CN1329500A - Anti-dandruff composition comprising antifungal polypeptide - Google Patents

Anti-dandruff composition comprising antifungal polypeptide Download PDF

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CN1329500A
CN1329500A CN99813927A CN99813927A CN1329500A CN 1329500 A CN1329500 A CN 1329500A CN 99813927 A CN99813927 A CN 99813927A CN 99813927 A CN99813927 A CN 99813927A CN 1329500 A CN1329500 A CN 1329500A
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compositions
polypeptide
fungus
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surfactant
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J·文德
N·H·索伦森
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Novozymes AS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
    • C07K14/38—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from Aspergillus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/70—Biological properties of the composition as a whole

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Abstract

The present invention relates to an anti-dandruff composition comprising an antifungal polypeptide, to the use of an antifungal polypeptide for the treatment or prophylaxis of dandruff, to a method for the treatment or prophylaxis of dandruff, and to the use of an antifungal polypeptide for the preparation of a composition for the treatment or prophylaxis of dandruff. It has been found that the antifungal polypeptide with the amino acid sequence shown in Fig. 1 efficiently impedes the growth of the yeast P. ovale, even in low concentrations.

Description

The anti-dandruff composition that contains anti-fungus polypeptide
Invention field
The present invention relates to contain the anti-dandruff composition of anti-fungus polypeptide, anti-fungus polypeptide application in the dandruff in treatment or prevention, the method for treatment or prevention dandruff and antidandruff polypeptide are used for the treatment of or prevent application in the compositions of dandruff in preparation.
Background of invention
Dandruff is that the scalp functional disorder causes, but it does not think dermatosis, and therefore, dandruff should be with stage and its similar disease make a distinction in early days.Although dandruff is a kind of cosmetic problem, still carried out a large amount of research for the field of this symptom of treatment.
Extensively approval is, dandruff is caused by yeast pityrosporum ovale (Pityrosporum ovale) that mainly therefore, the material that suppresses the pityrosporum ovale growth may be useful in treatment or prevention dandruff.
The active substance that is used for the treatment of dandruff traditionally comprises for example various coal tar goods, salicylic acid, selenium sulfide and two (oxidation of 2-mercaptopyridine) zinc.
Recently, WO 95/27471 has described a kind of new antidandruff shampoo that contains ketoconazole or elubiol.
Yet some have very undesirable abnormal smells from the patient in the existing material, and other are the very strong materials that are applied under medical treatment guidance and control only on the scalp.Therefore, be necessary to develop easy production (as by microorganism), do not produce offending abnormal smells from the patient again, and be not harmful to the material of character.
Summary of the present invention
Find surprisingly, even have the anti-fungus polypeptide of aminoacid sequence shown in Figure 1 also can effectively stop pityrosporum ovale under low concentration growth.
Therefore, in first aspect, the present invention relates to be fit to be applied to people's the hair or the anti-dandruff composition of scalp, it comprises the anti-fungus polypeptide with the shown aminoacid sequence of Fig. 1 or its variant of effective dose, and described variant is
I) can with the polypeptide of following antibody response, described antibody can with at least one epi-position reaction of polypeptide with aminoacid sequence shown in Figure 1, or
II) the homologous substantially polypeptide of its aminoacid sequence and amino acid sequence of polypeptide shown in Figure 1.
In second aspect, the present invention relates to the application of anti-fungus polypeptide in treatment or prevention dandruff of above definition.
In the third aspect, the present invention relates to treat or prevent the method for dandruff, described method comprises the anti-fungus polypeptide contact hair with the above definition of effective dose.
At last, the anti-fungus polypeptide that the invention still further relates to above definition is used for the treatment of or prevents application in the compositions of dandruff in preparation.
Brief description of drawings
Fig. 1 shows the full length amino acid sequence of anti-fungus polypeptide of the present invention.
Fig. 2 is the sketch map of microtitration plate of yeast pityrosporum ovale of having grown, referring to embodiment 1.
Detailed description of the present invention is described anti-fungus polypeptide and variant thereof
In this article, use amino acid whose three-letter code by its traditional sense.Unless spell out, aminoacid mentioned in this article is L type aminoacid.
Predicate used herein " anti-fungus polypeptide " is intended to comprise the linearity and the active foldable structure of described polypeptide, and, in suitable place, can and predicate " antifungal protein " exchange to use.
Be meant polypeptide or the naturally occurring variant that polypeptide with aminoacid sequence shown in Figure 1 derives with the predicate " variant " of anti-fungus polypeptide coupling.Typically, this variant has one or more amino acid residues different with natural anti-fungus polypeptide, these one or more amino acid residues can insert or disappearance from the one or both ends of described polypeptide N-terminal or C-terminal, also can insert or disappearance in the one or more sites of described polypeptid acid sequence inside, or in described polypeptid acid sequence inside or one or both ends substituted by one or more amino acid residues.
And variant of the present invention has above-mentioned characteristic I) and II) one or two.
Characteristic I), the reactivity of variant promptly of the present invention and following antibody, wherein said antibody is anti-to have hereinafter at least one epi-position or the reaction with it of the polypeptide of aminoacid sequence shown in Figure 1.This characteristic can be used by the antibody preparation of the preparation of the description in hereinafter material and the method division header " preparation of anti-AFPP antibody " and measure.Antibody response can adopt methods known in the art to measure, and described method is Western trace or radially immunodiffusion analysis for example, for example 1989 described methods such as Hudson.
AFPP homology mentioned above is determined by the degree of consistency between second deutero-two protein sequence of sequence with first sequence of demonstration.This homology can suitably be determined by computer program known in the art, as the GAP (procedure manual of Wisconsin program package (Program Manual for the Wisconsin Package) that provides in the GCG program package, the 8th edition, in August, 1994, Genetics Computer Group, 575 Science Drive, Madison, Wisconsin, USA 53711) (Needleman, S.B. and Wunsch, C.D., (1970), molecular biology magazine (Journal of Molecular Biology), 48, the 443-453 pages).Use vacancy (Gap) and the following setting that is used for the peptide sequence comparison: vacancy is set up point penalty 3.0, vacancy is extended point penalty 0.1, the maturing part of the polypeptide of similar DNA sequential coding of the present invention shows and the maturing part of aminoacid sequence shown in Figure 1 has preferably at least about 60%, as at least about 70%, at least about 80%, at least about 90%, at least about 95%, more preferably at least about 97%, most preferably at least about 99% the degree of consistency.
Preferably, AFPP comprises the aminoacid sequence of Fig. 1; Or its allelic variant; Or it has the active fragment of AFPP.
The fragment of AFPP is to have one or more amino acid whose polypeptide that are selected from this aminoacid sequence amino and/or carboxyl terminal.Allelic variant is meant that a gene is positioned at any one of two or more alternative forms of identical chromosomal loci.Allelic variation can cause the polymorphism of population inside by the natural generation of sudden change.Gene mutation can be reticent (coded protein not change), the polypeptide of the aminoacid sequence with change of also can encoding.The allelic variant of polypeptide is an allele variant encoded polypeptide.
The aminoacid sequence of homology AFPP and the aminoacid sequence of Fig. 1 different can be the insertion of one or more amino acid residues or disappearance and/or substitute one or more amino acid residues by different amino acid residues.Preferably, amino acid change is smaller in nature, promptly is that not appreciable impact protein folding and/or active conserved amino acid substitute; Little disappearance, the typical case is 1 to about 30 amino acid whose disappearances; Little amino or carboxyl terminal are outstanding, as aminoterminal methionine residues; Be no more than the little joint peptide of about 20-25 residues; Be convenient to the little outstanding of purification by changing net charge or other function, as polyhistidyl fragment, epitope or in conjunction with the territory.
Predicate used herein " effective dose " is meant the anti-fungus polypeptide with aminoacid sequence shown in Figure 1 or the amount of its variant, and this amount is enough to control (thereby remove or be restriction at least) because the peeling that dandruff causes.
Typically, according to polypeptide used in the present invention from microorganism.Can produce by other microorganism such as antibacterial, protozoacide and algae although can imagine anti-fungus polypeptide or its variant, this polypeptide is usually from fungus, particularly the fungus of aspergillus (Aspergillus).
Described in detail as WO 94/01459, in being, some strains of the huge aspergillosis of fungus kind (A.giganteus) found to have the anti-fungus polypeptide of aminoacid sequence shown in Figure 1, an example of described strain system be at fungus strain preservation center (Centraallbureauvoor Schimmelcultures, CBS) preservation, preserving number is the huge aspergillosis strain of CBS 526.65.
But, be suitable for to expect from other fungus kind according to anti-fungus polypeptide or its variant of application of the present invention, other aspergillus species particularly, as A.pallidus, excellent aspergillosis (A.clavatus), A.longivesica, A.rhizopodus and A.clavatonanicus, because there is the relation of nearly edge between these kinds and the huge aspergillosis.
As mentioned above, the variant of anti-fungus polypeptide can be the variant of natural origin, i.e. the isolating polypeptide of enumerating more than any of fungus kind also can be based on the aminoacid sequence knowledge architecture, the synthetic variant that produces of anti-fungus polypeptide.
As mentioned before, other variant of anti-fungus polypeptide also can be used for purpose of the present invention.Therefore, can consider, use technology known in the art, as NMR (as protein engineering (ProteinEngineering), editor Oxender, D.L. and Fox, C.F., Alan R.Liss, Inc.New York (1987) is described), X-ray diffraction, computer simulation etc., according to analysis to the conformational structure and the avtive spot of anti-fungus polypeptide shown in Figure 1, can identify polypeptide shown in Figure 1 useful, also can be used for treating or the variant of anti-antidandruff.When having identified the one or more interesting change of anti-fungus polypeptide aminoacid sequence, can prepare corresponding variant by the encode nucleotide sequence of this anti-fungus polypeptide of suitable modification.
Before, Nakaya etc. (1990) disclosed the aminoacid sequence of huge aspergillosis anti-fungus polypeptide.Wnendt etc. (1990) have described corresponding cDNA sequence, and WO 91/19738 has described the application of this cDNA sequence in making up the transgenic plant that can produce this polypeptide.Among the embodiment that this paper provides among used anti-fungus polypeptide (anti-fungus polypeptide that promptly has aminoacid sequence shown in Figure 1) and the WO 91/19738 disclosed anti-fungus polypeptide have following different:
Asn-4 is substituted by Pro, and Ala-24 is substituted by Gly, and Lys-32 is substituted by Arg, and Phe-42 is substituted by Leu, and Tyr-50 is substituted by His.
Therefore, polypeptide shown in Figure 1 is used for the treatment of or prevents an object lesson of the interesting variant of dandruff is to comprise aminoacid sequence shown in Figure 1, the preferred anti-fungus polypeptide of forming by this sequence, wherein the 4th Pro substitutes with Asn, the 24th Gly substitutes with Ala, the 32nd Arg substitutes with Lys, and the 42nd Leu substitutes with Phe, and/or the 50th His substitutes with Tyr.
Another interesting variant is disclosed in WO 94/01459.WO 94/01459 disclosed aminoacid sequence has following different with aminoacid sequence shown in Figure 1:
Pro-4 is substituted by Asp, and Gly-24 is substituted by Ala, and Arg-32 is substituted by Val, and Leu-42 is substituted by Phe, and His-50 is substituted by Tyr.
Therefore, polypeptide shown in Figure 1 is used for the treatment of or prevents another object lesson of the interesting variant of dandruff is to comprise aminoacid sequence shown in Figure 1, the preferred anti-fungus polypeptide of forming by this sequence, wherein the 4th Pro substitutes with Asp, the 24th Gly substitutes with Ala, the 32nd Arg substitutes with Val, and the 42nd Leu substitutes with Phe, and/or the 50th His substitutes with Tyr.
Yet, it is contemplated that except that above-mentioned those, other variant also may be useful in the treatment of dandruff or prevention.Therefore, one or more amino acid residues that anti-fungus polypeptide shown in Figure 1 is the 4th, 24,32,42 and 50 substituted by other naturally occurring amino acid residue these variants produced according to application of the present invention, be also included within the scope of the present invention.
Anti-fungus polypeptide shown in Figure 1 and variant thereof can prepare by methods known in the art.Provided the detailed description of the preparation of polypeptide shown in Figure 1 among the WO 94/01459.Anti-dandruff composition
Although for easy, compositions described herein is commonly called " shampoo Compositions ", it will be understood by those skilled in the art that described anti-fungus polypeptide also can be incorporated into to be fit to be applied in any other compositions of scalp or hair.Therefore, the non-shampoo Compositions of this class that comprises described anti-fungus polypeptide is also included within the scope of the present invention.The example of these other compositionss is solution, suspension, emulsion, gel, foam, paste etc.Therefore, although shampoo is a present preferred composition of using anti-fungus polypeptide of the present invention, but it is contemplated that, also can use this anti-fungus polypeptide, for example be mixed with hair gel or mousse, hair lotion, hair spray, hair conditioner, hair finishing agent etc. by other means.
Can make shampoo Compositions be fit to oiliness, dryness or normal hair, and can be by mode well known to those skilled in the art, as " WoodruffShi composition and formulary (Woodruff ' singredients﹠amp; Formulary handbook) ", 1997, the mode described in the Miller Freeman, preparation shampoo Compositions.Equally, hair gel or mousse, hair lotion, hair spray, hair conditioner etc. also can use to be used to prepare the composition known in the art and the method that are fit to be applied to this compositions on hair or the scalp and to prepare.Yet, it will be apparent to one skilled in the art that according to anti-dandruff composition of the present invention should not adopt may the inactivation anti-fungus polypeptide composition or method (as too high temperature).
Active component promptly contains anti-fungus polypeptide or its variant of aminoacid sequence shown in Figure 1, uses with the amount that can effectively treat or prevent dandruff at shampoo Compositions.
Typically, shampoo Compositions of the present invention contains based on about 10 of this shampoo Compositions total weight -7Anti-fungus polypeptide to about 10% weight.The amount of preferred anti-fungus polypeptide is about 5 * 10 -6In about 5% scope, in office one following subrange: about 5 * 10 -6To about 0.5%; About 5 * 10 -6To about 0.1%; About 5 * 10 -6To about 10 -5%; About 10 -5To about 10 -4%; About 10 -4To about 10 -3%; About 10 -3To about 0.01%; About 0.01 to about 0.1%; About 0.1% to about 1.0%; With about 1.0% to about 5.0%.
Can contain main one or more surfactants according to shampoo Compositions of the present invention as cleaning agent.Suitably the selection of surfactant is the common sense problem to those skilled in the art.Usually in shampoo Compositions, use anion surfactant.This examples of anionic surfactants is alkylsurfuric acid, alkyl benzene sulphonate, alkyl sulfone, alpha-olefins base sulfonic acid, polyoxyethylene alkylphenyl sulfonic acid and the vitriolic alkali metal of polyoxyethylene alkylphenyl, ammonium or hydroxyalkyl amine salt.Also can use surfactant mixtures.
An object lesson that can be included in according to the suitable surfactant in the shampoo Compositions of the present invention is a sodium laureth sulfate, and its molecular formula is CH 3(CH 2) 10CH 2(OCH 2CH 2) nOSO 3Na, wherein the n representative has the numeral of 1-4 meansigma methods.
Another object lesson that can be incorporated into the suitable surfactant in the shampoo Compositions of the present invention is the cocoyl sodium sarcosinate.The cocoyl sarcosine is the coco-nut oil fatty acid amide of sarcosine (sarcosine), and coconut fatty acid is myristic acid, lauric acid, Palmic acid and stearic mixture.
Other object lesson that can be incorporated into the suitable surfactant in the shampoo Compositions of the present invention comprises C 14, C 15And C 16Ethylenic sodium sulfonate, sodium lauryl sulphate, cocamidopropyl propyl amide amine oxide, lauramide diethanolamine (1auramido diethanolamine) (lauramide DEA), cocamidopropyl betaine, oleamide MIPA sulfo-succinic acid disodium, coconut oleoyl amine MIPA sulfo-succinic acid disodium, lauryl ether sulfo-succinic acid disodium, cocos nucifera oil acyl both sexes carboxyl glycinates (cocoaamphocarboxy-glycinate) and MEA sulfo-succinic acid disodium.
The another kind of interesting surfactant that can add in the present composition is a sugar surfactant.The example of the surfactant of sugar surfactant form comprises (a) alkyl and/or alkenyl poly glucoside and/or (b) fatty acid N-alkyl polyhydroxy alkylamide.
Alkyl and/or alkenyl poly glucoside (a) can have following molecular formula (I)
R 1-O-[G] p(I) R wherein 1=C 4-22Alkyl and/or alkenyl, G=have the saccharide residue of 5 or 6 carbon atoms, p=1-10.
Fatty acid N-alkyl polyhydroxy alkylamide (b) can have following molecular formula:
R 2CO-N(R 3)-[Z]????????(II)
R wherein 2CO=C 6-22The aliphatic acyl residue, R 3=H, alkyl or hydroxyalkyl with 1-4 carbon atom, the linear or ramose polyhydroxyalkyl residue of [Z]=have 3-12 carbon atom and 3-10 OH base.
It comprises that also a) molecular formula is R 1-O-[G] pAlkyl and alkenyl poly glucoside and b) C 12-22Secondary 2, the alkali of 3-alkylsurfuric acid and/or alkali metal salt, wherein R 1=C 4-22Alkyl and/or alkenyl; G=has the saccharide residue of 5 or 6 carbon atoms, p=1-10.(I): weight ratio (II) preferred 1: 99-99: 1.
Also comprise fatty acid N-alkyl polyhydroxy alkylamide; And sugar surfactant: sucrose ester, sorbitan ester and/or polysorbate.
It is R that sugar surfactant also can comprise the molecular formula that 10-40% calculates by weight 1-O-[G] pAlkyl and/or the molecular formula calculated by weight of alkenyl poly glucoside, 10-40% be R 2-O-(G) pAlkyl and/or the molecular formula calculated by weight of alkenyl poly glucoside and 80-20% be R 3-(OCH 2CH 2) nO-SO 3The alkyl ether sulfate of M, wherein R 1=C 8-11Alkyl or alkenyl; (G)=glucosyl group; P=1-10, preferred 1-3; R 2=C 12-22Alkyl or alkenyl; R 3=C 6-22Alkyl or alkenyl; M=alkali or alkaline-earth metal, or ammonium or alkanol ammonium ion, preferred Na or Mg; N=1-20, preferred 2-7.Preferably, R 2And R 3Be C independently 12-14Alkyl.
Another example of sugar surfactant is polyglyceryl fatty acid ester polyoxyalkylene ether R 1R 2R 3N +-CH (Y)-CH 2-O-CH 2-C (CH 3) 2-C (OH) (H)-C (=O)-NH-CH 2-CH 2-OHX -(I), R wherein 1, R 2=C 1-24Alkyl or C 8-24Alkenyl; R 3=C 1-18Alkylidene; X -=unit price organic or inorganic anion; Y=OH or H.
Sugar surfactant also can comprise the polyol moiety ester that fatty alcohol polyglycol ether that (A) 1-5% calculates by weight, the pure and mild 1-5% of Guerbet that 1-5% calculates by weight calculate by weight, (B) anionic polymer calculated by weight of 1-5%, (C) the fatty alcohol polyglycol ether sulfate calculated by weight of 15-30%, (D) alkyl polyglucoside calculated by weight of 15-30%; With molecular formula be R uCO-N (R 2The sulfating product of the fatty acid of)-Z-N-alkyl polyhydroxy alkylamide, wherein, R 1CO=C 6-22Aliphatic acyl; R 2=H, C 1-4Alkyl or C 1-4Hydroxyalkyl; Z=contains the C of 3-10 hydroxyl 3-12Polyhydroxy alkyl.
Sugar surfactant also can be selected from the alkyl polyglucoside of molecular formula (I) and the carboxylic acid N-polyhydroxy alkyl amide of molecular formula (II):
R 1-O(G)????????????????????(I)
R 2CO-NR 3-Z (II) is R wherein 1=optional hydroxylation C 1-8Alkyl; G=has the saccharide residue of 5-6 carbon atom; P=1-10; R 2CO=C 1-8Aliphatic acyl; R 3=H, C 1-8Alkyl or C 1-8Hydroxyalkyl; Z=contains the C of 3-10 OH group 3-12Polyhydroxy alkyl.
Shampoo Compositions of the present invention also can comprise foaming agent such as fatty acid list or two alkanolamides, as for example coconut oleoyl amine MEA (cocamide MEA) (mixture of coconut acid single ethanol amide), coconut oleoyl amine DEA (cocamide DEA) (mixture of coconut acid diglycollic amide), oleamide DEA and oleamide DEA.
Shampoo Compositions of the present invention also can comprise one or more viscosity intensifiers so that give this shampoo suitable " denseness ".The example of this viscosity intensifier is Carbopol 1342 and cellulose derivative such as hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, carboxymethyl cellulose etc.For controlling the viscosity of final shampoo Compositions, also can add a small amount of (being generally 0.2 to 5.0% weight) NaCl.
In addition, compositions of the present invention also can comprise one or more preservative agents such as EDTA four sodium (tetrasodium ethylenediamine tetraacetate), quaternium-15 (1-(3-chlorallyl)-3,5,7-three azepines-1-nitrogen-diamantane (obsolete) chloride), Kathon CG insecticide (mixture of 5-chloro-2-methyl-4-isothiazoline-3-ketone and 2-methyl-4-isothiazoline-3-ketone), p-Hydroxybenzoate, methyl butex, benzylalcohol etc.
It will be understood by those skilled in the art that compositions of the present invention also can comprise other attached auxiliary agent such as spice, coloring agent, opacifying agent, regulator such as polyquaternium-7 (it is the polymeric quaternary ammonium salts of acrylamide and dimethyl diallyl ammonium chloride), pearling agent such as glycol distearate and ethylene glycol monostearate, antioxidant such as butylated hydroxytoluene (BHT) and butylated hydroxyanisol (BHA) and/or pH regulator agent such as citric acid, phosphoric acid, sodium hydroxide etc.
In addition, except that anti-fungus polypeptide, the present composition also can comprise the composition that one or more have therapeutic activity.It is this that the example of the composition of therapeutic activity is arranged is Octopirox (a kind of seborrheic dermatitis medicine of controlling, its chemical name are 1-hydroxy-4-methyl-6-(2,4,4-front three amyl group)-2 (1H)-pyridones), ketoconazole and elubiol.
Usually, the composition of shampoo Compositions of the present invention uses by conventional amounts, for example:
I) surfactant of 10-65%,
The ii) foaming agent of 1-10%,
The iii) viscosity intensifier of 0.1-2%,
Thereby iv) be enough to delay preservative agent and/or the antioxidant that this shampoo Compositions degraded provides long enough to shelf-life,
V) produce acid, alkali or the buffer of expected range pH (being typically 4 to 10),
Vi) add suitable quantity of water to 100%.
Provided many object lessons (anti-fungus polypeptide defined above abbreviates AFPP as in these examples) of the various shampoo Compositions that contain anti-fungus polypeptide defined above below: shampoo Compositions I (" the universal shampoo that is used for normal hair) A. water 50.00%
Sodium laureth sulfate 40.00%
Cocamidopropyl betaine 5.00%
Lauramide DEA 1.50%
AFPP 5 * 10 -6-1.0%B. citric acid 0.07%C. sodium chloride 2.50%D. spice, coloring agent is an amount of
100.00% shampoo Compositions II (" aminoacid shampoo ") A. water 30.00%B. hydroxypropyl guar gum hydroxypropyl-trimethyl ammonium chloride (Hydroxypropyl guar hydroxypropyltrimoniumchloride) 0.30%C. citric acid 0.05%D.EDTA, four sodium, 0.10% methyl butex 0.15%
PCA sodium 1.00%
Sodium laureth sulfate 30.00%
TEA-cocoyl glutamate, Glu
(TEA-cocoyl?glutamate)??????????15.00％
Cocamidopropyl betaine 9.50%
PEG-150 distearate 1.00%E. lauramide DEA 2.00%F. methylchloroisothiazandnone and Methylisothiazolinone 0.05%
Lysine hydrochloride 0.05%
Proline 0.05%
AFPP????????????????????????????5×10 -6-1.0％
Spice 0.20%
Sodium chloride 0.80%G. water is an amount of
100.00% shampoo Compositions III (" the neutral shampoo of Full-Family Ultra ") A. water 50.00%
Coloring agent (one or more) is an amount of
The PEG-80 sorbitan laurate (with)
Cocamidopropyl betaine (with)
Sodium trideceth sulfate (with)
Lauroyl both sexes sodium acetate (with)
The PEG-150 distearate (with)
Lauryl ether-13 carboxylic acid sodium (with)
Citric acid (with) Quaternium-15 (with)
EDTA four sodium (Miracare BC-10, Rhone-Poulenc) the 38.50%B. butanediol (with) water (with)
Chamomile extract (with)
Aloe barbadensis extract (with)
Balm of Gilead (Commiphora gileadensis) extract
(with) Althaea officinalis L. (Althea officinalis) extract
(Actiplex，Active?Organics)????????????????1.00％
AFPP???????????????????????????????????????5×10 -6-1.0％
Quaternium-15??????????????????????????????0.20％
The spice The addition of C. citric acid 0.10%D. sodium chloride 1.50%
Water is an amount of
100.00% shampoo Compositions IV (" Marine Poultice shampoo ") A. water 30.00%B. methyl parahydroxybenzoate 0.05%
Propyl parabene 0.15%C. ultra micro Thallus Laminariae (Thallus Eckloniae) 15.0%
Lithothamne?Lithothamne?T-450??????????????9.00％
Marine silts (Int ' l Sourcing) 5.00%D. Zetesol AP 32.50%
PEG-7 glyceryl cocoate 1.50%E. spice is an amount of
AFPP 5 * 10 -6-1.0%F. water is an amount of
100.00% shampoo Compositions V (" neutral shampoo ") A. water 50.00%B. Polyquaternium-10 0.20%C. sodium laureth sulfate, 28% activity 25.00%
Decoyl/decoyl glucoside 8.00%
Cocamidopropyl betaine, 30% activity 9.00%
AFPP 5 * 10 -6-1.0%D. PEG-120 methyl glucoside dioleate 1.50%E. sodium chloride 0.30%F. citric acid is an amount of
Preservative agent is an amount of
Spice is an amount of
Water is an amount of
100.00% shampoo Compositions VI (" nutrition hair-washing agent ") A. sodium laureth sulfate 25.00%
Preservative agent is an amount of
PEG-120 methyl glucoside dioleate 1.00%
An amount of B. Polyquaternium-11 2.00% of water
The collagen 2.00% of hydrolysis
Cocamidopropyl betaine 8.00%
Oleamide DEA 1.30%
Soluble collagen 3.00%
The lactoprotein 2.00% of hydrolysis
AFPP?????????????????????????????????????????????????5×10 -6－1.0％
100.00% shampoo Compositions VII (" the oatmeal shampoo that contains ceramide ") A. water 15.00%
Xanthan gum, 0.25% solution 30.00%B. water (with) glycerol (with) hydroxypropyl emthylcellulose (with) glucuronic acid (with) glucose (with) polyacrylic acid glycerol ester 25.00% AFPP 5 * 10 -6-1.0%C. colloidal oatmeal powder 2.00%D. coconut oleoyl amine DEA 3.00% sodium laureth sulfate 20.00% isohexadecane alcohol (with) butanediol (with) Cer NP 0.50%E. methylchloroisothiazandnone (with) methylisothiazolinone 0.05%F. water is an amount of
Keratin 2.00% AFPP 5 * 10 of 100.00% shampoo Compositions VIII (" protein adjustment type shampoo ") A. water, 35.00% sodium laureth sulfate, 50.00% DL-panthenol, 2.00% coconut oleoyl amine DEA, 4.00% isostearoyl sodium lactate 3.00%B. Hydroxyproyl Trimethyl ammonium hydrolysis-6Uride 0.20%C. water is an amount of in-1.0% spice 0.20% DMDM
100.00 shampoo Compositions IX (" bead-blast (Pearlescent Treatment) shampoo ")
Decyl glucoside 5.00%
The aleuronat 4.00% of hydroxypropyl lauryl dimethyl ammonium hydrolysis
Myristyl ether sodium sulfate 27.00%
Glycol distearate (with) lauryl ether-4
(with) cocamidopropyl betaine
(Euperian?PK?300-AM)??????????????????????????3.00％
Propylene glycol (with) water (with) Herba Lamii albi (Lamium album)
Extract (with) foreign Caulis Hederae Sinensis (Hedera helix) extract
(with) strobile (Pinus (Pinus)) extract (with)
Chamomile (Anthemis nobilis) extract
(with) Nasturtium officinale (Nasturtium officinale)
Extract (with) Amica montana extract (with)
Fructus Arctii (Arctium lappa) extract
(with) Herba Rosmarini Officinalis (Rosemarinus officinalis)
Extract (Prodhyatif Hair Treatment,
Pro’Hyg?Labs)?????????????????????????????????5.00％
AFPP??????????????????????????????????????????5×10 -6-1.0％
Sodium chloride 2.10%
Water and preservative agent are an amount of
100.00% shampoo Compositions X (" shampoo that is used for dry scalp and dandruff ") an amount of B. Magnesiumaluminumsilicate of A. water 1.00%C. Herba bromi japonici (Avena sativa) albumen (Microat E, Tri-K) (Kelate 220 for 1.00%D.EDTA four sodium, Tri-K) 0.20% methyl parahydroxybenzoate (Trisept M, Tri-K) 0.30%E. hydroxypropyl emthylcellulose
(Methocel J1 2MS, Dow Chem) 1.00%F. cocamidopropyl betaine 5.00%
Glycerol 2.00%
Sodium N-lauroyl sarcosinate 20.00%
Lauramide DEA 2.00%
Sodium laureth sulfate 20.00%G. phosphoric acid is regulated an amount of J. panthenol of pH to 6.0-6.5 (DL-panthenol, Tri-K) 0.50%
Imidazolidinyl urea (Tristat IU, Tri-K) 0.50%
AFPP?????????????????????????????????????????5×10 -6-1.0％
The function lauryl sulfate ester triethanolamine 10.00 foaming/cleaning agent lauroyl sodium sulfate 2.80 the same AFPP 5 * 10 of the horizontal % composition of 100.00% shampoo Compositions XI composition -6Function lauryl sulfate ester triethanolamine 8.00 foaming/cleaning agent coconut monoethanol amides 4.00 foam improvers of-1.0 anti-fungus polypeptide hydroxypropyl emthylcelluloses 1.00 thickening agent water/preservative agent/spice/wait to add to the pH that 100 usefulness NaOH/ citric acids are regulated said composition. shampoo Compositions XII (adjustment type antidandruff shampoo) the horizontal % compositions of composition/foam stabiliser ethylene glycol monostearate 4.00 opaque/pearling agent NaCl 0.50 thickener polyethylene glycol 0.50 adjusting viscosity AFPP 5 * 10-6-1.0 anti-fungus polypeptide water/spices/wait to add to function sodium laureth sulfate 9.25 foaming/cleaning agent sodium N-lauroyl sarcosinates 2.45 the same cocamidopropyl propyl amide amine oxide 0.60 mildness additive/foams that 100 usefulness citric acids are regulated pH value shampoo Compositions XIII (adjustment type antidandruff shampoo) the horizontal % composition of composition of said composition
Stabilizing agent PEG-7 glyceryl cocoate 2.00 emollient/mildness adds
Agent Crotein Q (quaternary ammoniated collagen) 0.25 regulates composition AFPP 5 * 10 -6The function sodium laureth sulfate 10.50 foaming/cleaning agent coconut oil diethanol amides 2.50 foam stabilisers/shampoo that adds to the horizontal % composition of 100 shampoo Compositions XIV compositions such as-1.0 anti-fungus polypeptide water/spice/wait
Thickening agent AFPP 5 * 10 -6-1.0 anti-fungus polypeptide water/spice/wait to add to the pH to 6.0-6.5 that 100 usefulness citric acid/NaOH regulates said composition.The function lauryl sulfate ester triethanolamine 14.00 foaming/cleaning agent Briphos O3D of the horizontal % composition of shampoo Compositions XV composition *1.50 regulate composition AFPP 5 * 10 -6-1.0 anti-fungus polypeptide Empicol WP40** 10.00 opaque/pearling agent water/spice/wait to add to 100 *Oil base-3EO phosphate ester (Oleyl-3EO phosphate) *The proprietary mixture of sodium laureth sulfate, ethylene glycol monostearate and glycol distearate is provided by Albright and Wilson.The function sodium laureth sulfate 7.00 foaming/cleaning agent lauryl sulfate ester triethanolamine 5.64 the same Tegobetane L7 of the horizontal % composition of shampoo group thing XVI composition *4.80 foam stabiliser PEG-2 stearate 3.00 viscosity modifier AFPP 5 * 10 -6-1.0 anti-fungus polypeptide water/spice/wait to add to 100 *The function sodium laureth sulfate 9.80 foaming/cleaning agent cocamidopropyl betaine 4.80 foam stabilisers/mildness of the horizontal % composition of cocamidopropyl betaine shampoo Compositions XVII composition
Additive A ntil 141 liquid 0.50 viscosity modifier AFPP 5 * 10 -6-1.0 anti-fungus polypeptide water/spice/wait to add to 100 *The proprietary mixture of the propylene glycol that Yh.Goldschmidt AG provides/PEG-55 propylene glycol oleate.
The following discloses the example of other antidandruff shampoo Compositions, in anti-fungus polypeptide wherein of the present invention can be included in, and optionally with the antidandruff substitution of materials that exists in the said composition:
WO 99/13830 discloses the shampoo Compositions that contains following composition: a) triazole of effective dose, b) detersive surfactant, and c) carrier;
WO 99/39683 discloses the shampoo Compositions that contains following composition: a) about 7%-about 30% weight is selected from anion surfactant, the detersive surfactant of amphoteric surfactant and its mixture, b) antimicrobial of about 10% weight of about 0.1%-, c) suspending agent of about 0.5%-about 10% weight, d) the cationic guar gum polymer with about 0.1-about 3meg/mg charge density of about 0.01%-about 1.0% weight, e) be selected from Borneolum Syntheticum, Camphora, eucalyptole, methane, glycosyl-single  base-acetas (glycosyl-monomenthyl-acetate), menthol, 3-1- Ethylene Oxide, Mentha piperita, Herba Menthae Rotundifoliae, with their freshener (cool-feeling agent) of mixture, and f) water of about 40%-about 92% weight, wherein, cationic guar gum polymer at least about 50% weight is the agglomerate form, and described agglomerate contains detersive surfactant and cationic guar gum polymer;
WO 97/39096 discloses and has contained the Antimicrobe compound that is selected from some 1-hydroxyl-6-substituted pyridines-2-ketone and 2-thione compounds and the shampoo Compositions of shampoo surfactant, and wherein, the pH regulator of this hair-treatment composition is at least 7;
WO 97/26854 discloses the shampoo Compositions that contains following composition: a) about 7%-about 30% weight is selected from anion surfactant, amphoteric surfactant, zwitterionic surfactant, with their detersive surfactant of combination, b) antimicrobial of about 0.1%-about 10% weight, c) suspending agent of about 0.5%-about 10% weight, d) the cationic guar gum polymer with about 0.01meq/mg-about 3meq/mg charge density of about 0.01%-about 1.0% weight, and e) water of about 40%-about 92% weight, wherein, the cationic guar gum polymer of at least 50% weight is the agglomerate form, and the described cohesion bodily form contains detersive surfactant and cationic guar gum polymer;
WO 97/47275 discloses and has contained antidandruff agent, particularly rinse products such as shampoo, medicinal shampoo or the hair rinse liquid (rinse) of clotrimazol as activating agent;
WO 95/02389 discloses the antidandruff shampoo Compositions that contains following composition: a) about 5%-about 29.5% weight is selected from alkyl sulfate and alkyl ethoxylate sulfate, its acid, with their anion surfactant of mixture, b) the N-acylamino acid anion surfactant of about 0.5%-about 5% weight and its salt, c) the graininess antidandruff agent of about 0.1%-about 10% weight, d) crystalline suspending agent that is used for described antidandruff active component of about 0.5%-about 10% weight, e) water of about 40%-about 89% weight, wherein the concentration of total detersive surfactant is about 10%-about 30% in described compositions, composition b): composition weight ratio a) is at least about 1: 20, and described compositions does not have beet alkali surface activator and alkanolamide foam booster substantially;
WO 95/17880 discloses the shampoo Compositions that contains following composition: a) surfactant system that contains following material of about 5%-about 40% weight: (i) this surfactant system of 80%-about 99% weight is an anion surfactant, they are the alkyl ethoxylate sulfate and the alkyl sulfate of ratio from about 1: 1 to 1: 0, this surfactant system of (ii) about 1%-20% weight is a polyhydroxy fatty acid amide surfactant, b) water of the about 35%-about 95% weight functional mass of about 0.05%-about 25% weight, and c); With
WO 92/14440 discloses the lamella pyridine sulfur zinc activating agent that contains surfactant, specific granular size, the synergist of suspending agent, water and this activating agent.
The following discloses the example that wherein can comprise other shampoo Compositions of anti-fungus polypeptide of the present invention:
WO 98/00498 discloses a kind of compositions that contains surfactant system, this surfactant system comprises dianion or alkoxylate dianionic surfactant and one or more other cosurfactants, this dianion or alkoxylate dianionic surfactant have the anion substituent that has connected two at least 3 atoms of being separated by, the structural framework that contains at least 5 carbon atoms, wherein, an anion substituent is the sulfate group that sulfate group or alkoxyl connect, and another anion substituent is selected from sulfate and the sulfonate that optionally has been connected alkoxyl.
WO 97/14405 discloses following shampoo Compositions, said composition contains the suspending agent of the siloxanes hair conditioner of the detersive surfactant of 5%-about 50% weight of having an appointment, about 0.05-about 10% weight, about 0.1%-about 10% weight, the selected poly alkylene glycol of about 0.025%-about 1.5% weight (preferably has about 1,500-about 2, and optional one or more other materials that can in shampoo or adjustment type compositions, use the Polyethylene Glycol of 500 ethoxylation degrees) and water;
WO 97/25965 discloses following shampoo Compositions, this shampoo Compositions of wherein per 100 parts of weight contains the 5-about 50 parts of sensitive surfactant mixture that contain following composition of having an appointment: a) account at least a powerful anionic surfactant of about 10-about 60% weight of this mixture, b) account at least a amphoteric surfactant and the c of about 10-about 40% weight) account at least a alkyl saccharide non-ionic surface active agent of about 10-about 60% weight of this mixture;
WO 97/14406 discloses following shampoo Compositions, this shampoo Compositions is except that anionic amino acid derivative surfactant, also contain the decontamination anion surfactant, be selected from anionic amino acid derivative surfactant, amphoteric surfactant, the surface of stability activating agent of cationic surfactant and their mixture, be selected from aliphatic alcohol, fatty acid, the aliphatic alcohol derivant, the aliphatic compound of derivative of fatty acid and their mixture, be selected from the hair conditioner of nonvolatile dispersed polyorganosiloxane regulator and their mixture, and water;
WO 98/04233 discloses the shampoo Compositions that contains alkoxylate polyalkylene amine and one or more detersive surfactants, in further embodiment, disclose following hair conditioning shampoo Compositions, this hair conditioning shampoo Compositions contains about 0.01%-about 10% alkoxylate polyalkylene amine, about cationic surfactant regulator of 0.01%-about 20%, about detersive surfactant of 5%-about 50% and the about water of calculating by weight of 25%-about 90%;
WO 98/04238 discloses and has contained the shampoo Compositions of changing poly-alkoxylation polyalkylene amine and detersive surfactant season (ammonium), in further embodiment, disclose contain calculate by weight about 0.01%-about 10% change poly-alkoxylation polyalkylene amine, about cationic surfactant regulator of 0.01%-about 20%, about 5% detersive surfactant and the adjustment type shampoo Compositions of about water of 20%-about 90% season (ammonium);
WO 98/04239 discloses the shampoo Compositions that contains following composition: a) carbon chain lengths of about 0.1%-about 10% weight is 10 or the short-chain alkyl sulfate surfactant of carbon atom still less, b) the pure and mild c of ethoxylation of about 0.1%-about 10% weight) about 1%-about 60% weight be selected from anion surfactant except that short-chain alkyl sulfate a), except that b) ethoxylated alcohol non-ionic surface active agent, both sexes and cationic surfactant and the cosurfactant of their mixture, d) water;
WO 98/18433 discloses following shampoo Compositions, this shampoo Compositions contains the anion surfactant that is selected from of 5%-about 50% weight of having an appointment, having at the pH place of said composition is the amphion or the amphoteric surfactant of anionic linking group, with their surfactant of compositions, the cationic charge density with about 0.2meq/mg-about 7meq/mg of about 0.025%-about 3% weight and about 5, the organic cationic polymer of 000-about 1,000 ten thousand molecular weight, the water-insoluble hair amorphous polymer of about 0.1%-about 10% weight, the water-insoluble solvent flashing of about 0.1%-about 10% weight, with about 0.05%-about 5% weight as the selected cationic substance of the spreading agent of above-mentioned hair amorphous polymer and the water of about 22%-about 94.3% weight;
WO 98/04241 discloses the shampoo Compositions that contains following material: a) about 1%-about 60% proportion is selected from anion surfactant, nonionic, both sexes and cationic surfactant, with their surfactant of mixture, b) the liquid polyol carboxylate that contains at least 4 acid esters groups of about 0.001%-about 10% weight, wherein polyol moiety is selected from sugar or the sugar alcohol that contains 4-about 12 oh groups of having an appointment, each carboxylic moiety has about 8-about 22 carbon-based groups, and this liquid polyol carboxylate has and is lower than about 30 ℃ complete fusing point, and c) about 0.001%-about 4% weight has a general molecular formula :-H (OCH 2CH 2) nThe nonionic polyethylene polymer of OH, wherein n is the ethoxylation meansigma methods in about 1,000-about 25,000 scopes, and d) water;
WO 98/18435 discloses following shampoo Compositions, and this shampoo Compositions comprises surfactant component in containing the shampoo of granular size scope less than the insoluble dispersion nonionic of the graininess of about 0.15 μ m regulator, crystal reagent (crystalline agent) and deposited polymer;
WO 98/50007 discloses the shampoo Compositions that contains following composition: a) combination that is selected from anion surfactant and amphoteric surfactant of about 5%-about 50% weight, and the surfactant composition of the combination of anion surfactant and zwitterionic surfactant, b) cationic cellulose polymer that is selected from about 0.2meq/g-about 2meq/g cationic charge density of about 0.025%-about 3% weight, cation melon ear wood glue derivant, cationic deposition polymer with its mixture, c) about 0.5%-about 10% weight have about 2meq/g above-the organic cation hair amorphous polymer of cationic charge density below about 4.75meq/g, and d) water of about 27%-about 94.5% weight.It is special that effectively those contain the Polyquaternium-16 as the cationic hair amorphous polymer, as the Polyquaternium-10 of cationic deposition polymer, and the hair setting shampoo Compositions that comprises the surfactant substrate of Zetesol AP and cocamidopropyl betaine;
WO 99/38475 discloses following shampoo Compositions, this shampoo Compositions contains the anion surfactant that is selected from of 5%-about 50% weight of having an appointment, having at the pH place of said composition is the amphion or the amphoteric surfactant of anionic linking group, surfactant with their combinations, about 0.025%-about 3% weight have about 0.2meq/mg-about 7meq/mg cationic charge density and about 5, the organic cationic polymer of 000-about 1,000 ten thousand molecular weight, the water-insoluble solvent flashing of about 0.1%-about 10% weight, with the crystal hydroxyl stabilizing agent of about 0.005%-about 2.0% weight and the water of about 26.5%-about 94.9% weight;
WO 99/38476 discloses following shampoo Compositions, this shampoo Compositions contains the surfactant that is selected from anion surfactant, amphion or amphoteric surfactant and their combination of 5%-about 50% weight of having an appointment, organic or the polysiloxane grafted hair amorphous polymer of about 0.1%-about 1.0% weight, water with about 40%-about 94.9% weight, wherein send out sense index (Hair Feel Index, HFI) be at least about 0.65, (CurlRetention Value is at least about 70 CRV) to the hair style persistence value;
WO 97/35546 discloses following shampoo Compositions, this shampoo Compositions contains anionic detersive surface activity composition, anion, the cationic hair telomerized polymer, viscosity with about 1-about 300 centipoises of having of about 0.01%-about 1.0% weight, and meet molecular formula (I) and each the synthetic ester of water-insoluble (II), and viscosity with about 1-about 399 centipoises, be selected from hydrocarbon ils, organic water-insoluble of the aliphatic ester except that above-mentioned synthetic ester and its combination is regulated oil, wherein molecular formula (I) and (II) in R1 be alkyl with 7-9 carbon atoms, alkenyl, hydroxyalkyl or hydroxyl alkenyl, n is that value is 2-4 positive integer, R2 is the alkyl with 8-10 carbon atoms, alkenyl, hydroxyalkyl or hydroxyl alkenyl, Y are the alkyl with about 2-about 20 carbon atoms, alkenyl, the alkyl of hydroxyl or carboxyl substituted or alkenyl.Described organic adjusting oil preferred polyolefm.
[R1-CO-O] n-Y????(I)????[R2-O-CO] n-Y????(II)；
WO 99/24004 discloses the shampoo Compositions that contains the following composition of calculating by weight: a) about polyhydrophilic anion surfactant of 0.05%-about 50%, b) about cationic conditioning agent that is selected from cationic surfactant, cationic polymer and its combination of 0.05%-about 20%, c) water carrier about silicone compounds of 0.01%-about 20%, and d);
WO 98/50011 discloses the shampoo Compositions that contains following composition: a) surface active ingredient that has an anionicsite at the pH place of said composition of about 5%-about 50% weight, b) the cationic deposition polymer of about 0.025%-about 3% weight, c) the hair amorphous polymer of the generation foul smell of about 0.1%-about 10% weight, d) abnormal smells from the patient of about 0.0075%-about 2.5% weight is covered perfume base (odor masking base), and e) water of about 25%-about 94.5% weight.This abnormal smells from the patient cover perfume base contain having of (calculating) about 15%-about 75% weight by the weight of this perfume base about more than 250 ℃ boiling point ionone spice, about 5%-about 65% weight have the about Moschus of boiling point and the high volatile volatile spice with about boiling point below 250 ℃ of about 20%-about 80% weight more than 250 ℃.Also disclose further to contain and produced the liquid-carrier of smelling gas is smelt the polymer of gas with generation in dissolving or the dispersion said composition shampoo Compositions;
WO 99/13828 discloses the shampoo Compositions that contains following composition: a) fluorescent whitening agent of effective dose, b) anionic detersive surfactant, c) amphoteric detersive surfactants, d) non-ionic detersive surfactant, and e) carrier, wherein the pH of said composition is not higher than about 7;
WO 99/13829 discloses the shampoo Compositions that contains following composition: a) fluorescent whitening agent of effective dose, b) detersive surfactant, the c) polyvalent cation of effective dose, and d) carrier;
WO 93/18737 discloses following shampoo Compositions, and this shampoo Compositions contains the imidazoline salt type amphoteric surfactant of alkyl ethoxylate sulfate surfactant, particular type, preferably dissolves and the crystal suspending agent of recrystallization and the water of relatively small amount in premixed compositions.Preferred compositions contains the suspending agent and the water of alkyl ethoxylate sulfate surfactant, imidazoline type amphoteric surfactant, beet alkali surface activator, recrystallization; With
WO 97/35549 discloses following shampoo Compositions, this shampoo Compositions contains specific surface active agent composition in the shampoo that comprises insoluble dispersion regulator, the organic adjusting oil of low viscosity and selected soluble cellulose cationic organic polymer hair conditioner, this specific surfactant component comprises ethoxylated alkyl sulfates surfactant and the amphoteric surfactant with about 1-about 8 mole oxygen ethylene unit.
Embodiment material and method
By the WO 94/01459 described generation of anti-fungus polypeptide shown in Figure 1 (AFPP) and the purification subsequently of carrying out.In brief, this anti-fungus polypeptide is prepared as follows: huge aspergillosis strain is
This experiment uses the fungus strain preservation center (CBS) that is preserved in, preserving number as the huge aspergillosis strain of CBS 526.65 to be.The cultivation that the huge aspergillosis strain that produces AFPP is
The agar culture medium that use is prepared to 1000ml by 39g potato dextrose agar (Difco product) adding distil water carries out agar slant and cultivates.With above-mentioned huge aspergillosis strain is this agar slant of inoculation, and 26 ℃ of one weeks of growth.Deep layer is cultivated
With 5ml by above-mentioned obtain the preparation of huge aspergillosis agar slant culture contain 10 6The spore suspension inoculation of spore/ml contains the 500ml conical flask of 100ml AMC culture medium (15g meat extract, 20g peptone, 20g corn starch, 5g NaCl, 1ml Pluronic, 1 premium on currency).This conical flask was cultivated recyclable afterwards AFPP 3 days at 30 ℃ of velocity fluctuations with 220rpm.The separation of AFPP, purification and determined amino acid sequence
The above-mentioned institute fermentation culture that obtains is centrifugal, mycelium suspended in the Tris of pH7 buffer salt solution, carry out then the 2nd time centrifugal.Merge two times centrifugal supernatant, and with its aseptic filtration.Regulate between the pH to 6.5-9 of the supernatant goods that obtain, these supernatant goods are applied on the cation exchange resin of having crossed with the phosphate buffer balance of pH6.5 before application (SSepharose Fast Flow).By using high ionic strength buffers liquid, realize from this resin elution active component as containing the buffer of 20mM phosphate, 1.5mM NaCl, pH6.5.If necessary, be lower than with ionic strength or near the 10mM of pH6.0 the dilution of phosphatic buffer or to this buffer dialysis after, can repeat said procedure.If necessary, the eluting in this second step carries out with gradient elution.The purity of active component is estimated by HPLC.
Before the antifungal property of test to pityrosporum ovale, with the active component that merges with 0.22 μ m filter (Millipore) filtration sterilization.
The AFPP of purification carries out the S-carboxy methylation with 1990 described methods such as Nakaya, and uses the reversed-phase HPLC desalination.By producer's description operation, the carboxymethylated AFPP of this S-is carried out the n terminal amino acid sequencing on Applied Biosystem 473A sequenator.Extinction coefficient
The extinction coefficient of AFPP are estimated from aminoacid sequence shown in Figure 1 with following formula:
Figure A9981392700301
(Gill and von Hippel, 1989) are (No.Trp), (No.Tyr) and (No.Cys) be the number of Trp, Tyr and Cys residue in the described aminoacid sequence wherein.
The extinction coefficient that calculate the 280nm place according to this formula are 1.3.All polypeptide are measured all extinction coefficient and the OD based on this calculating 280Measured value.The preparation of anti-AFPP antibody
Will be by producing as mentioned above and the AFPP of purification is diluted to 25-250 μ g/ml concentration in phosphate buffer salt (pH6.5-8).Adopt basic immunization protocol, with the purified polypeptide immunize rabbit in the Freund's complete adjuvant according to 1989 described standardization programs such as Hudson.Collect serum, use the above-mentioned purification AFPP that obtains of institute, in single composition radiation immunity diffusion test or the test of Western trace, measure the multi-specificity antibody of anti-AFPP in this serum as antigen.These tests can be carried out according to 1989 described programs such as standardization program such as Hudson.This antibody can be by the standard method purification, and these methods such as use are fixed to the standard immunoassay adsorption technology of the purification AFPP on the carrier, for example 1989 described methods such as Hudson.The mensuration of the antibody response of AFPP variant of the present invention
AFPP variant and the above-mentioned reactivity that obtains antibody or contain the serum of antibody can be measured in substantially by the 1989 described single composition radiation immunities diffusions carried out such as Hudson or Western trace.
The inhibition of embodiment 1 yeast pityrosporum ovale
Pityrosporum ovale in the microtitration plate that contains the culture medium that American type culture collection recommends in 37 ℃ of growths.Every liter of this culture medium contains 30g Sha Shi glucose culture medium (Sabouraud ' s glucose broth), 5g yeast extract and 2ml olive oil.
By being dissolved in, AFPP prepares the standard solution that contains AFPP in the 10mM phosphate buffer (pH7.5).
As shown in Figure 2, each microtitration plate comprises 4 identical perpendicular roads, and each perpendicular road contains
-one hole that only contains culture medium (200ml) and 50ml 10mM phosphate (pH7.5) is (in contrast to test the aseptic of this culture medium.Comprise phosphate buffer and be for to compare experiment condition identical with the zymic hole of inoculation doleiform).
-one except that having inoculated hole with above-mentioned hole identical the pityrosporum ovale.
Inoculated pityrosporum ovale and contained 0.005 OD for-one 280The hole of the AFPP of concentration (about 5mg AFPP/ liter).
Inoculated pityrosporum ovale and contained 0.027 OD for-one 280The hole of the AFPP of concentration.
Inoculated pityrosporum ovale and contained 0.068 OD for-one 280The hole of the AFPP of concentration.
Inoculated pityrosporum ovale and contained 0.136 OD for-one 280The hole of the AFPP of concentration.
Tracking is as the pityrosporum ovale growth of time function.This yeast is growth equably not, but with big reunion growth.The existence of this fact and olive oil makes and can not measure growth with spectrophotography.Therefore, cell is suspended again, get 10 μ l and be layered on the agar that contains same medium.On microtitration plate and the solid medium flat board roughly the mensuration of growth provided identical result (seeing Table 1).Result displayed is the average growth in 4 perpendicular roads in the table 1.
The size of the bacterium colony that is used to inoculate is depended in this growth.Bacterium colony is big more, and then the growth on flat board is fast more.In the present embodiment, culture medium has only been inoculated a petite.As shown in table 1 below, this has produced the trophophase of a prolongation.But, if culture medium inoculated a bigger bacterium colony, result shown in the table 1 is also identical, just trophophase has shortened.Table 1
Concentration (the OD of AFPP 280) The 3rd day The 6th day The 7th day The 8th day The 10th day The 13rd day
Culture medium is only arranged ????0 ????0 ????0 ????0 ????0 ????0
0 ????0 ????× ????×× ???×× ???××× ???×××
0.005 ????0 ????0 ????× ????× ????×× ???×××
0.027 ????0 ????0 ????0 ????× ????× ????××
0.068 ????0 ????0 ????0 ????× ????× ????×
0.136 ????0 ????0 ????0 ????0 ????0 ?????×
0: in this hole, do not observe growth
*: observe a little growth at the center in this hole
* *: observed some growths at the center in this hole, and observes less life at the edge
Long
* * *: observe powerful grown junction opinion in whole media surface:
The present invention illustrates that clearly AFPP stops the growth of yeast pityrosporum ovale.Even also suppressing this fact of growth of pityrosporum ovale, the AFPP of extremely low concentration (for example about 5mg/ liter) makes that AFPP is suitable for using in treatment or prevention dandruff.
List of references Gill that quotes in the description and yon Hippel, Anal.Biochem.182,319-26,1989; Hudson, L., and Hay, F., practical immunology (Practical Immundogy), the 3rd edition (1989), Blackwell Scientific Publications; Lipman and Pearson, science (Science) 227,1435 (1985); Nakaya, K. etc., Eur.J.Biochem.193,31-38,1990, " from the aminoacid sequence and the disulphide bridges of the isolating anti-fungus polypeptide of huge aspergillosis "; Wnendt, S etc., nucleic acids research (Nucleic Acids Research), the 18th volume, the 13rd phase: 3987,1990, " clone of the cDNA of the huge aspergillar antifungal protein of encoding and nucleotide sequence, and the preliminary feature analysis of this natural gene ".

Claims (18)

1. be applicable to the anti-dandruff composition that is applied on human hair or the scalp, it comprises the anti-fungus polypeptide that contains aminoacid sequence shown in Figure 1 or its variant of effective dose, and described variant is
I) can with the polypeptide of following antibody response, described antibody can with at least one epi-position reaction of polypeptide with aminoacid sequence shown in Figure 1, or
II) the homologous substantially polypeptide of its aminoacid sequence and amino acid sequence of polypeptide shown in Figure 1.
2. according to the compositions of claim 1, wherein anti-fungus polypeptide is from microorganism.
3. according to the compositions of claim 2, wherein anti-fungus polypeptide is from fungus, particularly the fungus of aspergillus.
4. according to the compositions of claim 3, wherein anti-fungus polypeptide is from the fungus that belongs to huge aspergillosis, A. pallidus, excellent aspergillosis, A. longivesica, A. rhizopodus or A.clavatonanicus.
5. according to the compositions of claim 4, wherein anti-fungus polypeptide is from belonging to huge aspergillar fungus.
6. according to the compositions of claim 5, wherein anti-fungus polypeptide is from huge aspergillar CBS 526.65 strains.
7. according to each compositions of aforementioned claim, wherein anti-fungus polypeptide contains aminoacid sequence shown in Figure 1.
8. according to the compositions of claim 7, wherein anti-fungus polypeptide is made up of aminoacid sequence shown in Figure 1.
9. according to each compositions of claim 1-6, one or more amino acid residue on the 4th, 24,32,42 and 50 of the anti-fungus polypeptides wherein shown in Figure 1 is substituted by the naturally occurring amino acid residue of another kind.
10. according to the compositions of claim 9, wherein anti-fungus polypeptide contains aminoacid sequence shown in Figure 1, wherein the 4th Pro is substituted by Asn or Asp, the 24th Gly is substituted by Ala, the 32nd Arg is substituted by Lys or Val, the 42nd Leu is substituted by Phe, and/or the 50th His is substituted by Tyr.
11. compositions according to claim 10, wherein anti-fungus polypeptide is made up of aminoacid sequence shown in Figure 1, wherein the 4th Pro is substituted by Asn or Asp, the 24th Gly is substituted by Ala, the 32nd Arg is substituted by Lys or Val, the 42nd Leu is substituted by Phe, and/or the 50th His is substituted by Tyr.
12. according to each compositions of aforementioned claim, its adopts the form of shampoo, solution, suspension, emulsion, gel, foam or paste.
13. according to the compositions of claim 12, it adopts the form of shampoo.
14. according to each compositions of aforementioned claim, wherein said active component is in based on said composition weight about 5 * 10 -6The amount of %-about 10% exists.
15. the defined anti-fungus polypeptide of each of claim 1-11 is in the treatment of dandruff or the application in the prevention.
16. the method for treatment or prevention dandruff, described method comprise each the defined compositions contact hair with 1-11 each defined anti-fungus polypeptide of effective dose or claim 12-14.
17. the defined anti-fungus polypeptide of each of claim 1-11 is used for the treatment of or prevents application in the compositions of dandruff in preparation.
18. according to the application of claim 17, wherein said compositions is each defined compositions of claim 12-14.
CN99813927A 1998-11-30 1999-11-26 Anti-dandruff composition comprising antifungal polypeptide Pending CN1329500A (en)

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DE60226724D1 (en) * 2001-05-04 2008-07-03 Novozymes As ANTIMICROBIAL POLYPEPTIDE
ATE395902T1 (en) * 2003-10-10 2008-06-15 Frenchtop Natural Care Product SHAMPOO AND BODY CLEANSER
JP4745914B2 (en) * 2005-12-01 2011-08-10 花王株式会社 Hair cleanser
KR101425331B1 (en) 2007-12-21 2014-08-01 바스프 에스이 Anti-dandruff compositions containing peptides
FR2954137B1 (en) * 2009-12-17 2012-04-20 Oreal USE OF PEPTIDES AS ANTIPELLICULAR AGENTS
EA201491525A1 (en) 2012-02-14 2014-12-30 Юниверсити Оф Джорджиа Рисерч Фаундэйшн, Инк. SPIRO [2.4] HEPTANS FOR THE TREATMENT OF INFECTIONS CAUSED BY FLAVIVIRIDAE
FR2998785B1 (en) * 2012-12-05 2014-11-28 Fauvert COMPOSITION FOR CLEANING AND CARING FOR HAIR AND / OR SCALP.
KR20220025914A (en) 2015-03-06 2022-03-03 아테아 파마슈티컬즈, 인크. β-D-2'-DEOXY-2'-α-FLUORO-2'-β-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT
WO2018013937A1 (en) 2016-07-14 2018-01-18 Atea Pharmaceuticals, Inc. Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection
CN116036114A (en) 2016-09-07 2023-05-02 阿堤亚制药公司 2' -substituted-N for RNA viral therapy 6 -substituted purine nucleotides

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