside or external factor (for example chronic aging and/or environmental nuisance).This feature may be caused by the evolution of following structure discontinuity, as wrinkle, comprise appearance microgroove and thick dark stricture of vagina, the skin lines, the crack, lump, big pore is (for example with sweat duct, accessory structure such as sebaceous gland or hair follicle is relevant), peeling, the skin of decortication and/or other form is inhomogeneous or coarse, skin lack flexibility (functional skin elasticity loss of proteins and/or inactivation), sagging (comprising ocular and lower jaw edema), lax, the skin loss in toughness, skin recovery loss to distortion, variable color (comprising eyelet down), form speckle, xanthoderma, skin part hyperpigmentation such as senile plaque and freckle, keratinization, unusual differentiation, hyperkeratosis, elastosis, collagen destroys, and other is at horny layer, corium, epidermis, the tissue that occurs in particularly adjacent with the skin tissue of skin heart system (for example blood capillary) and subcutaneous tissue changes, but is not limited only to this.

Unless otherwise indicated, all percentage ratios and ratio all by weight, and unless otherwise indicated, it is all measured under 25 ℃.The present invention can comprise following neccessary composition and other described optional member, or by or form by them substantially.1. composition

Leave-on antimicrobial compositons of the present invention contains antimicrobial acivity composition, anion surfactant and gives proton reagent.These components are selected, thereby made the present composition satisfy the following effect and the requirement of mildness.Need be to each components selection on other components selection is decided.For example, if select the weak acid conduct to give proton reagent, be the effect of realization compositions,, necessary surfactant and/or interior high-load acid of prescribed limit and/or the specific effective active composition that adopts higher biological activity (but the possibility mildness reduces).Equally, when not having the surfactant of effect, then must adopt stronger acid and/or high-load acid for the effect that realizes compositions if employing is gentle.If adopt potent surfactant, then should adopt mildness reagent.As follows to each components selection standard: A. antimicrobial acivity composition

Contain in the leave-on antimicrobial compositons of the present invention and account for compositions 0.001-5% (weight), preferred 0.05-1% (weight), more preferably 0.05-0.5% (weight), the more preferably antimicrobial acivity composition of 0.1-0.25% (weight).The definite consumption of antimicrobial composition will be decided on concrete active component in the compositions, because the different activities composition has different effectiveness intensity.For avoiding interacting, should adopt the non-cationic active component with anion surfactant of the present invention.

Classify the example that is applicable to non-cationic antimicrobial reagent of the present invention down as:

Pyrithione, particularly Zn complex (ZPT)

Octopirox (Octopirox )

Dimethylformamide dimethyl base alcohol allantoin (Glydant )

Methylchloroisothiazandnone/Methylisothiazolinone (Kathon CG )

Sodium sulfite

Sodium sulfite imidazolidinyl urea (Germall 115 ) diazacyclo pentyl urea (Germall II ) benzylalcohol 2-bromo-2-nitropropane-1,3-glycol (Bronopol ) formalin (formaldehyde) iodopropylene base butyl carbamate (Polyphase P100 ) chloroacetamide Methanamide methyl dibromo nitrile glutaronitrile (1,2-two bromo-2,4-dicyanobutane or Tektamer ) glutaraldehyde 5-bromo-5-nitro-1,3-diox (Bronidox ) phenethanol neighbour-phenyl phenol/neighbour-phenyl phenol sodium sodium hydroxy methyl glycinate (Suttocide A ) polymethoxy Er Huan oxazolidine (Nuosept C ) acetyl Er Jia diox (dimethoxane) thiomersalate (thimersal) dybenal captan adermykon dichlorophen methaform glyceryl laurate ester halogenated diphenyl ether

2,4,4 '-three chloro-2 '-hydroxyl-diphenyl ether (triclosan  or TCS)

2,2 '-dihydroxy-5,5 '-two bromo-diphenyl ether phenolic compounds

Phenol

The 2-methylphenol

The 3-methylphenol

The 4-methylphenol

The 4-ethyl-phenol

2, the 4-xylenol

2, the 5-xylenol

3, the 4-xylenol

2, the 6-xylenol

4-n-pro-pyl phenol

4-normal-butyl phenol

4-n-pentyl phenol

The 4-tert-amyl phenol

4-n-hexyl phenol

4-n-heptyl phenol list or many alkyl and aryl halide substituting phenol

Parachlorophenol

The methyl parachlorophenol

The ethyl parachlorophenol

The n-pro-pyl parachlorophenol

The normal-butyl parachlorophenol

The n-pentyl parachlorophenol

The sec-amyl parachlorophenol

The n-hexyl parachlorophenol

The cyclohexyl parachlorophenol

The n-heptyl parachlorophenol

The n-octyl parachlorophenol

O-chlorphenol

The methyl o-chlorphenol

The ethyl o-chlorphenol

The n-pro-pyl o-chlorphenol

The normal-butyl o-chlorphenol

The n-pentyl o-chlorphenol

The tertiary pentyl o-chlorphenol

The n-hexyl o-chlorphenol

The n-heptyl o-chlorphenol

Adjacent benzyl parachlorophenol

Methyl parachlorophenol between adjacent benzyl

Between adjacent benzyl, a dimethyl parachlorophenol

Adjacent phenethyl parachlorophenol

Methyl parachlorophenol between adjacent phenethyl

3-methyl parachlorophenol

3,5-dimethyl parachlorophenol

6-ethyl-3-methyl parachlorophenol

6-n-pro-pyl-3-methyl parachlorophenol

6-isopropyl-3-methyl parachlorophenol

2-ethyl-3,5-dimethyl parachlorophenol

6-sec-butyl-3-methyl parachlorophenol

2-isopropyl-3,5-dimethyl parachlorophenol

6-diethylmethyl-3-methyl parachlorophenol

6-isopropyl-2-ethyl-3-methyl parachlorophenol

2-sec-amyl-3,5-dimethyl parachlorophenol

2-diethylmethyl 3,5-dimethyl parachlorophenol

6-secondary octyl-3-methyl parachlorophenol

Parachlorometacresol

P bromophenol

The methyl p bromophenol

The ethyl p bromophenol

The n-pro-pyl p bromophenol

The normal-butyl p bromophenol

The n-pentyl p bromophenol

The sec-amyl p bromophenol

The n-hexyl p bromophenol

The cyclohexyl p bromophenol

Adjacent bromophenol

The adjacent bromophenol of tertiary pentyl

The adjacent bromophenol of n-hexyl

N-pro-pyl-,-the adjacent bromophenol of dimethyl

The 2-phenylphenol

4-chloro-2-methylphenol

4-chloro-3-methylphenol

4-chloro-3, the 5-xylenol

2,4-two chloro-3,5-xylenol

3,4,5,6-tetrabromobisphenol-methylphenol

5-methyl-2-amyl phenol

4-isopropyl-3-methylphenol

Parachlorometaxylenol (PCMX)

Chlorothymol

Phenyl phenol

The phenoxy group isopropyl alcohol

5-chloro-2-hydroxyl diphenyl methane resorcinol and derivant thereof

Resorcinol

Methylresorcinol

Ethyl resorcinol

The n-pro-pyl resorcinol

N-butyl resorcinol

The n-pentyl resorcinol

The n-hexyl resorcinol

The n-heptyl resorcinol

The n-octyl resorcinol

The n-nonyl resorcinol

The phenyl resorcinol

The benzyl resorcinol

The phenethyl resorcinol

The phenylpropyl resorcinol

The p-chlorobenzyl resorcinol

5-chloro-2,4-dihydroxy diphenyl methane

4 '-chloro-2,4-dihydroxy diphenyl methane

5-bromo-2,4-dihydroxy diphenyl methane

4 '-bromo-2,4-dihydroxy diphenyl methane

Bisphenol compound

2,2 '-di-2-ethylhexylphosphine oxide (4-chlorophenol)

2,2 '-di-2-ethylhexylphosphine oxide (3,4, the 6-trichlorophenol, 2,4,6,-T)

2,2 '-di-2-ethylhexylphosphine oxide (4-chloro-6-bromophenol)

Two (2-hydroxyl-3,5-chlorophenesic acid) thioether

Two (2-hydroxyl-5-benzyl chloride base) thioether

Benzoate (p-Hydroxybenzoate)

Methyl parahydroxybenzoate

Propyl p-hydroxybenzoate

Butyl p-hydroxybenzoate

Ethylparaben

P-Hydroxybenzoic acid isopropyl ester

P-Hydroxybenzoic acid isobutyl ester

Benzyl p-hydroxybenzoate

Sodium Methyl Hydroxybenzoate

Sodium Propyl Hydroxybenzoate

The halogenation carbanilide

3,4,4 '-trichloro-symmetrical diphenyl urea (triclocarban Triclocarban  or TCC)

3-trifluoromethyl-4,4 '-the dichloro carbanilide

3,3 ', the 4-trichloro-symmetrical diphenyl urea

Be applicable to that other antibacterial of the present invention is known as " natural " antimicrobial acivity composition, is also referred to as natural essence oil.The title of these active component comes from its natural former plant.Typical natural plant essence oil antimicrobial acivity composition comprises Pimpinella anisum Linn., Fructus Citri Limoniae, Citrus, Herba Rosmarini Officinalis, Ilicis Purpureae, Herba thymi vulgaris, Garden lavender, Flos Caryophylli, Flos lupuli (Flos Humuli Lupuli), Camellia sinensis, Herba Cymbopogonis Citrari, Semen Tritici aestivi, Fructus Hordei Vulgaris, lemon grass (Cymbopogon citratus), cedar leaf, cedar wood, Cortex cinnamomi japonici (Ramulus Cinnamomi), Flos Inulae flowers and plants (fleagrass), Herba Erodii, sandalwood, violet, Pericarpium Citri tangerinae, Eucalyptus, Herba Verbenae, Herba Menthae, Resin benzoin, basil, Fructus Foeniculi, fir, balm, menthol, ocmea origanum (Adeps Bovis seu Bubali), Hydastiscarradensis, berberidaceae daceae (Berberidaceae), the oil of plant such as ratanhia and Rhizoma Curcumae Longae.The main chemical compositions that wherein also comprises plants essential oil with antibacterial action.This class chemical constituent comprises anethole, catechol, camphene, carvacrol, eugenol, eucalyptole, ferulic acid, farnesol, chamenol, tropolone, limonene, menthol, methyl salicylate, thymol, terpinol, verbenone, berberine, ratanhia extract, oxidation caryophyllene, citronellic acid, curcumin, nerolidol and geraniol.

Other active component has antibacterial metal salts.This constituents generally comprises 3b-7b, 8 and 3a-5a family slaine.Specifically be aluminum, zirconium, zinc, silver, gold, copper, lanthanum, stannum, hydrargyrum, bismuth, selenium, strontium, scandium, yttrium, cerium, praseodymium, neodymium, hard iron, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutecium and their mixture.

The antibacterial that preferably is applicable to this is the broad-spectrum anti-microbial activity composition, is selected from triclosan , triclocarban , Octopirox, PCMX, ZPT, natural essence oil and main component thereof, and their mixture.Most preferably being used for antimicrobial acivity composition of the present invention is triclosan .B. anion surfactant

Leave-on antimicrobial compositons of the present invention contains the 0.05-10% (weight) that accounts for retention type composition weight, preferred 0.1-2% (weight), the more preferably anion surfactant of 0.2-1% (weight).Although there is no particular determination in theory, it is generally acknowledged that anion surfactant can destroy the lipid in the bacterial cell membrane.Be applicable to that this specific acid can reduce the negative charge of bacteria cell wall, penetrate the cell membrane that is weakened by surfactant, make the Cytoplasm acidify of antibacterial.So the easier cell wall that penetrates reduction of antimicrobial acivity composition, and more effectively kill antibacterial.

The non-limiting example that is applicable to present composition anion foaming surfactant sees McCutcheon work " detergent and emulsifying agent " North America version (1990, ManufacturingConfectioner Publishing Co. publishes); McCutcheon work " functional components " North America version (1992); And US3929678 (people such as Laughlin, 1975.12.30 authorizes), all be incorporated herein by reference.

Various anion surfactants all may be applicable to the present invention.The non-limiting example of anion foaming surfactant comprises: alkyl sulfate and alkyl ether sulfate; the sulphation monoglyceride; sulfonation alkene; alkylaryl sulfonates; uncle or secondary alkyl sulfonate; alkyl sulfo succinate; acyl taurine salt; acyl-hydroxyethyl sulfonate; alkyl glycerol ether sulfonate; methylmesylate; alpha-sulfonated fatty acid; alkylphosphonic; acyl glutamate; acyl sarcosinates; alkyl sulfoacetate; acylated peptide; the alkyl ether carboxy acid salt; acyl-lactate; anion fluoro surfactants and their mixture.Anionic surfactant mixture can be effective to the present invention.

The anion surfactant that is applicable to this Cleasing compositions comprises alkyl sulfate and alkyl ether sulfate.The representative formula of this constituents is R ¹O-SO ₃M and R ¹(CH ₂H ₄O) _x-O-SO ₃M, wherein R ¹Be the saturated or unsaturated straight or branched alkyl that contains 8-24 carbon atom, x is 1-10, and M is a water-soluble cationic, as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.Alkyl sulfate generally carries out sulphation by single hydroxyl alcohol (containing 8-24 carbon atom) through sulfur trioxide or other sulphation technology and makes.Alkyl ether sulfate is generally made through sulphation by the condensation product of oxirane and single hydroxyl alcohol (containing 8-24 carbon atom).This class alcohol can be made as cocos nucifera oil or Adeps Bovis seu Bubali by fat, also can be through synthetic.The instantiation that is applicable to the alkyl sulfate of this Cleasing compositions has lauryl or myristyl sodium sulfate salt, ammonium salt, potassium salt, magnesium salt or triethanolamine salt.The example of the alkyl ether sulfate that is suitable for comprises lauryl ether-3 ammonium sulfate, sodium salt, magnesium salt or triethanolamine salt.

Other anion surfactant that is suitable for has the sulphation monoglyceride, and its form is R ¹CO-O-CH ₂-C (OH) H-CH ₂-O-SO ₃M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl that contains 8-24 carbon atom, M is water-soluble cationic such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.They are generally formed monoglyceride, are made through the sulfur trioxide sulphation then by glycerol and fatty acid (containing 8-24 carbon atom) reaction.The example of sulphation monoglyceride is a cocos nucifera oil monoglyceride sodium sulfate.

Other anion surfactant that is suitable for comprises alkene sulfonate, and its form is R ¹SO ₃M, R ¹Be the monoene that contains 12-24 carbon atom, M is water-soluble cationic such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.This compounds can be made by following method, and alpha-olefin is SO 3 sulfonated through what do not cooperate, this acid reaction chemical compound that neutralizes then, and formed sultone obtains corresponding hydroxyl alkane sulfonate through hydrolysis in the reaction.The example of sulfonation alkene is C ₁₄/ C ₁₆The alpha-olefin sodium sulfonate.

Other anion surfactant that is suitable for is a linear alkylbenzene sulfonate (LAS), and its form is R ¹-C ₆H ₄-SO ₃M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl that contains 8-24 carbon atom, M is water-soluble cationic such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.This chemical compound can be by linear alkylbenzene (LAB) and SO 3 sulfonated making.The example of this anion surfactant is a dodecylbenzene sodium sulfonate.

Other anion surfactant that is applicable to this Cleasing compositions comprises uncle or secondary paraffin sulfonate, and its form is R ¹SO ₃M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl that contains 8-24 carbon atom, M is water-soluble cationic such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.It is generally made through the sulfur dioxide sulfonation by alkane in the presence of chlorine and ultraviolet, or is made by other known method of sulfonating.Sulfonation can take place on the secondary of alkyl chain or uncle position.The example of alkane sulfonate is C among the present invention _13-17Alkane sulfonic acid alkali metal salts or ammonium salt.

Other anion surfactant that is suitable for has alkyl sulfo succinate, comprising N-octadecyl sulfosuccinamic acid disodium; Lauryl 2-Sulfosuccinic acid diammonium; N-(1,2-two carboxyethyls)-N-octadecyl 2-Sulfosuccinic acid four sodium; The sodium sulfosuccinate diamyl ester; The sodium sulfosuccinate dihexyl; And sodium sulfosuccinate dioctyl ester.

Taurate based on taurine also is suitable for, and the former is also referred to as the 2-aminoethane sulphonic acid.The example of taurine comprises the N-alkyl taurine, and it is made by the reaction of lauryl amine and sodium isethionate, referring to US2658072, in conjunction with in the present invention as a reference.Other example based on taurine comprises the acyl group taurine, and it is made by n-N-methyltaurine and fatty acid (containing 8-24 carbon atom) reaction.

The another kind of anion surfactant that is applicable to this Cleasing compositions has acyl isethinate.This acyl isethinate is suc as formula R ¹CO-O-CH ₂CH ₂SO ₃Shown in the M, R wherein ¹Be the saturated or undersaturated straight or branched alkyl that contains 10-30 carbon atom, M is a cation.It is generally made by the alkali metal salt reaction of fatty acid (containing 8-30 carbon atom) with isethionic acid.The non-limiting example of acyl isethinate comprises cocoyl isethionic acid ammonium, cocoyl hydroxyethyl sulfonate, lauroyl hydroxyethyl sulfonate, and their mixture.

Other anion surfactant that is suitable for also has alkyl glyceryl ether sulfonate, and its form is R ¹-OCH ₂-C (OH) H-CH ₂-SO ₃M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl that contains 8-24 carbon atom, M is water-soluble cationic such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.It can be made by epoxychloropropane and sodium sulfite and aliphatic alcohol (containing 8-24 carbon atom) reaction, or is made by other method.One of example is a cocoyl glycerin ether sodium sulfonate.

Other anion surfactant that is suitable for comprises formula R ¹CH (SO ₄The alpha-sulfonated fatty acid of)-COOH and and formula R ¹CH (SO ₄)-CO-O-CH ₃Sulfonated formate, R wherein ¹It is the saturated or undersaturated straight or branched alkyl that contains 8-24 carbon atom.It can be made through SO 3 sulfonated by fatty acid or alkyl methyl ester (containing 8-24 carbon atom), or is made by other known sulfonation technology.The example comprises α-sulfonation fatty acid distribution of coconut oil and lauryl methyl ester.

Other anionic species comprises phosphate, and as monoalkyl, dialkyl group and trialkyl phosphate, it is made by five phosphorous oxide and monohydroxy side chain that contains 8-24 carbon atom or straight chain alcohol reaction.Also can make by other known phosphorylation method.The example of this class surfactant is singly-or two-lauryl sodium phosphate.

Other anionic species comprises acyl glutamate, and corresponding formula is R ¹CO-N (COOH)-CH ₂CH ₂-CO ₂M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl that contains 8-24 carbon atom, M is a water-soluble cationic.Its non-limiting example comprises sodium lauroyl glutamate, and the cocoyl sodium glutamate.

Other anion component comprises the alkanoyl sarcosinate, and corresponding formula is R ¹CON (CH ₃)-CH ₂CH ₂-CO ₂M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl or alkenyl that contains 10-20 carbon atom, M is a water-soluble cationic.Its non-limiting example comprises sodium N-lauroyl sarcosinate, cocoyl sodium sarcosinate and lauroyl sarcosine ammonium.

Other anion component comprises the alkyl ether carboxy acid salt, and corresponding formula is R ¹(OCH ₂CH ₂) _x-OCH ₂-CO ₂M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl or alkenyl that contains 8-24 carbon atom, x is 1-10, and M is a water-soluble cationic.Its non-limiting example comprises the lauryl ether carboxylic acid sodium.

Other anion component comprises acyl-lactate, and corresponding formula is R ¹CO-[O-CH (CH ₃)-CO] _x-CO ₂M, wherein R ¹Be the saturated or undersaturated straight or branched alkyl or alkenyl that contains 8-24 carbon atom, x is 3, and M is a water-soluble cationic.Its non-limiting example comprises the cocoyl sodium lactate.

Other anion component comprises carboxylate, and its non-limiting example comprises the lauroyl carboxylic acid sodium, cocoyl carboxylic acid sodium, and lauroyl carboxylic acid ammonium.Anionic fluorosurfactants also is suitable for.

The chain length of anion surfactant of the present invention can be 8 to 24 carbon atoms, preferred 10 to 18 carbon atoms, most preferably 12 to 16 carbon atoms.Bound by theory not thinks that chain length is that the surfactant and the cell membrane of 12 to 16 carbon atoms produces best biological interaction.

Any counter cation M is applicable in the anion surfactant.Preferred counter cation is selected from sodium, potassium, ammonium, monoethanolamine, diethanolamine and triethanolamine.More preferably counter cation is an ammonium.

When being used for the surfactant of leave-on antimicrobial compositons of the present invention, selection should consider 2 factors: the activity of (1) surfactant molecule in bacterial cell membrane; And the mildness of (2) surfactant, it can influence the mildness index (seeing below) of bactericidal composition.The mildness of biological activity/surfactant

In general, the biological activity of surfactant is high more, and the time-delay activity of compositions that contains this surfactant is big more.But in general, the biological activity of surfactant and its mildness are inversely proportional to; The biological activity of surfactant is high more, and its zest is high more, and the biological activity of surfactant is low more, and it is soft more.No matter be biologically active but the surfactant that stimulates, the still active but surfactant of gentleness of inanimate object all depends on certainly or influences other components selection.

Can directly measure the biological activity/mildness of the pure surfactant that characterizes by the microcytotoxicity index by microcytotoxicity reaction test (analytical method that sees below part).Wherein " pure surfactant " is meant the chemical composition that is made of a kind of surfactant entity substantially, and wherein this entity has only a chain length, end group and salify counter ion basically.For the viewpoint of high bioactivity, the microcytotoxicity index of Response that is preferred for the anion surfactant of leave-on antimicrobial compositons of the present invention is lower than 150, more preferably less than 100, most preferably is lower than 50.For the viewpoint of mildness, the microcytotoxicity index of Response of anion surfactant that is preferred for antimicrobial cleansing compositions of the present invention is greater than 25, more preferably greater than 50, most preferably greater than 100.The microcytotoxicity index of Response is that the surfactant of 25-150 generally has medium biological activity and medium mildness.

Surface activator composition generally is a surfactant mixture, rather than pure surfactant (comprises " technical grade " surfactant, wherein generally comprise the mixture of the entity of different chain length, wherein also may contain high-load impurity), be difficult for measuring biological activity or mildness by the microcytotoxicity index of Response of each surface active agent composition.When said composition is mixture, can measure the microcytotoxicity index of each independent component, if all components in the compositions all is known, then its weighted mean can be used as index.If each component is not known in the compositions, the then main chain end group of surfactant and the more suitable index of chain length as biological activity/mildness.

For the viewpoint of high bioactivity, the chain length of anion surfactant or surfactant mixture is 8-24 carbon atom substantially, is preferably 10-18 carbon atom, most preferably is 12-16 carbon atom.Here used term " substantially " refers to be at least 50%.For the viewpoint of mildness, preferably reduce to C ₁₂

For bioactive viewpoint, the end group of preferred anionic surfactant is lower than 15 dusts, preferably is lower than 10 dusts, more preferably less than 7 dusts." end group " is meant hydrophilic (nonhydrocarbon) part of anion surfactant, counts molecular chain-end from first polarity atom.The size of end group will be predicted according to the van der Waals radius of atom and the configuration of surfactant molecule.The end group that size is lower than 7 dusts comprises sulfate radical, sulfonate radical and phosphate radical.For the viewpoint of mildness, preferred end group is preferably greater than 10 dusts greater than 7 dusts.End group greater than 10 dusts comprises ethoxylation sulfate radical, glyceryl ether sulfonic acid root and isethionic acid root.Size that it is generally acknowledged end group is big more, prevents in the cell wall that the destructive stearic class blockage of surfactant is many more, and biological activity will reduce, and mildness increases.

The mildness of surfactant or surfactant mixture also can be measured through many conventional methods that become known for measuring the surfactant mildness.For example " Dermatology research impurity " (J.Invest.Dermatol., 1975,64,190-195 page or leaf) and the sealing coat failure test that proposes in US4673525 (people such as Small, 1987.6.16 authorizes), described content all is combined in herein as a reference.In general, surfactant is gentle more, and the destructiveness of skin sealing coat is low more in the sealing coat failure test.Enter in the detected solution of the diffuser casing that contains physiologic buffer through the respective amount of radiolabeled water by measuring, measure the destruction of skin sealing coat by epidermis.Skin sealing coat osmotic value has suitable mildness near the surfactant of 0-75 relatively.Relative skin sealing coat osmotic value has zest greater than 75 surfactant.

For making said composition effective, must take into account the mildness of surfactant and acid in the biological activity of surfactant and the compositions simultaneously.

For example, ammonium lauryl sulfate (ALS) has high biological activity (microcytotoxicity index=1.0).Because the activity of ALS, though with the antibacterial activity composition of low content and shared to proton reagent, the compositions that contains ALS still has the antimicrobial acivity of extremely effectively delaying time.But contain in the compositions of ALS and also need add cosurfactant or polymer (seeing non-essential component portion) to reach the most preferred mildness of the present invention.

Select for use lauryl ether-3 ammonium sulfate (microcytotoxicity index=120) can make compositions as mild as a dove, but, need to adopt high-load proton reagent and the antimicrobial acivity composition given for reaching the present invention's effect of delaying time as surfactant.

Having little end group, average chain length and be 15.5 alkane sulfonate is active higher surface activity agent, and it is purchased grade product is the HastapurSAS  by name that is produced by Hoechst Celanese.The active component and the sour compositions that contain low content can be shared with high-load alkane sulfonate, and wherein surfactant plays most of effect to the time-delay effect of compositions.Also can be in the compositions with the alkane sulfonate of low content with obviously more high-load active component is shared, to obtain gentleness and effective composition.

The non-limiting example that is applicable to preferred anionic surfactants surfactant of the present invention comprises that chain length is mainly the alkylsurfuric acid ammonium and the alkyl sodium sulfate of 12-14 carbon atom, and alkyl ether ammonium sulfate and sodium alkylether sulphate, chain length is mainly the olefin sulphates of 14-16 carbon atom, and chain length is the alkane sulfonate of 13-17 carbon atom and their mixture.What especially preferably be applicable to this is ammonium lauryl sulfate and sodium lauryl sulfate; Myristyl ammonium sulfate and Semen Myristicae sodium sulfate; Lauryl ether-1 is to the ammonium sulfate and the sodium salt of lauryl ether-4; C _14-16Alkene sulfonate, C _13-17Alkane sulfonate and their mixture.

Found non-anion surfactant, comprised non-ionic surface active agent, cationic surfactant, amphoteric surfactant and composition thereof, this advantage of effect in fact can suppress to delay time.It is believed that these surfactants have disturbed the rupturing of the lipid in the anion surfactant cell membrane.In compositions, the ratio of the amount of these non-ionic surface active agents and anion surfactant should be lower than 1: 1, preferably is lower than 1: 2, more preferably less than 1: 4.

Leave-on antimicrobial compositons of the present invention does not preferably contain water hydrotropy sulfonate, especially the salt of terpenoid, or the salt of the aromatic compound of list or double-core, as camsilate, toluene fulfonate, xylenesulfonate, cumene sulfonate and naphthalene sulfonate.C. give proton reagent

Leave-on antimicrobial compositons of the present invention contain account for retention type composition weight 0.1% to 10% give proton reagent, preferred 0.5% to 8%, more preferably 1% to 5%." give proton reagent " be meant can after the use on skin the acid compound of non-dissociated acid or its mixture.Giving proton reagent can be organic acid, comprises polymeric acid, mineral acid or their mixture.Organic acid

At least can partly keep not dissociating in clean compositions as organic acid to proton reagent.This class is organic directly adds in the compositions for the form that proton reagent can acid, or the enough strong separate acid of conjugate base by adding required acid and capacity is to be formed non-dissociated acid by conjugate base.Buffer capacity

Select and composite preferred organic proton reagent of giving according to its buffer capacity and pKa value.Buffer capacity is defined as, under the pH value condition of product, and the amount (weight %) of the proton that those pKa values can provide less than 6.0 acidic-group in prescription.Buffer capacity both can be calculated also and can calculate with pH with pKa, and calculate (ignoring any) greater than 6.0 pKa with the acid and the concentration of conjugate base, perhaps can determine (titration end-point pH=6.0) by the method for simple acid base titration with sodium hydroxide or potassium hydroxide.

Preferred organic buffer capacity of proton reagent of giving is greater than 0.005%, more preferably greater than 0.01%, especially more preferably greater than 0.02%, most preferably greater than 0.04% in the sterilizing cleaning compositions of the present invention.Mineral acid

In clean compositions, can not keep the state of not dissociating as mineral acid to proton reagent.However, find that still mineral acid can be in the present invention as effectively giving proton reagent.There is no particular determination in theory, but think that strong inorganic acid can make proteinic carboxyl and phosphatidyl acidify in the Skin Cell, acid thereby the formation original position does not dissociate.This class can only directly add in the compositions for proton reagent with the form of acid.pH

A key that reaches beneficial characteristics of the present invention is that the non-dissociated acid that forms (deposition or original position form) to proton reagent is retained on the skin with protonated form.Therefore, the pH of antimicrobial cleansing compositions of the present invention should be transferred to enough low so that on skin, form or deposit a large amount of not disassociation acid.The pH of compositions should be adjusted to, more preferably be buffered to 3.0 to 6.0, is preferably 3.0 to 5.0, and more preferably 3.5 to 4.5.

The organic acid non-exclusionism example that can be used as to proton reagent has: adipic acid, tartaric acid, citric acid, maleic acid, malic acid, succinic acid, glycolic, 1,3-propanedicarboxylic acid, benzoic acid, malonic acid, salicylic acid, gluconic acid, polymeric acid, their salt and their mixture.The non-exclusionism example that is used for this mineral acid has hydrochloric acid, phosphoric acid, sulphuric acid and their mixture.

Owing to compare with other acid, polymeric acid is low to the zest of skin, based on this point, especially preferably uses it for the present invention.Term " polymer " acid used herein " be meant the acid that on a chain, is connected with the carboxyl repetitive.The polymeric acid that is suitable for comprises homopolymer, bipolymer and terpolymer, but wherein should contain 30% (mol) carboxyl at least.The particular instance that is applicable to this polymeric acid comprises poly-(acrylic acid), with the copolymer of they and ion and nonionic composition (for example, maleic acid-acrylic acid, sulfonic acid-acrylate and styrene-propene acid copolymer), the molecular weight of these cross linked polyacrylates is lower than 250,000, preferably be lower than poly-(Alpha-hydroxy) acid of 100,000, poly-(methacrylic acid), with natural polymeric acid such as chondrus ocellatus Holmes acid, carboxymethyl cellulose and the alginic acid of existing.Here especially preferred straight chain gathers (acrylic acid).Water

The water that contains 0-99.85% (weight) in the leave-on antimicrobial compositons of the present invention is preferably 3-98% (weight), and more preferably 5-97.5% (weight) most preferably is 38-95.99% (weight).

Apparent viscosity or the clean viscosity of leave-on antimicrobial compositons of the present invention under 26.7 ℃ is preferably 500-60, and 000cps is preferably 5,000-30,000cps.Unless otherwise indicated, being used for term of the present invention " viscosity " adopts Brookfield RVTDCP, CP-41 rotor to measure through 3 minutes under 1 rev/min of condition." only " viscosity is meant the viscosity of undiluted liquid cleaner.E. preferred non-essential composition mildness promoter

For reaching mildness of the present invention, can add the non-essential composition that to promote the skin mildness.These compositions comprise cation and non-ionic polymers, cosurfactant, humidizer and their mixture.The polymer that is applicable to this comprises Polyethylene Glycol, polypropylene glycol, hydrolyzed silk protein, hydrolysis milk proem, hydrolysis of keratin, guar gum hydroxypropyl-trimethyl ammonium chloride (trimonium chloride), polyquaternary ammonium salt, siloxane polymer and their mixture.During use, mildness promotes the consumption of polymer to account for the 0.1-1% (weight) of leave-on antimicrobial compositons, is preferably 0.2-1% (weight), more preferably 0.2-0.6% (weight).The cosurfactant that is applicable to this comprises ethoxylated alcohol, POE (20) Isosorbide Dinitrate monoleate (Tween  80), Polyethylene Glycol cocos nucifera oil ester and the Pluronic  propylene oxide/ethylene oxide block copolymer of non-ionic surface active agent such as Genapol  24 series, and amphoteric surfactant such as alkyl betaine, alkyl sulfobetaines, alkyl both sexes acetas, alkyl both sexes diacetate esters, alkyl both sexes propionic ester and alkyl both sexes dipropionate.During use, the gentle cosurfactant that promotes accounts for the 20-70% (weight) of retention type composition weight, is preferably 20-50% (weight) anion surfactant.

The mildness reinforcing agent of other class is the skin moisturizing agent of lipid, and the user that they can be retention type compositions provides the effect of humidification, because lipophilic skin moisturizing agent meeting deposits on the skin of user.When in the antimicrobial retention type compositions that it is applied in here, the consumption of lipotropy skin moisturizing agent is 0.1% to 30% of a composition weight, is preferably 0.2% to 10%, most preferably is 0.5% to 5%.

Under some situation, also wish to limit lipophile skin heating agent, see " cosmetics and toilet articles " 103 volumes with its solubility parameter, and the 47-69 page or leaf (in October, 1988, Vaughan).The Vaughen solubility parameter (VSP) that is applicable to the lipophile skin moisturizing agent in the antimicrobial cleansing compositions of the present invention is 5-10, is preferably 5.5-9.

Various lipid components and their mixture all are suitable in antimicrobial cleansing compositions of the present invention.Preferred lipophile skin condition composition is selected from: hydrocarbon ils and wax, polysiloxanes, derivative of fatty acid, cholesterol, cholesterin derivative, two-and the Three-glycerol ester, vegetable oil, vegetable oil derivatives, the liquid nondigestible oil, see US 3600186 (Marrson, on August 17th, 1971 authorized), 4005195 and 4005196 (people such as Jandacek, all authorize) on January 25th, 1977, all in conjunction with in the present invention as a reference, or be selected from the mixture that liquid easily digests oil or nondigestible oil and solid polyalcohol polyester, see US 4797300 (Jandacek, on January 10th, 1989 authorized); US 5306514,5306516 and 5306515 (Letton; All authorize on April 26th, 1994), all in conjunction with in the present invention as a reference, and be selected from acetyl group glyceride, Arrcostab, alkenyl esters, lanoline and derivant thereof, newborn triglyceride, wax ester, Cera Flava derivant, sterol, phospholipid and their mixture.Fatty acid, fatty acid soaps and water-soluble polyol do not belong to the limited range of the present invention to the agent of lipid skin moisturizing.

Hydrocarbon ils and wax: some example has vaseline, mineral oil, microwax, polyolefin (for example hydrogenation and not hydrogenated polybutene and poly decene), paraffin, ceresin, ceresine, polyethylene and perhydro-squalene.The blend of vaseline and hydrogenation and not hydrogenation high molecular polybutene also is suitable for being used as the agent of lipid skin moisturizing in the present composition, wherein the amount ratio of vaseline and polybutene is 90: 10 to 40: 60.

Silicone oil: some example has dimethicone copolyol, dimethyl polysiloxane, diethyl polysiloxanes, high molecular dimethyl polysiloxane, C ₁-C ₃₀Pure and mild their mixture of mixed alkyl polysiloxanes, phenyl dimethyl polysiloxane, dimethyl polysiloxane.Preferred non-volatile polysiloxanes is selected from dimethyl polysiloxane, dimethyl polysiloxane alcohol, C ₁-C ₃₀Mixed alkyl polysiloxanes and their mixture.Be applicable to the nonlimiting examples US 5011681 (people such as Ciotti, on April 30th, 1991 authorized) of this polysiloxanes, in conjunction with in the present invention as a reference.

Two and triglyceride: some example is Oleum Ricini, soybean oil, soybean oil derivative such as maleinization soybean oil, safflower oil, Oleum Gossypii semen, Semen Maydis oil, walnut oil, Oleum Arachidis hypogaeae semen, olive oil, cod-liver oil, almond oil, American Avocado Tree oil, Petiolus Trachycarpi oil and Oleum sesami, vegetable oil and vegetable oil derivatives; Oleum Cocois and coconut oil derivative, Oleum Gossypii semen and Oleum Gossypii semen derivant, simmondsia oil, cocoa butter etc.Aceto-glyceride also is suitable for, and the example has acetylated monoglyceride.

Preferred lanoline and the derivant thereof of adopting, example comprises lanoline, lanolin oil, lanolin wax, lanolin alcohol, lanolin fatty acid, isopropyl lanolate, acetylated lanolin, Acetylated lanolin alcohols., linoleic acid lanoline alcohol ester, castor oil acid lanoline alcohol ester.

Most preferably have at least 75% to be selected from following lipid component in the lipophile skin conditioning agent: the blend of vaseline, vaseline and polyphosphazene polymer butylene, mineral oil, liquid nondigestible oil (for example liquid Oleum Gossypii semen sucrose octaester), or liquid easily digests the mixture of oil or nondigestible oil and solid polyalcohol polyester (for example by C ₂₂The sucrose octaester of fatty acid preparation), wherein easily to digest the amount ratio of oil or nondigestible oil and solid polyalcohol polyester be 96: 4 to 80: 20 to liquid, hydrogenation or not hydrogenated polybutene, microwax, polyolefin, paraffin, ceresin, ceresine, polyethylene, perhydro-squalene, dimethyl polysiloxane, alkylsiloxane, polymethyl siloxane, methyl phenyl silicone and their mixture.When using the mixture of vaseline and other lipid, carat be preferably 10: 1 to 1: 2, more preferably 5: 1 to 1: 1 with the amount ratio of other lipid of selecting for use (hydrogenation or not hydrogenated polybutene or poly decene or mineral oil).Stabilizing agent

In the antimicrobial compositions of the present invention with the agent of lipophile skin moisturizing when the mildness promoter, also contain the stabilizing agent that accounts for antimicrobial cleansing compositions weight 0.1% to 10% in the compositions, be preferably 0.1% to 8%, more preferably 0.1% to 5%.

Stabilizing agent is used for forming the crystal stability network structure in retention type compositions, prevents that the drop cohesion or the product of lipophile skin heating agent is separated.Network structure has time dependent viscosity recovery characteristic (for example thixotropy) after the shearing strain effect.

The stabilizing agent that is applicable to this is not a surfactant.Stabilizing agent can improve to be stored and stress stability.Some preferred hydroxyl stabilizing agent comprises 12-hydroxy stearic acid, 9,10-dihydroxystearic acid, three-9,10-dihydroxystearic acid glyceride and three-12-hydroxy stearic acid glyceride (mainly containing three-12-hydroxy stearic acid glyceride in the castor oil hydrogenated).Three-12-hydroxy stearic acid glyceride most preferably is used for compositions of the present invention.When using the hydroxyl crystal stabilizer in the Cleasing compositions, its consumption accounts for 0.1% to 10% of leave-on antimicrobial compositons weight, is preferably 0.1% to 8%, and more preferably 0.1% to 5%.Stabilizing agent at room temperature or be water-fast under the condition near room temperature.

Perhaps, the stabilizing agent of retention type compositions employing of the present invention can comprise polymer viscosifier.When adopting polymer viscosifier as stabilizing agent in the retention type compositions, its consumption generally accounts for 0.01% to 5% of composition weight, is preferably 0.3% to 3%.Polymer viscosifier is anion preferably, nonionic, cation or hydrophobically modified polymer, being selected from molecular weight is 1,000-3,000,000 guar gum class cationic polysaccharide, by acrylic acid and/or the deutero-anion of methacrylic acid, cation and nonionic homopolymer, anion, cation and non-ionic cellulose resin, dimethyl dialkyl ammonium chloride and acrylic acid cation copolymer, the cationic homopolymer of dimethyl alkyl ammomium chloride, cation polyolefin and ethoxylation polyalkyleneimine, molecular weight are 100,000-4,000,000 Polyethylene Glycol and their mixture.Preferred polymers is selected from sodium polyacrylate, hydroxyethyl-cellulose, cetyl hydroxyethyl cellulose and polyquaternary ammonium salt-10.

Perhaps, used stabilizing agent can comprise C in the retention type compositions of the present invention _10-22Glycol fatty acid ester.C _10-22Glycol fatty acid ester also can be shared with above-mentioned polymer viscosifier.This ester is diester preferably, is more preferably C _14-18Diester most preferably is a diglycol stearate.In retention type compositions, use C _10-22During the glycol fatty acid ester used as stabilizers, its consumption is generally 3% to 10% of retention type composition weight, is preferably 5% to 8%, and more preferably 6% to 8%.

The another kind of stabilizing agent of leave-on antimicrobial compositons of the present invention that is applicable to comprises the dispersibility amorphous silica, is selected from fumed silica and precipitated silica, and their mixture.Used term " dispersibility amorphous silica " is meant little, the noncrystal silicon dioxide of micronization, average coalescent granularity is less than 100 microns.

Fumed silica is also referred to as arc silicon dioxide, Silicon chloride. is hydrolyzed into gas phase makes under the oxyhydrogen flame condition.It is generally acknowledged that the silicon dioxide molecules that firing method makes can condense the formation granule, these granules can be through collision, adhere to sintering and be in the same place.Can obtain three-dimensional side chain aggregation by this method.When aggregation is cooled to the fusing point (1710 ℃) of silicon dioxide when following, further collision can cause the mechanical interlocking of chain, forms aggregate.Precipitated silica and silica dioxide gel generally make in aqueous solution.Referring to the article (in March, 1992) that is entitled as " the CAB-O-SIL  fumed silica in cosmetics and the personal cleanliness's care product " among article (in October, 1993) that is entitled as " characteristic and the function of the undressed fumed silica of CAB-O-SIL  " among the Cabot technical data handbook TD-100 and the Cabot technical data handbook TD-104, described content combination in the present invention as a reference.

The average aggregation size of fumed silica is preferably 0.1 to 100 micron, is preferably 1 to 50 micron, more preferably 10 to 30 microns.Aggregate by particle mean size be 0.01 to 15 micron, be preferably 0.05 to 10 micron, more preferably 0.1 to 5 micron, the aggregation that most preferably is 0.2 to 0.3 micron constitutes.The surface area of silicon dioxide is preferably greater than 50 meters squared per gram, more preferably greater than 130 meters squared per gram, most preferably greater than 180 meters squared per gram.

When amorphous silica was used used as stabilizers, its consumption in Cleasing compositions was generally 0.1% to 10%, was preferably 0.25% to 8%, and more preferably 0.5% to 5%.

The 4th class stabilizing agent that is applicable to leave-on antimicrobial compositons of the present invention is the dispersibility smectic clays, is selected from bentonite, hectorite and their mixture.Bentonite is a colloidal state aluminum sulfate clay.Referring to Merck index the 11st edition (1989) 1062 (164 pages), in conjunction with in the present invention as a reference.Hectorite is the clay that contains sodium, magnesium, lithium, silicon, oxygen, hydrogen and fluorine.Referring to Merck index the 11st edition (1989) 4538 (729 pages), in conjunction with in the present invention as a reference.

When using the smectic clays used as stabilizers in the retention type compositions of the present invention, its consumption is generally 0.1% to 10%, is preferably 0.25% to 8%, and more preferably 0.5% to 5%.

Other known stabilizing agent such as fatty acid and aliphatic alcohol also are applicable to the present composition.Palmic acid and lauric acid especially preferably are applicable to this.Other non-essential composition

Also can contain various non-essential compositions in the present composition." the international cosmetic composition handbook of CTFA has been described various indefinitenesses beauty treatment and the medicinal ingredients that are usually used in the skin care industry field in (nineteen ninety-five the 6th edition, combination in the present invention as a reference in full), all be applicable to the present composition.The 537th page of non-limiting example of listing the function class composition.These function class compositions comprise: abrasive material, anti-acne agents, anticaking agent, antioxidant, binding agent, bio-additive, extender, chelating agen, chemical addition agent, toner, the beauty treatment astringent, the beauty treatment Biocide, denaturant, medicinal astringent, emulsifying agent, external-use analgesic, film former, fragrance component, heat preserving agent, opacifier, plasticizer, antiseptic, propellant, Reducing agent, skin whitener, skin conditioning agent (softening agent, wetting agent, multi-functional composition and covering agent), shielding medicine for skin, solvent, short infusion, hydrotropic solvent, solubilizing agent, suspending agent (non-surface-active agent class), sunscreen, UV absorbent and viscosifier (moisture or anhydrous).The function class composition that is suitable for that other those of ordinary skills know comprises solubilizing agent, sequestering agent and keratolytic etc.II. characteristic

Leave-on antimicrobial compositons of the present invention has following characteristic.A. antibiotic effect

Leave-on antimicrobial compositons of the present invention has antibiotic effect.Time-delay antibiotic effect index to gram negative bacteria

Leave-on antimicrobial compositons of the present invention greater than about 0.3 (sterilization 50%), is preferably greater than about 1.0 (sterilizations 90%) to the time-delay antibiotic effect index of gram negative bacteria, more preferably greater than about 2.0 (sterilizations 99%).Adopt that analytical method part hereinafter is described measures time-delay antibiotic effect index to gram negative bacteria to the antibiotic time-delay efficacy test of colibacillary live body method.This exponential representation be the denary logarithm difference of bacterial concentration between sample and matched group.For example index is that the logarithm value of 0.3 expression sterilization number is 0.3 (Δ log=0.3), represents that promptly bacterial number reduces by 50%.Time-delay antibiotic effect index to gram positive bacteria

Leave-on antimicrobial compositons of the present invention greater than 0.5 (sterilization 68%), is preferably greater than 1.0 (sterilizations 90%) to the time-delay antibiotic effect index of gram positive bacteria, more preferably greater than 2.0 (sterilizations 99%) with most preferably greater than 2.3 (sterilizations 99.5%).Adopt the hereinafter antibiotic time-delay efficacy test of the described live body of analytical method part method mensuration gram positive bacteria time-delay antibiotic effect index to staphylococcus aureus.This exponential representation be the denary logarithm difference of bacterial concentration between sample and matched group.For example index is that the logarithm value of 1.0 expression sterilization numbers is 1.0 (Δ log=1.0), i.e. expression sterilization 90.0%.Instant sterilization index

Leave-on antimicrobial compositons of the present invention has improved instant sterilization functions.Adopt live body health care individual of the present invention to wash one's hands and test the sterilization degree that can determine after once cleaning.Measure after this retention type antimicrobial cleansing compositions once cleans and once clean instant sterilization index greater than about 1.0 (sterilizations 90%), be preferably greater than about 1.5 (sterilizations 96.8%), more preferably greater than about 2.0 (sterilizations 99%), most preferably greater than about 2.3 (sterilizations 99.5%).Index representative be before cleaning and the denary logarithm difference of cleaning the back bacterial concentration.For example index is that the logarithm value of 1.0 expression sterilization values is 1.0 (Δ log=1.0), expression sterilization 90%.B. mildness index

The mildness index of leave-on antimicrobial compositons of the present invention is preferably greater than 0.4, more preferably greater than 0.6 greater than 0.3.Measure the mildness index by forearm contrast coating test of the present invention (FCAT).III. the manufacture method of leave-on antimicrobial compositons

Can adopt art-recognized being used to prepare various forms of retention type method for compositions and prepare leave-on antimicrobial compositons of the present invention.IV. the application process of leave-on antimicrobial compositons

Leave-on antimicrobial compositons of the present invention is applicable at certain hour section inner control gram positive bacteria and propagates.Generally the Cleasing compositions with dosage or effective dose is coated in pending position.Also can be coated on towel, sponge, liner, cotton balls, bubble husband wiping or other applying device through the Cleasing compositions of centre coating with dosage.The effective dose of product generally will be decided on a human needs and use habit.The present composition is generally 0.1-10mg/cm at the cleaning dosage of being washed skin part ², more preferably 0.6-5mg/cm ²

Analytical test method microcytotoxicity reaction test list of references: microcytotoxicity handbook (Microtox Manual): toxicity test handbook, 1992

The I-IV volume; Microbics company.Device: microcytotoxicity M500 toxicity test device; Microbics company

Adopt computer to carry out the described data collection and analysis of above-mentioned document.Step: the 1. preparation (normal concentration: 1000ppm) of sample liquid storage

The sample liquid storage for preparing tested anion surfactant is as the liquid storage of all dilute solutions.Standard " initial concentration " is the highest tested concentration, is 500ppm.If (but adopt the initial concentration of 500ppm can't obtain value of calculation, for example active surfactant has been killed the whole reagent in all diluents, then can be according to the known range adjusting initial concentration of the EC50 value of the surfactant of previous mensuration).The concentration of prepared liquid storage is the twice of initial concentration.

(a) in beaker, add 0.1g (or aequum of regulating on demand) anion surfactant (considering the activity of raw material).

(b) microcytotoxicity diluent (2% sodium chloride, Microbics company) is added to the 100g total amount.

(c) agitating solution is guaranteed abundant mixing.2. the preparation of the reconstruct of microcytotoxicity reagent and measured object

(a) start assay device, make the reagent wells temperature be equilibrated at 5.5 ℃, interrupt cultivating, read Kong Wenzhi and be equilibrated at 15 ℃.

(b) in reagent wells, insert clean tube (Microbics company), add 1.0ml microcytotoxicity reconstituted solutions (distilled water, Microbics company), cooled off 15 minutes.

(c) by in the reagent bottle, adding the standard vial (Fei Shi vibrio, Microbics company) of the refrigerative reconstituted solutions reconstruct of 1.0ml microcytotoxicity acute toxicity reagent rapidly.

(d) the solution 2-3 second in the moving reagent bottle of whirlpool, then reconstruct reagent is refunded in the refrigerative test tube, bottle is put back to reagent wells.Stablized 15 minutes.

(e) 8 test tubes that will fill 500 μ l microcytotoxicity diluent are put into the culture hole of test set as measured object, cool off 15 minutes.3. measured object diluent

By 7 parts of measured object diluents of sample liquid storage preparation.Final volume in all test tubes should be 1.0ml.

(a) 8 empty test tubes are placed test tube rack.

(b) in test tube 1-7, add 1.0ml microcytotoxicity diluent solution.

(c) in test tube 8, add 2.0ml sample liquid storage (1000ppm).

(d) solution with 1.0ml test tube 8 adds in the test tube 7, and mixes the solution in the test tube 7.

(e) continuously the new solution that forms of 1.0ml is changed in next test tube (7 to 6,6 to 5 etc.).From test tube 2, take out 1.0ml solution and abandon.Test tube 1 is the blank phase that only contains the microcytotoxicity diluent.Test tube is put into the test set culture hole by concentration order from low to high to be preserved.These test tubes are answered 8 test tubes of preparation in the corresponding above-mentioned steps 2.Cooled off 15 minutes.4. measured object and sample bioluminescence test

(a) 10 μ l reconstruct reagent are added in 8 pre-cooled test tubes that fill the measured object (containing 500 μ l diluent) of preparation in the step 2.With stable reagent 15 minutes.

(b) open microcytotoxicity data collection and report software (Microbics company), selected " beginning test ", initial concentration (in ppm, being 500ppm when adopting normal concentration) and matched group number (1) and diluent group number (7) are revised in import file name and explanation.Time 1 should be selected 5 minutes, and the time 2 should be selected " nothing ".Press enter key, begin test by space bar then.

(c) will place the reading hole corresponding to the measured object test tube that contains reagent of the blank phase of test, and by " setting ".Treat that test tube appears the back by " reading ", then computer can be collected data.

(d) for test tube correct in the reading hole, by by " reading " key and as calculated machine prompting can carry out reading to remaining 7 test tubes that contain reagent equally.

(e) carried out 8 times all initial readings after, the diluted measured object of 500 μ l is changed in the test tube that contains reagent accordingly.Culture hole is put back in moving or whirling motion mixing again through whirlpool.Computer was through 5 minutes countings, and prompting beginning final reading.

(f) the correct test tube that will fill the measured surface activating agent of reagent and dilution places the reading hole, by " reading ", carries out final reading behind the computer prompted.5. data analysis

The linear regression (with respect to the logarithmic sterilization percent of concentration) that adopts " operation of the data file statistics " option (suggestion is used) in the microcytotoxicity software or make data can calculate the bioluminescence of the microcytotoxicity acute toxicity reagent concentration (in ppm) (EC50 value) by the measured object of initial value reduction by 50%.Can adopt following formula to calculate sterilization percent: Wherein x refers to be in corresponding concentration

The microcytotoxicity index is EC50 value (in ppm).To colibacillary live body time-delay antibiotic effect list of references: Aly, R; Maibach, H.I.; Aust, L.B.; Corbin, N.C.; Finkey, M.B.1994.

1. contain the live body antibacterial action of the antimicrobial soap of 1.5% and 0.8% trichloro-symmetrical diphenyl urea to two kinds of pathogen bacterial strains." cosmetic chemistry association magazine " (J.Soc.Cosmet.Chem.), 35,351-355,1981.

2. measure the intravital method of local antimicrobials." cosmetic chemistry association magazine ", 32,317-323.1. testing program

Adopt following method to measure the time-delay antibiotic effect of liquid and solid soap antimicrobial product.The forearm that is used for the measured is no longer handled through other, adopts the blank soap that does not contain antibacterial to organize in contrast and reports bactericidal action.Antibiotic blank group should not have the time-delay antibacterial action in test.2. the stage before testing

Testing in preceding 7 days requires the measured must not use antimicrobial product.Check the measured before tested, hand skin have wound/breakage can not participate in test, 3. washing methods

(a) wash the both sides forearm once with contrasting to soap, remove dirt or temporary antibacterial.The rinsing forearm is also dry.

(b) laboratory technician goes out 10 * 5 centimetres processing region at the forearm subscript.

(c) laboratory technician tests product with 0.5ml and is applied on the processing region and rubbed 10 seconds.

(d) air-dry arm and mark pilot region (marking about 8.6 square centimeters circle) with rubber-stamp.

(e) on another forearm of tester, mark the zone with rubber-stamp and be used for the reference product evaluation.4. cultural method

(a) escherichia coli inoculum (growth is 18-24 hour under 10536,37 ℃ of the ATCC, in Semen sojae atricolor-casein broth bouillon lyophilizing liquid storage) is adjusted to 10 ⁸Organism/milliliter (transmittance with respect to the blank phase of TSB in the spectrometer is 0.45).

(b) use inoculating loop at the about 3cm in tested position ²Scope in inoculation 10 μ l escherichia coli inoculums, cover Hilltop Chamber (Hilltop Research Inc. product).

(c) repeat this method at the tested position of each forearm.5. bacterial sampling (extraction steps)

(a) in water, use 0.04%KH ₂PO ₄, 1.01%Na ₂HPO ₄, 0.1% trinitrotoluene X-100,1.5%Polysorbate 80 (Spheron MD 30/70), 0.3% lecithin preparation sampling solution, with the HCl of 1N with pH regulator to 7.8.

(b) after the inoculation just in time 60 minutes the time, remove Hilltop Chamber down from sampling point.With 8.6cm ²Sampling cup place on this position.

(c) in cup, add 5ml sampling solution.

(d) gently scrape tested position 30 seconds with the glass policeman, extract antibacterial.

(e) remove sampling solution with pipet, place aseptic label test tube.

(f) with the repeated sampling of 5ml sampling liquid.Back 60 minutes of cultivation this sampling procedure is repeated at each position.6. mensuration bacterial population

(a) use 0.117%Na ₂HPO ₄, 0.022%Na ₂HPO ₄Prepare sulfate buffer solution with 0.85% sodium chloride, and with 1N hydrochloric acid with the pH regulator of solution to 7.2-7.4.

(b) sterilely from test tube, take out 1.1ml sampling solution, containing this solution of coating 0.1ml on trypticase-soy agar of 1.5%Polysorbate80.1ml is placed 9ml sterile phosphate buffer agent, make 1: 10 sampling solution dilution liquid.Repeat this method again and (respectively organize diluent) more than 3 times.

(c) reversing counting chamber was cultivated 24 hours down at 35 ℃.

(d) clump count that forms on the count plate, bacterial population multiply by dilution gfactor (initial sample=10, diluent=100 first, secondary dilution liquid=1000, the rest may be inferred) calculate the result, final result forms bacterium colony unit number (CFU ' s/ml) in every milliliter.7. gauge index

Gram negative bacteria time-delay antibiotic effect index=log ₁₀(CFU ' at blank phase position s/ml)-log ₁₀(CFU ' at test product position is s/ml) to the live body of staphylococcus aureus time-delay antibiotic effect list of references: Aly, R; Maibach, H.I.; Aust, L.B.; Corbin, N.C.; Finkey, M.B.1994.

1. contain the live body antibacterial action of the antimicrobial soap bar of 1.5% and 0.8% trichloro-symmetrical diphenyl urea to two kinds of pathogen bacterial strains." cosmetic chemistry association magazine ", 35,351-355,1981.

(a) staphylococcus aureus inoculum (growth is 18-24 hour under 27217,37 ℃ of the ATCC, in Semen sojae atricolor-casein broth bouillon lyophilizing liquid storage) is adjusted to 10 ⁸Organism/milliliter (transmittance with respect to the blank phase of TSB in the spectrometer is 0.45).

(b) use inoculating loop at the about 3cm in tested position ²Scope in inoculation 10 μ l staphylococcus aureus inoculums, cover Hilltop Chamber (Hilltop Research Inc. product).

(a) in water, use 0.04%KH ₂PO ₄, 1.01%Na ₂HPO ₄, 0.1% trinitrotoluene X-100,1.5%Polysorbate 80,0.3% lecithin preparation sampling solution, with the HCl of 1N with pH regulator to 7.8.

(c) in cup, add 5ml sampling solution.

(e) remove sampling solution with pipet, place aseptic label test tube.

(c) reversing counting chamber was cultivated 24 hours down at 35 ℃.

Gram positive bacteria time-delay antibiotic effect index=log ₁₀(CFU ' at blank phase position s/ml)-log ₁₀(CFU ' at test product position s/ml).Health care individual live test (HCPHWT) list of references of washing one's hands: ASTM standard annual, 11.05 volumes; ASTM name: E1174-94; The standard test method of preparation " the assessment health care individual wash one's hands " 1. use with above-mentioned list of references in similar test method, comprise following change/explanation.

(a) once clean the sampling back and measure the measured, only need once clean data.At least four measured of test requirements document are just effective.

(b) previous data in this scheme (promptly contrasting with soap is not to carry out in each test) in contrast

(c) test material

(growth is 18-24 hour under 25 ℃, in Semen sojae atricolor-casein broth bouillon, and transmittance is 0.45 under spectrophotometer by being diluted to, with concentration adjustment to 10 for Organic substance: serratia marcescens ATCC 14756 ⁸Organism/milliliter)

Diluent: with 1N hydrochloric acid with phosphate buffer (1.5%Polysorbate 80 for 0.1% trinitrotoluene X-100,0.3% lecithin) with pH regulator to 7.2

Agar: the Semen sojae atricolor casein agar that contains 1.5%Polysorbate 80

(d) use program

The experimenter tests retention type compositions with 2.0ml and places tester's hands.The tester applying on hand, rubs compositions 30 seconds then, covers metacarpus, the back of the hand, points and refer to a junction, epidermis and fingernail.Moist hand.

(e) calculate bacterial population by the diluent (1: 10) or the sampling of a series of cultures, the 0.1ml diluent is coated in the counting chamber.The gained result is the sterilization logarithm value that sampling obtains according to benchmark.

Once clean instant sterilization index=Log (CFU ' in the benchmark sampling s)-Log (once clean in the sampling of back CFU ' s)

Clean for ten times instant sterilization index=Log (CFU ' in the benchmark sampling s)-Log (clean for ten times in the sampling of back CFU ' s)

(f) hands of cleaning is immersed decontamination in 15 seconds in 70% ethanol, cleaned 5 minutes with contrast soap and water then.Forearm contrast coating test (FCAT) list of references: Ertel, people such as K.D. " are used to assess the forearm contrast coating technology of the relative mildness of personal cleansing product " " cosmetic chemistry association magazine " 46 (1995) 67-76

Forearm contrast coating test or title FCAT differentiate the controlled trial of product to the difference of skin mildness.Contrast with the cleansing soap matched group and the test product that contain the standard soap.Tested group of restriction

The tested group membership who is adopted comprises 20-30 people, and the age is 18-55 year, washes one's hands by rule with soap.Have should getting rid of of following situation among the selected measured: (1) is in initial trial, the initial degree of drying of forearm is 3.0 or higher, (2) suffer from skin carcinoma, eczema or psoriasis on the forearm, (3) just accepting injection of insulin, (4) be in trimester of pregnancy or age of sucking, or (5) are just being accepted the dermatopathy treatment or are suffering from contact hypersensitive.The measured should avoid hot bath, swimming, Exposure to Sunlight during development test, must not use any soap class, cleaning product, cream frost or gel on its forearm.In at least 2 hours, measured's forearm must not get wet before the classification process.Research adopts double blinding, product order form at random to carry out.Clinical assistants all should be confirmed its nursing order and record before each measured washs.

Products applied 9 times on forearm altogether: use 2 every day in preceding four days, and last day is with 1 time.The supervision detection means, washroom should be 3 hours every minimum.

In the washing process, clinical assistants all wears disposable glove, and rinsing glove in the middle of the nursing need be changed glove for different measured.Reference product

Reference product is the compacting soap bar, wherein contains:

56.1% tallow acid sodium

18.7% coconut oil sodium

0.7% sodium chloride

24% water

0.5% submember (essence, impurity) product application program

Test product and reference product are tested on same arm.Adopt following method of testing.

1. arm is placed under the faucet, drench the whole palmar forearm of measured with 95-100 tap water.

2. clinical assistants is drenched 1/4 Masslinn  towel (about 8 " * 6 ") with tap water, extracts towel gently and removes excessive water.

3. clinical assistants, is coated in product on the forearm near the position of ancon from, and process is as follows:

Fluid product

A. the 0.10cc test product is coated on the center that suitably marks the position with syringe.

B. drench two fingers (forefinger and middle finger) of wearing (latex) glove with the tap water that flows.

C. looping at coating part with the finger of beating temperature makes product bubble for 10 seconds.

D. the foam of coating part kept 90 seconds, then with the tap water rinsing 15 seconds of flowing, noted the not foam of eccysis adjacent regions.After the rinsing 10 seconds, clinical assistants is cleaned this position gently with glove two fingers in residue 5 seconds.

Soap bar products

A. drench two fingers (forefinger and middle finger) of wearing (latex) glove with the tap water that flows.

B. soap bar is simply placed the following temperature of beating of the tap water that flows.Must when begin to test every day, drench tested soap bar with mobile tap water.

C. looped for 15 seconds with the finger friction of drenching on the soap bar surface, make foaming between soap bar and the finger.

D. will be with foamy finger to loop and rub for 10 seconds, on skin, foam at application site.

E. foam kept for 90 seconds at application site, then with the tap water rinsing 15 seconds of flowing, noted the not foam of eccysis adjacent regions.After the rinsing 10 seconds, clinical assistants is cleaned this position gently with glove two fingers in residue 5 seconds.

Wipe product

A. with the cleaning wiping cloth doubling, intersect, carry out wiping gently through looping at suitable position.

B. air-dry this position 90 seconds.Not rinsing.

Retention type product

B. looped for 10 seconds at coating part with glove finger.

C. air-dry this position 90 seconds.Not rinsing.

4. after waiting stop for 90 seconds, the residue coating part on arm repeats above process, implements this process to the wrist direction.

5. at suitable test position repeating step 1-4, apply product 2 times in tested zone.

6. after all coating parts all applied twice product, clinical assistants patted dry measured's arm gently with disposable tissues.

Assessment

The classification expert assesses the skin through every processing after initial and final research is cleaned 3 hours.At controllable light (General Electric Cool White, 22 watts, 8 " Circuline fluorescent lamp), 2.75 x magnifications (the KFM-1A type Luxo enlarger lamp that throws light on, MarshallIndustries, Dayton, 0H) assessment nursing position under the condition.

By the drying property of classification expert assessment and evaluation skin, by following standard grading.

Table 1

Forearm position grade classification rank xerosis cutis 0 moist 1.0 visible slight efflorescence speckle and accidental visible small pieces peeling position.2.0 generalized slight efflorescence.Existence is chapped in early days or accidental visible small pieces rise

The skin zone position.3.0 generalized medium efflorescence and/or severe is chapped and peeling.4.0 generalized severe efflorescence and/or severe is chapped and peeling.5.0 generalized height is chapped and peeling.Exist eczema to change.There is efflorescence,

But it is not obvious.Can find that hemorrhagic chaps.6.0 generalizedly seriously chap.Eczema occurring changes.Hemorrhagic occurring chaps.

Peeling begins to disappear on a large scale.

Forearm contrast coating test (FCAT) generally only is gentle to the moderate zest to skin; But in process of the test,, should end the processing at this tested position of measured any time if tested position reaches 5.0 or more high-grade.

Data

After the evaluation test end to all measured, determine following numerical value:

Rc _o=rank the meansigma methods at the tested position of reference product when initial

Rc _fThe rank meansigma methods at the tested position of reference product during=off-test

Rt _o=rank the meansigma methods at the tested position of test product when initial

Rt _fThe rank meansigma methods at the tested position of test product during=off-test

Many external conditions can influence forearm contrast coating test (FCAT), as relative humidity and hardness of water.This test is just effective when only can be observed enough dermoreactions by reference product.Control reaction should be greater than 1.0 (that is Rc, _f-Rc _o〉=1.0) test is just effective the time.

For efficiency test, what the mildness index of product was a skin to two kinds of products reactions is poor.

Mildness index=(Rc _f-Rc _o)-(Rt _f-Rt _o) agent of lipophile skin moisturizing denseness (k) and shear index (n)

Adopt Carrimed CSL100 controlled stress rheometer measurement to be applicable to this lipophile skin moisturizing agent shearing index n and denseness k.Adopt 2 ° of cones of 4cm to measure system (51 microns gaps are generally arranged) down at 35 ℃, measure by certain time dependent shear stress scheme (being generally 0.06-5,000 dynes/cm).If stress causes sample deformation, i.e. the strain of measurement geometry is at least the 10-4 radian per second, and then strained speed is called shear rate.These data are used to do the flow curve of the viscosity (μ) of material with respect to shear rate γ '.This flow curve can be through modelling to form the mathematic(al) representation of the characteristic of described composition under specific shear stress and shear rate.These results satisfy the model (for example referring to " Chemical Engineering ", Coulson and Richardson, Pergamon work, 1982 or " transfer phenomena ", Bird, Stewart and Lightfoot, Wiely work, 1960) of following generally accepted power law:

Viscosity, mu=k (γ ') ^N-1The viscosity of leave-on antimicrobial compositons

Adopt the viscosity of Wells-Brookfield awl/plate DV-II+ type viscometer determining leave-on antimicrobial compositons of the present invention.Under 25 ℃, adopt 2.4cm ° of cone (rotor CP-41) mensuration system to measure, the gap between two little points on each awl and the plate is 0.013mm.Inject the 0.5ml sample and be used for analyzing between awl and plate, the cone speed setting is 1rpm.Cone rotary resistance meeting forms torque, and torque is directly proportional with shear stress to liquor sample.Read and write down torque value (in centipoise (mPa)) by viscometer according to geometric constant, rotating speed and the torque relevant of cone with stress.

Embodiment

Adopt following examples explanation and describe the interior specific embodiments of the scope of the invention.In following examples, listed all the components is all in active matter content.Embodiment only is used for explanation, the present invention is not constituted any qualification, has multiple version under the condition that does not deviate from spirit and scope of the invention.

Composition is chemical name or CTFA name.Leave-on antimicrobial compositons

Component	Example 1	Example 2	Example 3	Example 4	Example 5
Component	Example 1	Example 2	Example 3	Example 4	Example 5	Mineral oil	??1.00％	??1.00％	??1.00％	??1.00％	??0.00％
Propylene glycol	??1.00％	??1.00％	??1.00％	??1.00％	??1.00％	Mineral oil	??1.00％	??1.00％	??1.00％	??1.00％	??0.00％
Propylene glycol	??1.00％	??1.00％	??1.00％	??1.00％	??1.00％	Ammonium lauryl sulfate	??0.60％	??0.60％	??0.60％	??0.60％	??0.60％
Citric acid	??4.00％	??0.00％	??0.00％	??0.00％	??0.00％	Ammonium lauryl sulfate	??0.60％	??0.60％	??0.60％	??0.60％	??0.60％
Citric acid	??4.00％	??0.00％	??0.00％	??0.00％	??0.00％	Sodium citrate	??3.30％	??0.00％	??2.00％	??0.00％	??0.00％
Succinic acid	??0.00％	??4.00％	??0.00％	??0.00％	??4.00％	Sodium citrate	??3.30％	??0.00％	??2.00％	??0.00％	??0.00％
Succinic acid	??0.00％	??4.00％	??0.00％	??0.00％	??4.00％	Sodium succinate	??0.00％	??3.30％	??0.00％	??0.00％	??3.20％
Malic acid	??0.00％	??0.00％	??2.50％	??0.00％	??0.00％	Sodium succinate	??0.00％	??3.30％	??0.00％	??0.00％	??3.20％
Malic acid	??0.00％	??0.00％	??2.50％	??0.00％	??0.00％	Malonic acid	??0.00％	??0.00％	??0.00％	??4.00％	??0.00％
Sodium malonate	??0.00％	??0.00％	??0.00％	??3.20％	??0.00％	Malonic acid	??0.00％	??0.00％	??0.00％	??4.00％	??0.00％
Sodium malonate	??0.00％	??0.00％	??0.00％	??3.20％	??0.00％	Steareth?20	??0.55％	??0.55％	??0.55％	??0.55％	??0.00％
Steareth?2	??0.45％	??0.45％	??0.45％	??0.45％	??0.00％	Steareth?20	??0.55％	??0.55％	??0.55％	??0.55％	??0.00％
Steareth?2	??0.45％	??0.45％	??0.45％	??0.45％	??0.00％	Triclosan 	??0.15％	??0.15％	??0.15％	??0.15％	??0.15％
Other	??0.36％	??0.36％	??0.36％	??0.36％	??0.36％	Triclosan 	??0.15％	??0.15％	??0.15％	??0.15％	??0.15％
Other	??0.36％	??0.36％	??0.36％	??0.36％	??0.36％	Water	In right amount	In right amount	In right amount	In right amount	In right amount
PH	??4.0	??4.5	??3.9	??3.9	??3.9	Water	In right amount	In right amount	In right amount	In right amount	In right amount
PH	??4.0	??4.5	??3.9	??3.9	??3.9	The microcytotoxicity of anion surfactant	??1	??1	??1	??1	??1
The end group size of anion surfactant	Little	Little	Little	Little	Little	The microcytotoxicity of anion surfactant	??1	??1	??1	??1	??1
The end group size of anion surfactant	Little	Little	Little	Little	Little	The backbone length of anion surfactant	??12	??12	??12	??12	??12

Component	Example 6	Example 7	Example 8	Example 9	Example 10	Example 10a
Component	Example 6	Example 7	Example 8	Example 9	Example 10	Example 10a	Mineral oil	0.00％	0.00％	1.00％	1.00％	1.00％	1.00％
Propylene glycol	1.00％	1.00％	1.00％	1.00％	1.00％	1.00％	Mineral oil	0.00％	0.00％	1.00％	1.00％	1.00％	1.00％
Propylene glycol	1.00％	1.00％	1.00％	1.00％	1.00％	1.00％	Ammonium lauryl sulfate	0.60％	0.60％	0.60％	0.60％	1.00％	0.60％
Citric acid	0.00％	0.00％	2.50％	2.50％	4.00％	0.00％	Ammonium lauryl sulfate	0.60％	0.60％	0.60％	0.60％	1.00％	0.60％
Citric acid	0.00％	0.00％	2.50％	2.50％	4.00％	0.00％	Sodium citrate	0.00％	3.70％	2.00％	2.00％	3.20％	0.00％
Succinic acid	4.00％	0.00％	0.00％	0.00％	0.00％	0.00％	Sodium citrate	0.00％	3.70％	2.00％	2.00％	3.20％	0.00％
Succinic acid	4.00％	0.00％	0.00％	0.00％	0.00％	0.00％	Sodium succinate	3.00％	0.00％	0.00％	0.00％	0.00％	0.00％
Malic acid	0.00％	4.00％	0.00％	0.00％	0.00％	0.00％	Sodium succinate	3.00％	0.00％	0.00％	0.00％	0.00％	0.00％
Malic acid	0.00％	4.00％	0.00％	0.00％	0.00％	0.00％	The poly propenoic acid sodium acrylate ^*	0.00％	0.00％	0.00％	0.00％	0.00％	2.5％
Steareth?20	0.55％	0.00％	0.55％	0.08％	0.28％	0.08％	The poly propenoic acid sodium acrylate ^*	0.00％	0.00％	0.00％	0.00％	0.00％	2.5％
Steareth?20	0.55％	0.00％	0.55％	0.08％	0.28％	0.08％	Steareth?2	0.45％	0.00％	0.45％	0.07％	0.23％	0.07％
Oleth?20	0.00％	0.00％	0.00％	0.08％	0.28％	0.08％	Steareth?2	0.45％	0.00％	0.45％	0.07％	0.23％	0.07％
Oleth?20	0.00％	0.00％	0.00％	0.08％	0.28％	0.08％	Oleth?2	0.00％	0.00％	0.00％	0.07％	0.23％	0.07％
Triclosan 	0.00％	0.50％	0.50％	0.15％	0.25％	0.15％	Oleth?2	0.00％	0.00％	0.00％	0.07％	0.23％	0.07％
Triclosan 	0.00％	0.50％	0.50％	0.15％	0.25％	0.15％	Thymol	1.00％	0.00％	0.00％	0.00％	0.00％	0.00％
Other	0.36％	0.36％	0.36％	0.36％	0.36％	0.36％	Thymol	1.00％	0.00％	0.00％	0.00％	0.00％	0.00％
Other	0.36％	0.36％	0.36％	0.36％	0.36％	0.36％	Water	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount
PH	3.2	5.0	3.9	3.9	3.9	3.8	Water	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount
PH	3.2	5.0	3.9	3.9	3.9	3.8	The microcytotoxicity of anion surfactant	1	1	1	1	1	1
The end group size of anion surfactant	Little	Little	Little	Little	Little	Little	The microcytotoxicity of anion surfactant	1	1	1	1	1	1
The end group size of anion surfactant	Little	Little	Little	Little	Little	Little	The backbone length of anion surfactant	12	12	12	12	12	12

^*Rohm ﹠amp; The Acumer 1020 that Hass company sells

Component	Example 11	Example 12	Example 13	Example 14	Example 15
Component	Example 11	Example 12	Example 13	Example 14	Example 15	Mineral oil	??1.00％	??1.00％	??1.00％	??1.00％	??1.00％
Propylene glycol	??1.00％	??1.00％	??1.00％	??1.00％	??1.00％	Mineral oil	??1.00％	??1.00％	??1.00％	??1.00％	??1.00％
Propylene glycol	??1.00％	??1.00％	??1.00％	??1.00％	??1.00％	Ammonium lauryl sulfate	??0.00％	??0.00％	??0.00％	??0.00％	??0.60％
Zetesol AP	??0.00％	??5.00％	??0.00％	??0.00％	??0.00％	Ammonium lauryl sulfate	??0.00％	??0.00％	??0.00％	??0.00％	??0.60％
Zetesol AP	??0.00％	??5.00％	??0.00％	??0.00％	??0.00％	Hostapur?SAS60(SPS)	??1.00％	??0.00％	??0.00％	??0.00％	??0.00％
C14-C16 alhpa olefin sodium sulfonate	??0.00％	??0.00％	??2.00％	??0.00％	??0.00％	Hostapur?SAS60(SPS)	??1.00％	??0.00％	??0.00％	??0.00％	??0.00％
C14-C16 alhpa olefin sodium sulfonate	??0.00％	??0.00％	??2.00％	??0.00％	??0.00％	Sodium N-lauroyl sarcosinate	??0.00％	??0.00％	??0.00％	??1.00％	??0.00％
Citric acid	??0.055％	??7.50％	??0.00％	??0.00％	??0.00％	Sodium N-lauroyl sarcosinate	??0.00％	??0.00％	??0.00％	??1.00％	??0.00％
Citric acid	??0.055％	??7.50％	??0.00％	??0.00％	??0.00％	Sodium citrate	??0.00％	??4.00％	??2.00％	??0.00％	??0.00％
Succinic acid	??4.00％	??0.00％	??0.00％	??0.00％	??0.00％	Sodium citrate	??0.00％	??4.00％	??2.00％	??0.00％	??0.00％
Succinic acid	??4.00％	??0.00％	??0.00％	??0.00％	??0.00％	Sodium succinate	??0.67％	??0.00％	??0.00％	??0.00％	??0.00％
Malic acid	??0.00％	??0.00％	??2.50％	??0.00％	??0.00％	Sodium succinate	??0.67％	??0.00％	??0.00％	??0.00％	??0.00％
Malic acid	??0.00％	??0.00％	??2.50％	??0.00％	??0.00％	Malonic acid	??0.00％	??0.00％	??0.00％	??4.00％	??0.00％
Sodium malonate	??0.00％	??0.00％	??0.00％	??3.20％	??0.00％	Malonic acid	??0.00％	??0.00％	??0.00％	??4.00％	??0.00％
Sodium malonate	??0.00％	??0.00％	??0.00％	??3.20％	??0.00％	Salicylic acid	??0.00％	??0.00％	??0.00％	??0.00％	??0.50％
Steareth?20	??0.55％	??0.55％	??0.55％	??0.55％	??0.55％	Salicylic acid	??0.00％	??0.00％	??0.00％	??0.00％	??0.50％
Steareth?20	??0.55％	??0.55％	??0.55％	??0.55％	??0.55％	Steareth?2	??0.45％	??0.45％	??0.45％	??0.45％	??0.45％
Triclosan 	??0.15％	??3.00％	??0.15％	??0.01％	??0.15％	Steareth?2	??0.45％	??0.45％	??0.45％	??0.45％	??0.45％
Triclosan 	??0.15％	??3.00％	??0.15％	??0.01％	??0.15％	Cocamido propyl betaine	??0.00％	??0.00％	??0.00％	??4.00％	??0.00％
Polyquaternary ammonium salt 10	??0.00％	??0.00％	??0.00％	??0.40％	??0.00％	Cocamido propyl betaine	??0.00％	??0.00％	??0.00％	??4.00％	??0.00％
Polyquaternary ammonium salt 10	??0.00％	??0.00％	??0.00％	??0.40％	??0.00％	Other	??0.36％	??0.36％	??0.36％	??0.36％	??0.36％
Water	In right amount	In right amount	In right amount	In right amount	In right amount	Other	??0.36％	??0.36％	??0.36％	??0.36％	??0.36％
Water	In right amount	In right amount	In right amount	In right amount	In right amount	PH	??3-6	??3-6	??3-6	??3-6	??3-6
The microcytotoxicity of anion surfactant	??n/a	??150	??20	??＜150	??1	PH	??3-6	??3-6	??3-6	??3-6	??3-6
The microcytotoxicity of anion surfactant	??n/a	??150	??20	??＜150	??1	The end group size of anion surfactant	Little	Greatly	Little	Greatly	Little
The backbone length of anion surfactant	??15.5	??12	??14-16	??12	??12	The end group size of anion surfactant	Little	Greatly	Little	Greatly	Little

Shown leave-on antimicrobial compositons all has the anti-gram negative bacteria time-delay effect index greater than about 0.3, resisting gram-positive bacteria time-delay effect index greater than 0.5, the instant bactericidal index of once cleaning greater than about 1.0 and greater than 0.3 mildness index.The step of preparation leave-on antimicrobial compositons example

When using mineral oil, premix mineral oil, propylene glycol, activating agent, steareth 2 and 20, oleth 2 and 20 and account for the water of oil, glycol, activating agent, steareth and oleth substance weight 50% in a pre-mix reservoir earlier.Be heated to 165 °F ± 10 °F.In pre-mix reservoir, add the water that accounts for oil, glycol, activating agent, steareth and oleth substance weight 50% again.

All all the other water except that 5% are joined in second blending tank.In blending tank, add pre-composition on demand.In blending tank, add surfactant.Material is heated to 155 °F ± 10 °F, mixes until dissolving.Be cooled to and be lower than 100 °F, add acid and antimicrobial activities, in premix, and essence.Mixing is dissolved fully until material.With required buffer agent (NaOH or buffer salt) pH regulator is arrived desired value.Add remaining water and obtain finished product.

Claims

1. leave-on antimicrobial compositons is characterized in that wherein containing:

(a) 0.001-5% antimicrobial acivity composition;

(b) 0.05-10% anion surfactant;

(c) 0.1-10% gives proton reagent; With

(d) 0-99.85% water;

Wherein the pH regulator of compositions is to 3.0-6.0;

The gram negative bacteria time-delay antibiotic effect index of this leave-on antimicrobial compositons is greater than 0.5;

The mildness index of this leave-on antimicrobial compositons is greater than 0.3.

2. leave-on antimicrobial compositons is characterized in that wherein containing:

(a) 0.001-5% antimicrobial acivity composition;

(b) 0.05-10% anion surfactant;

(c) 0.1-10% gives proton reagent; With

(d) 0-99.85% water;

Wherein the pH regulator of compositions is to 3.0-6.0;

The gram positive bacteria time-delay antibiotic effect index of this leave-on antimicrobial compositons is greater than 0.5;

3. leave-on antimicrobial compositons is characterized in that it can effectively kill gram positive bacteria, gram negative bacteria, fungus, yeast, mycete and virus, contains in the compositions:

(a) 0.001-5% antimicrobial acivity composition;

(b) 0.05-10% anion surfactant;

(c) 0.1-10% gives proton reagent; With

(d) 0-99.85% water;

Wherein the pH regulator of compositions is to 3.0-6.0;

The once cleaning of said composition is sterilized index immediately greater than 1.0, and

4. each described leave-on antimicrobial compositons during aforesaid right requires, wherein the antimicrobial acivity composition is selected from triclosan , triclocarban , Octopirox, PCMX, ZPT, natural essential oil and main component thereof and their mixture.

5. each described leave-on antimicrobial compositons during aforesaid right requires, wherein the microcytotoxicity index of anion surfactant is less than 150.

6. each described leave-on antimicrobial compositons during aforesaid right requires, wherein anion surfactant is selected from: chain length is mainly alkyl sodium sulfate, alkylsurfuric acid ammonium and sodium alkylether sulphate, the alkyl ether ammonium sulfate of 12-14 carbon atom, chain length is mainly the olefin sulphates of 14-16 carbon atom, average chain length is the alkane sulfonate of 13-17 carbon atom and their mixture.

7. each described leave-on antimicrobial compositons during aforesaid right requires is a buffer capacity greater than 0.005 organic acid to proton reagent wherein.

8. each described leave-on antimicrobial compositons during aforesaid right requires is wherein to proton reagent select oneself diacid, tartaric acid, citric acid, maleic acid, malic acid, succinic acid, glycolic, 1,3-propanedicarboxylic acid, benzoic acid, malonic acid, salicylic acid, gluconic acid, polyacrylic acid, their salt and their mixture.

9. each described leave-on antimicrobial compositons among the claim 1-5 is a mineral acid to proton reagent wherein.

10. each described leave-on antimicrobial compositons during aforesaid right requires, the amount ratio of wherein non-anion surfactant and anion surfactant is lower than 1: 1.

11. each described leave-on antimicrobial compositons during aforesaid right requires further comprises 0.2% to 10% lipophile skin moisturizing agent.

12. one kind provides the method to gram negative bacteria time-delay antibiotic effect, comprising the compositions described in above-mentioned arbitrary claim of using safe and effective amount on human body skin.

13. a method of handling acne is comprising the compositions described in above-mentioned arbitrary claim of using safe and effective amount on human body skin.