EP2200651A2 - Utilisation de polypeptides de type hydrophobine comme renforçateurs de pénétration - Google Patents

Utilisation de polypeptides de type hydrophobine comme renforçateurs de pénétration

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Publication number
EP2200651A2
EP2200651A2 EP08803103A EP08803103A EP2200651A2 EP 2200651 A2 EP2200651 A2 EP 2200651A2 EP 08803103 A EP08803103 A EP 08803103A EP 08803103 A EP08803103 A EP 08803103A EP 2200651 A2 EP2200651 A2 EP 2200651A2
Authority
EP
European Patent Office
Prior art keywords
acid
hydrophobin
esters
use according
penetration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08803103A
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German (de)
English (en)
Inventor
Thomas Subkowski
Marvin Karos
Heiko Barg
Claus Bollschweiler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Priority to EP08803103A priority Critical patent/EP2200651A2/fr
Priority to EP13174958.2A priority patent/EP2676680A1/fr
Publication of EP2200651A2 publication Critical patent/EP2200651A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • hydrophobin-polipeptides as penetration enhancers
  • the present invention relates to the use of hydrophobin polypeptides as penetration enhancers.
  • Penetration enhancers have gained increasing importance in recent years in various fields such as a component of cosmetic or pharmaceutical composition, pesticides or coating agents.
  • Transdermal penetration enhancers are known from WO 93/002669. It describes a combination of polar and nonpolar penetration enhancers in a drug-containing adhesive matrix in transdermal therapeutic systems.
  • polar penetration enhancers are polyhydric alcohols, as non-polar
  • Penetration enhancers called fatty acid esters.
  • the penetration enhancers cause an increase in the penetration rate of the drug, which are poorly soluble or insoluble in water steroid hormones.
  • the barrier function of the drug which are poorly soluble or insoluble in water steroid hormones.
  • penetration enhancer such as the above or dimethyl sulfoxide (DMSO)
  • Further penetration enhancers used in therapeutic preparations are, for example, mono- or polyhydric alcohols, such as ethanol, 1,2-propanediol or benzyl alcohol, saturated and unsaturated fatty alcohols having 8 to 10 carbon atoms, such as lauryl alcohol or cetyl alcohol, hydrocarbons, such as mineral oil, alkanes, Esters, azone such as i-Dodecylazacycloheptan ⁇ -one, propylene glycol, chitosan, saturated and unsaturated fatty acids such as stearic acid or oleic acid, fatty acid esters having up to 24 carbon atoms or dicarboxylic acid having up to 24 carbon atoms such as the methyl esters, ethyl esters, isopropyl esters, butyl esters, sec - butyl ester, isobutyl ester, tert.
  • mono- or polyhydric alcohols such as ethanol, 1,2-propanediol
  • penetration enhancers are SDS (sodium dodecylsulfate), dimethylformamide and N-methylformamide. In the field of crop protection, penetration enhancers are also used to ensure easier intake of pesticides.
  • Hydrophobins are small proteins of about 100 to 150 amino acids found in filamentous fungi, such as Schizophyllum commune. They usually have 8 cysteine units. Hydrophobins can be isolated from natural sources, but can also be obtained by genetic engineering, as disclosed, for example, by WO 2006/082251 or WO 2006/131564.
  • Hydrophobins are in a water-insoluble form on the surface of various fungal structures, e.g. Aerial hyphae, spores, fruiting bodies, distributed.
  • the genes for hydrophobins could be isolated from ascomycetes, deuteromycetes and basidiomycetes.
  • Some fungi contain more than one hydrophobing, e.g. Schizophyllum commune, Coprinus cinereus, Aspergillus nidulans.
  • different hydrophobins are involved in different stages of fungal development. The hydrophobins are believed to be responsible for different functions (van Wetter et al., 2000, Mol. Microbiol., 36, 201-210, Kershaw et al., 1998, Fungal Genet., Biol, 1998, 23, 18-33).
  • hydrophobins As a biological function for hydrophobins, in addition to reducing the surface tension of water to generate aerial hyphae, hydrophobization of spores is also described (Wösten et al., 1999, Curr. Biol., 19, 1985-88; Bell et al., 1992, Genes Dev. , 6, 2382-2394). Hydrophobins also serve to line gas channels in lichen fructoids and as components in the plant surface recognition system by fungal pathogens (Lugones et al., 1999, Mycol Res., 103, 635-640, Hamer & Talbot 1998, Curr. Opinion Microbiol. , Vol. 1, 693-697). The use of hydrophobins for various applications has been proposed in the prior art.
  • WO 96/41882 proposes the use of hydrophobins as emulsifiers, thickeners, surface-active substances, for hydrophilicizing hydrophobic surfaces, for improving the water resistance of hydrophilic substrates, for producing oil-in-water emulsions or for water-in-oil emulsions. Furthermore, pharmaceutical applications such as the production of ointments or creams and cosmetic applications such as skin protection or the production of hair shampoos or hair rinses are proposed.
  • EP 1 252 516 discloses the coating of various substrates, such as window, lens, biosensor, medical device, container, frame or
  • hydrophobins as penetration enhancers is not yet known.
  • the object of the invention was to provide a new use for hydrophobin.
  • the task should be solved, the active substances penetrating
  • a further object of the present invention is to provide cosmetic and / or pharmaceutical compositions containing hydrophobin as penetration enhancers which ensure improved uptake of the active ingredients, in particular without causing irritation of the skin or mucous membranes.
  • a further object of the present invention was to provide pesticides comprising hydrophobin as penetration enhancers which ensure improved uptake of the active ingredients, in particular without causing damage to the treated plants or environmental damage.
  • hydrophobin as a penetration enhancer
  • penetration enhancer and “penetration enhancer” are synonymous.
  • Penetration in the context of the present invention is the penetration of substances through a phase boundary.
  • a phase boundary in the sense of the present invention is the transition from one phase to the neighboring phase.
  • a phase in the sense of the present invention is an area within which no sudden change of any physical quantity occurs.
  • at least one physical or chemical property selected from the group consisting of density, electrical properties, magnetic properties, refractive index, chemical composition, crystal structure.
  • enhancement of penetration through a phase boundary means that in comparison to a control possessing identical chemical, biological, and physical properties, and under identical chemical biological and physical conditions or conditions, in the same time a larger one Amount of drugs penetrates the phase boundary or the same amount of active ingredients in a shorter time penetrates the phase boundary.
  • amplification of the penetration or the increased penetration, or an increased penetration of active substances through a phase boundary means that it is possible or improved to penetrate phase boundaries for active substances for which this phase boundary hitherto was impermeable or poorly permeable. This is in comparison to a control which has the identical chemical, biological, and physical properties, and under identical chemical biological and physical conditions or conditions, wherein in the same time a larger amount of active ingredients permeates the phase boundary or the same amount of active ingredients in a shorter time the phase boundary permeates.
  • Penetration enhancers are substances that increase the penetration of another substance through a phase boundary.
  • hydrophobin or “hydrophobins” is intended below to mean polypeptides of the general structural formula (I)
  • X n -C 1 -Xi -5 ⁇ -C 2 -X ⁇ -5 "c3 - ⁇ 1 -100- c4 - ⁇ 1 -100 " c5 - ⁇ 1 -50- c6 - ⁇ 0-5 ⁇ c7 - ⁇ 1 - 50 ⁇ c8 - Xm (I), where X is selected for each of the 20 naturally occurring amino acids (Phe, Leu, Ser, Tyr, Cys, Trp, Pro, His, GIn, Arg, Ne Met, Thr, Asn, Lys, VaI, AIa, Asp, GIu, GIy).
  • the radicals X may be the same or different.
  • the indices standing at X each represent the number of amino acids in the C represents cysteine, alanine, serine, glycine, methionine or threonine, wherein at least four of the radicals named C are cysteine, and the indices n and m independently of one another represent natural numbers between 0 and 500, preferably between 15 and 300.
  • the polypetides according to formula (I) are further characterized by the property that at room temperature after coating a glass surface, they increase the contact angle of a water droplet of at least 8 °, 10 °, 20 °, preferably at least 25 ° and particularly preferably 30 °, in each case compared with the contact angle of a water droplet of the same size with the uncoated glass surface.
  • the amino acids designated C 1 to C 2 are preferably cysteines; but they can also be replaced by other amino acids of similar space filling, preferably by alanine, serine, threonine, methionine or glycine. However, at least four, preferably at least 5, more preferably at least 6, and in particular at least 7, of the positions C 1 to C 1 should consist of cysteines. Cysteines can either be reduced in the proteins according to the invention or form disulfide bridges with one another. Particularly preferred is the intramolecular formation of C-C bridges, in particular those with at least one, preferably 2, more preferably 3 and most preferably 4 intramolecular disulfide bridges. In the exchange of cysteines described above by amino acids of similar space filling, it is advantageous to exchange in pairs those C positions which are capable of forming intramolecular disulfide bridges with one another.
  • cysteines, serines, alanines, glycines, methionines or threonines are also used in the positions indicated by X, the numbering of the individual C positions in the general formulas may change accordingly.
  • radicals X n and X m may be peptide sequences that are naturally also linked to a hydrophobin. However, one or both of the residues may be peptide sequences that are not naturally linked to a hydrophobin. Including such radicals X N and / or X m are to be understood, in which a naturally occurring in a hydrophobin peptide sequence is extended by a non-naturally occurring in a hydrophobin peptide sequence.
  • X n and / or X m are naturally non-hydrophobin-linked peptide sequences, such sequences are generally at least 20, preferably at least 35 amino acids long. They may, for example, be sequences from 20 to 500, preferably 30 to 400 and particularly preferably 35 to 100 amino acids.
  • Such a residue, which is not naturally linked to a hydrophobin, will also be referred to below as a fusion partner.
  • the proteins consist of at least one hydrophobin part and one
  • Fusion-hydrophobins from fusion partner and hydrophobin part are described for example in WO 2006/082251 (page 2, line 18 to page 5, line 25), WO 2006/082253 (page 2, line 20 to page 6, line 13) and WO 2006/131564 (Page 2, line 17 to page 6, line 26).
  • the fusion partner portion can be selected from a variety of proteins. Only a single fusion partner can be linked to the hydrophobin moiety, or several fusion partners can also be linked to a hydrophobin moiety, for example at the amino terminus (X n ) and at the carboxy terminus (X m ) of the hydrophobin moiety. However, it is also possible, for example, to link two fusion partners with a position (X n or X m ) of the protein according to the invention.
  • fusion partners are proteins that occur naturally in microorganisms, in particular in E. coli or Bacillus subtilis.
  • fusion partners are the sequences yaad (SEQ ID NO: 16 in WO 2006/082251), yaae (SEQ ID NO: 18 in WO 2006/082251), ubiquitin and thioredoxin.
  • fragments or derivatives of said sequences which comprise only a part, for example 70 to 99%, preferably 5 to 50%, and particularly preferably 10 to 40% of said sequences, or in which individual amino acids or nucleotides are opposite the said sequence are changed, wherein the percentages in each case refers to the number of amino acids.
  • the fusion hydrophobin has in addition to the fusion partner mentioned as one of the groups X n or X m or as a terminal
  • affinity domain affinity tag / affinity tail
  • anchor groups which can interact with certain complementary groups and can serve the easier workup and purification of the proteins.
  • affinity domains include (His) -, (Arg) -, (Asp) -, (Phe) k - or
  • Affinity domain or a naturally or not naturally associated with a hydrophobin residue X n or X m is extended by a terminal affinity domain.
  • hydrophobins used according to the invention are hydrophobins according to the structural formulas (I), (II) and (III) as well as fusion hydrophobins.
  • hydrophobins used according to the invention may also be modified in their polypeptide sequence, for example by glycosylation, acetylation or else by chemical cross-linking, for example with glutaric dialdehyde.
  • Derivatives is the change of surface properties when the surfaces are coated with the proteins.
  • the change in the surface properties can be experimentally determined, for example, by measuring the contact angle of a water drop before and after coating the surface with the protein and determining the difference between the two measurements.
  • contact angle measurements is known in principle to the person skilled in the art.
  • the measurements refer to room temperature and water drops of 5 ⁇ l and the use of glass slides as substrate.
  • the exact experimental conditions for an exemplary method for measuring the contact angle are shown in the experimental part.
  • the fusion proteins used according to the invention have the property of increasing the contact angle by at least 20 °, preferably at least 25 °, particularly preferably at least 30 °; 40 °, 45 °, in particular 50 °, in each case compared with the contact angle of a water droplet of the same size with the uncoated glass surface.
  • hydrophobins for carrying out the present invention are the hydrophobins of the type dewA, rodA, hypA, hypB, sc3, basfi, basf2. These hydrophobins including their sequences are disclosed, for example, in WO 2006/82251. Unless otherwise indicated, the following refer to Sequences on sequences disclosed in WO 2006/82251. An overview table with the SEQ ID numbers can be found in WO 2006/82251 on page 20 (line 1 to line 5).
  • fusion proteins yaad-Xa-dewA-his SEQ ID NO: 20
  • yaad-Xa-rodA-his SEQ ID NO: 22
  • SEQ ID NO: 24 with the polypeptide sequences given in parentheses and the nucleic acid sequences coding therefor, in particular the sequences according to SEQ ID NO: 19, 21, 23. Particular preference may be given to yaad-Xa-dewA-his (SEQ ID NO: 20) be used. Also, proteins which, starting from the amino acid sequences shown in SEQ ID NO. 20, 22 or 24 polypeptide sequences represented by exchange, insertion or
  • Deletion of at least one, up to 10, preferably 5, more preferably 5% of all amino acids result, and still have at least 50% of the biological property of the starting proteins, are particularly preferred embodiments.
  • the biological property of the proteins is hereby understood as the change in the contact angle already described by at least 20 °, preferably at least 25 °, particularly preferably at least 30 °, 40 °, 45 °, in particular 50 °.
  • Particularly suitable derivatives for carrying out the present invention are from yaad-Xa-dewA-his (SEQ ID NO: 20), yaad-Xa-rodA-his (SEQ ID NO: 22) or yaad-Xa-basfl-his (SEQ ID NO: 24) derivatives derived from truncation of the yaad fusion partner. Instead of the complete yaad fusion partner (SEQ ID NO: 16) with
  • 294 amino acids can advantageously be used a shortened yaad residue.
  • the truncated residue should comprise at least 20, preferably at least 35, amino acids.
  • a truncated radical having 20 to 293, preferably 25 to 250, particularly preferably 35 to 150 and for example 35 to 100 amino acids can be used.
  • An example of such a protein is yaad40-Xa-dewA-his
  • a cleavage site between the hydrophobin and the fusion partner or the fusion partners can be used to cleave off the fusion partner and release the pure hydrophobin in underivatized form (for example, by BrCN cleavage of methionine, factor Xa, enterokinase, thrombin, TEV cleavage Etc.).
  • hydrophobins used according to the invention as penetration enhancers can be prepared chemically by known methods of peptide synthesis, such as, for example, by Merrifield solid-phase synthesis.
  • Naturally occurring hydrophobins can be isolated from natural sources by suitable methods. As an example, let Wösten et. al., Eur. J Cell Bio. 63, 122-129 (1994) or WO 96/41882 (page 23, line 15 to page 24, line 8).
  • a genetic engineering preparation for hydrophobins without fusion partner from Talaromyces thermophilus is described in US 2006/0040349 (paragraphs [0071] to [0090]).
  • the production of fusion proteins can preferably be carried out by genetic engineering methods in which a nucleic acid sequence coding for the fusion partner and a hydrophobin part, in particular DNA sequence, are combined in such a way that the desired protein is produced in a host organism by gene expression of the combined nucleic acid sequence.
  • the fusion hydrophobins produced by the host organisms by the genetic engineering process can be worked up in a manner known in principle and purified by known chromatographic methods.
  • the fermented cells are first separated from the Fermetationsbrühe, digested and the cell debris of the inclusion bodies (inclusion bodies) separately.
  • inclusion bodies for example by acids, bases and / or
  • Detergents are digested in a manner known in principle in order to release the fusion hydrophobins.
  • the inclusion bodies with the fusion hydrophobins used according to the invention can generally be completely dissolved within about 1 h already using 0.1 M NaOH.
  • the solutions obtained can -ggf. after adjusting the desired pH without further purification, may be used to practice this invention.
  • the fusion hydrophobins can also be isolated from the solutions as a solid. The isolation can preferably be carried out by means of spray granulation or spray drying, as described in WO 2006/082253, (page 11, line 35 to page 12, line 21).
  • the products obtained by the simplified work-up and purification process comprise, in addition to residues of cell debris, usually about 80 to 90% by weight of proteins.
  • the amount of fusion hydrophobins is generally from 30 to 80% by weight with respect to the amount of all proteins.
  • the isolated products containing fusion hydrophobins can be stored as solids and dissolved for use in the respective desired media.
  • the fusion hydrophobins can be used as "pure" hydrophobins for the practice of this invention. Cleavage is advantageously carried out after isolation of the inclusion bodies and their dissolution. According to the invention, the hydrophobins are used as penetration enhancers.
  • hydrophobin is used in combination with at least one further penetration enhancer, wherein at least one further penetration enhancer is selected from the group: DMSO, SDS (Sodium
  • Dodecyl sulfates dimethylformamide, N-methylformamide monohydric or polyhydric alcohols such as ethanol, 1,2 propanediol or benzyl alcohol, saturated and unsaturated fatty alcohols having 8 to 10 carbon atoms such as lauryl alcohol or cetyl alcohol, hydrocarbons such as mineral oil, alkanes, esters, azone, such as 1 Dodecylazacycloheptan-2-one, propylene glycol, chitosan, saturated and unsaturated fatty acids such as stearic acid or oleic acid, fatty acid esters of up to 24 carbon atoms or dicarboxylic acid diesters of up to 24 carbon atoms such as the methyl esters, ethyl esters, isopropyl esters, butyl esters, sec-butyl esters, isobutyl esters, tert-butyl Butyl esters or monoglyceric acid esters of acetic acid, ca
  • hydrophobin is used as a PentrationsverEntr in combination with DMSO or polyglycol.
  • hydrophobin is used as a penetration enhancer in combination with at least one other penetration enhancer in leather care and leather processing.
  • hydrophobin is used as a penetration enhancer for acids and bases, for example carboxylic acids or ammonia, buffer systems, polymers, inorganic particles such as SiO 2 or silicates, colorants such as dyes, fragrances or biocides in combination with at least one further penetration enhancer in leather care and leatherworking used.
  • acids and bases for example carboxylic acids or ammonia, buffer systems, polymers, inorganic particles such as SiO 2 or silicates, colorants such as dyes, fragrances or biocides in combination with at least one further penetration enhancer in leather care and leatherworking used.
  • penetration is enhanced by a phase boundary.
  • the penetration of active ingredients is thereby promoted.
  • active substances are to be understood as meaning all substances having a pharmaceutical or biological action.
  • Active ingredients are thus compounds selected from the group consisting of pharmaceutically active Compounds, therapeutically active compounds and biologically active compounds, cosmetically active compounds, substance for supporting a cosmetic claim (for marketing purposes) such as pearl protein, which qualitatively and / or quantitatively influence biochemical and / or physiological processes in an organism, that is, promote, or at all first enable or inhibit.
  • an organism is selected from the group consisting of individual individuals selected from the realm of protists, bacteria, fungi, plants or animals and parts thereof, such as cells and cell tissues.
  • an organism is a dead organism or parts thereof, such as skin for the production of leather.
  • the enhancement of penetration of the drug compared to the control can be 0.5; 0.6; 0.7, 0.9 or 1%.
  • an enhancement of the penetration by 2,3,4,5,6,7,8,9 or 10% particularly advantageous is an enhancement of the penetration by 1 1, 12,13,14 or 15%, is very particularly advantageous an increase in penetration by 16,17,18,19 or 20% or more%.
  • Another object of the present invention is the use of hydrophobin for the preparation of an agent for improved uptake of active ingredients in topical application.
  • hydrophobin is thus used in a process for the preparation of semi-solid dosage forms or cosmetic preparations selected from the group consisting of ointment, cream, gel and paste.
  • the semisolid dosage forms are prepared as described, for example, in "Arzneiformleehre” by Ursula Schöffling, 4th edition, Deutsche maschiner Verlag, 2003, pages 353 to 392.
  • the preparations contain hydrophobin in a proportion selected from the group consisting of 0.000001 to 10% by weight, 0.0001 to 10% by weight, 0.001 to 10% by weight, 0.01 to 10 wt .-% 0.1 to 10 wt .-% and 1 to 10 wt .-%, and active ingredients in a proportion selected from the group consisting of 0,000001 to 10 wt .-%, 0.0001 to 10 wt %, 0.001 to 10% by weight, 0.01 to 10% by weight 0.1 to 10% by weight and 1 to 10% by weight
  • hydrophobin as a penetration enhancer is in the preparation of agents for therapeutic or prophylactic use in certain diseases of the skin and mucous membranes. Areas of application for this are in particular: viral diseases (for example herpes, coxsackie, varicella zoster, cytomegalovirus etc)
  • bacterial diseases e.g., TB, syphilis, etc.
  • fungal diseases e.g., Candida, Cryptococcus, Histoplasmosis, Aspergillus, Mucormycosis, etc.
  • - tumors e.g., melanomas, adenomas, etc.
  • autoimmune diseases e.g., PEMPHIGUS VULGARIS, BULLOUS PEMPHI-GOID, SYSTEMIC LUPUS ERYTHEMATOSIS, etc.
  • parasitic infestation e.g., ticks, mites, fleas, etc.
  • the preparations for the abovementioned applications are present as aerodispersions, as described, for example, in "Arzneiformleehre” by Ursula Schöffling, 4th edition, Deutsche maschiner Verlag, 2003, Pages 336 to 352.
  • the preparations for the abovementioned applications are present as release systems, selected from the group consisting of nanaoparticles, nanosuspensions, liposomes, microemulsions and bioadhesive preparation forms, as described, for example, in "Arzneiformleehre” by Ursula Schöffling, 4th edition, German maschiner Verlag, 2003, pages 468-471.
  • the preparations contain hydrophobin in a proportion selected from the group consisting of 0.000001 to 10% by weight, 0.0001 to 10% by weight, 0.001 to 10% by weight, 0.01 to 10% by weight. 0.1 to 10 wt .-% and 1 to 10 wt .-%, and active ingredients in a proportion selected from the group consisting of 0.000001 to 10 wt .-%, 0.0001 to 10 wt .-%, 0.001 to 10 wt .-%, 0.01 to 10 wt .-%, 0.1 to 10 wt .-% and 1 to 10 wt .-% ????.
  • hydrophobin as a penetration enhancer is in the preparation of membranes, matrix or patch containing active ingredients, e.g. selected from the group consist of transdermal therapeutic systems TTS.
  • active ingredients in a proportion selected from the group consisting of 0.000001 to 30 wt .-%, 0.0001 to 30 wt .-%, 0.001 to 30 wt .-%, 0.01 to 30 wt. %, 0.1 to 30 wt .-%, 1 to 30 wt .-% and 0.1 to 50 wt .-%, 1 to 50 wt .-%.
  • hydrophobin as a penetration enhancer is in the production of cosmetic preparations.
  • these are hair cosmetic, skin cosmetic or dental cosmetic preparations.
  • effector molecules can be used as active ingredients in the preparations or compositions according to the invention.
  • effector molecule refers to molecules which have a certain, predictable effect. These can be either proteinaceous molecules, such as enzymes or else non-proteinogenic molecules such as dyes, light stabilizers, vitamins and fatty acids, or metal ion-containing compounds.
  • enzymes peptides and antibodies are preferred.
  • oxidases peroxidases, proteases, tyrosinases, metal-binding enzymes, lactoperoxidase, lysozyme, amyloglycosidase, glucose oxidase, superoxide dismutase, photolyase, calalase.
  • Hydrolysates of proteins from plant and animal sources for example hydrolyzates of proteins of marine origin or silk hydrolysates, are also very suitable as proteinaceous effector molecules.
  • peptides used for anti-aging such as Matrixyl (INCI name glycerol-water-butylene glycol-carbomer-polysorbate 20-palmitoyl pentapeptide-4), Argireline (INCI name Aqua, Acety-hexapeptide-3) , Rigin (INCI Name Water (and) Glycerol (and) Steareth-20 (and) Palmitoyl Tetrapeptide-7, Eyeliss (INCI Name Water-Glycerol-Hespiridine Methyl Chalcone-Steareth-20-Dipeptide-2-Palmitoyl Tetrapeptide-7) Regu -Age (INCI name Oxido Reductases-Soy Peptides- Hydrilyzed Rice Bran Extract) and Melanostatin-5 (INCI name aqua-dextran nonapetide-1).
  • Matrixyl INCI name glycerol-water-butylene glycol-carbomer-polysorbate
  • dyes such as semi-permanent dyes or oxidation dyes are preferred.
  • Suitable dyestuffs are all customary hair dyestuffs for the molecules according to the invention. Suitable dyes are the expert from manuals of cosmetics such as Schrader, bases and formulations of cosmetics, Weghig Verlag, Heidelberg, 1989, ISBN 3-7785-1491-1 known.
  • antioxidants are preferred as effector molecules. Antioxidants, also referred to as radical scavengers, are capable of neutralizing so-called free radicals. These are aggressive compounds that arise physiologically in numerous metabolic processes and energy production. They are important for defense reactions of the body, but can also cause damage to the genetic material (DNA), the cell membranes and body whites.
  • Antioxidants include carotenoids ascorbic acid (vitamin C, E 300) as well as sodium L-ascorbate (E 301) and calcium L-ascorbate (E 302); Ascorbyl palmitate (E 304); Butylhydroxyanisole (E 320); Butylhydroxytoluene (E 321); Calcium disodium EDTA (E 385); Gallate as well as propyl gallate (E 310), octyl gallate (E 31 1) and dodecyl gallate
  • At least one compound from the above-mentioned group of antioxidants is selected as antioxidants.
  • carotinoids are to be understood as meaning the following compounds: beta-carotene, lycopene, lutein, astaxanthin, zeaxanthin, cryptoxanthin, citranaxanthin, canthaxanthin, bixin, beta-apo-4-carotenal, beta-apo-8-carotenal, beta-apo-8 -carotinklareester, individually or as Mixture.
  • Preferably used carotenoids are beta-carotene, lycopene, lutein, astaxanthin, zeaxanthin, citranaxanthin and canthaxanthin.
  • retinoids include vitamin A alcohol (retinol) and its derivatives such as vitamin A aldehyde (retinal), vitamin A acid (retinoic acid) and vitamin A esters (for example retinyl acetate, retinyl propionate and
  • retinoic acid encompasses both all-trans retinoic acid and 13-cis retinoic acid.
  • retinol and retinal preferably include the all-trans compounds.
  • the preferred retinoid used for the suspensions of the invention all-trans-retinol, hereinafter referred to as retinol.
  • effector molecules are vitamins, especially vitamin A and their esters.
  • Vitamins are essential organic compounds which are either not synthesized in the animal and human organism or only in insufficient quantities. Because of this definition, 13 components or groups of
  • the fat-soluble vitamins include vitamin A (retinol), vitamin D (calciferols), vitamin E (tocopherols, tocotrienols) and vitamin K (phylloquinone).
  • the water-soluble vitamins include vitamin B 1 (thiamine), vitamin B 2 (riboflavin), vitamin B 6 (pyridoxal), vitamin B 12 (cobalamins), vitamin C (L-ascorbic acid), pantothenic acid, biotin, folic acid and niacin.
  • Vitamins, provitamins and vitamin precursors from groups A, C, E and F in particular 3,4-didehydroretinol, beta-carotene (provitamin of vitamin A), ascorbic acid (vitamin C), and the palmitic acid esters, glucosides or phosphates of ascorbic acid, tocopherols , in particular a-tocopherol and its esters, eg the acetate, nicotinate, phosphate and succinate; vitamin F, which is understood as meaning essential fatty acids, especially linoleic acid, linolenic acid and arachidonic acid;
  • Vitamin E is a collective term for a group of (to date) eight fat-soluble substances with antioxidant and non-antioxidant effects. Vitamin E is part of all membranes of animal cells, but is formed only by photosynthetically active organisms such as plants and cyanobacteria. Four of the eight known forms of vitamin E are called tocopherols (alpha-tocopherol, beta-tocopherol, gamma-tocopherol and delta-tocopherol).
  • tocotrienols alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol and delta-tocotrienol
  • derivatives of these substances such as alpha-tocopheryl acetate may also be advantageous.
  • Vitamin A and its derivatives and provitamins advantageously show a particular skin-smoothing effect.
  • the vitamins, provitamins or vitamin precursors of the vitamin B group or derivatives thereof which are preferably to be used according to the invention and the derivatives of 2-furanone include, inter alia:
  • Trivial name thiamine, chemical name 3 - [(4'-amino-2'-methyl-5'-pyrimidinyl) methyl] -5- (2-hydroxyethyl) -4-methylthiazolium chloride.
  • Vitamin B2 common name riboflavin, chemical name 7,8-dimethyl-10- (1-D-ribityl) -benzo [g] pteridine-2,4 (3H, 10H) -dione.
  • riboflavin z As in whey, other riboflavin derivatives can be isolated from bacteria and yeasts.
  • a stereoisomer of riboflavin which is also suitable according to the invention is lyxoflavin which can be isolated from fishmeal or liver and carries a D-arabityl residue instead of D-ribityl.
  • Vitamin B3 Under this name, the compounds nicotinic acid and nicotinamide (niacinamide) are often performed. According to the invention, the nicotinic acid amide is preferred. Vitamin B5 (pantothenic acid and panthenol). Panthenol is preferably used.
  • panthenol which can be used according to the invention are, in particular, the esters and ethers of panthenol and also cationically derivatized panthenols.
  • derivatives of 2-furanone it is also possible to use derivatives of 2-furanone in addition to pantothenic acid or panthenol.
  • Particularly preferred derivatives are the commercially available substances dihydro-3-hydroxy-4,4-dimethyl-2 (3H) -furanone with the trivial name pantolactone (Merck), 4 hydroxymethyl-g-butyrolactone (Merck), 3,3-dimethyl 2-hydroxy-g-butyrolactone (Aldrich) and 2,5-dihydro-5-methoxy-2-furanone (Merck), expressly including all stereoisomers.
  • Vitamin Bg which is not a uniform substance, but among the
  • Vitamin B7 also known as vitamin H or "skin vitamin”.
  • Biotin is (3aS, 4S, 6aR) -2-oxohexahydrothienol [3,4-d] imidazole-4-valeric acid.
  • Panthenol, pantolactone, nicotinamide and biotin are very particularly preferred according to the invention.
  • suitable derivatives can be used.
  • oil-soluble antioxidants from this group are tocopherol and its derivatives, gallic acid esters, flavonoids and carotenoids as well Butylhydroxytoluene / anisole preferred.
  • water-soluble antioxidants are amino acids, eg. As tyrosine and cysteine and their derivatives and tanning agents, especially those of plant origin are preferred.
  • Triterpenes in particular triterpenic acids such as ursolic acid, rosmarinic acid, betulinic acid, boswellic acid and bryonic acid.
  • Further preferred effector molecules are, preferably low-dose, fruit acids (alpha hydroxy acids) such as malic acid, citric acid, lactic acid, tartaric acid, glycolic acid.
  • fruit acids alpha hydroxy acids
  • At least one compound from the above-mentioned group of fruit acids is selected as effector molecules.
  • concentrations 0.1% to 35%, preferably 0.1% to 10%, in particular 1% to 10%, 1% to 5%.
  • Further preferred effector molecules are urea and derivatives thereof. These can be present in concentrations of 0.1% to 25%, preferably 0.1% to 10%, in particular 1% to 10%, 1% to 5%.
  • the effector molecules are linked to the hydrophobin polypeptide sequence.
  • the effector molecules are linked to a hydrophobin polypeptide sequence.
  • the linkage between effector molecules and hydrophobin polypeptide sequence can be both covalent and ionic or van der Waals interactions.
  • linkage can also be via a so-called linker, i. an at least bifunctional molecule which binds with a function of the hydrophobin polypeptide sequence and is linked to another function of the effector molecule.
  • effector molecule also consists of a polypeptide sequence
  • linking of effector molecules and hydrophobin polypeptide sequence can be effected by a so-called fusion protein, ie a continuous polypeptide sequence consists of the two partial sequences ie effector molecules and hydrophobin polypeptide sequence.
  • spacer elements between effector molecules and hydrophobin polypeptide sequence, for example polypeptide sequences which have a potential cleavage site for a protease, lipase, esterase, phosphatase, hydrolase or polypeptide sequences which permit easy purification of the fusion protein, for example so-called histates ie Oligohistidinreste.
  • the linkage in the case of a non-proteinaceous effector molecule with the hydrophobin polypeptide sequence is preferably carried out by functionalizable groups (side groups) on the hydrophobin polypeptide, which form a covalent bond with a chemical function of the effector molecule.
  • Another preferred linkage of the hydrophobin polypeptide sequence with an effector molecule is the use of a tailor-made linker.
  • a linker has two or more so-called anchor groups with which it can link the hydrophobin polypeptide sequence and one or more effector molecules.
  • an anchor group for hydrophobin peptide may be a thiol function by which the linker can enter into a disulfide bond with a cysteine residue of the hydrophobin polypeptide.
  • An anchor group for the effector molecule can be, for example, a carboxyl function, by means of which the linker can enter into an ester bond with a hydroxyl function of the effector molecule.
  • linker allows the exact adaptation of the linkage to the desired effector molecule.
  • the linker used depends on the functionality to be coupled. Suitable are e.g. Molecules coupling to hydrophobin polypeptides via sulfhydryl reactive groups, e.g. Maleimides, Pydridyldisulfide, alpha -Haloacetyle, vinylsulfone and to effector molecules by means
  • Sulfhydryl-reactive groups e.g. Maleimides, pydridyl disulfides, alpha-haloacetyls, vinyl sulfones
  • amine-reactive groups e.g., succinimidyl esters, carbodiimde, hydroxymethyl phosphine, imidoesters, PFP esters, etc.
  • Sugars or oxidized sugar-reactive groups eg hydrazides etc.
  • carboxy-reactive groups eg carbodiimides etc.
  • Hydroxyl-reactive groups eg isocyanates etc.
  • thymine-reactive groups eg psoralen etc.
  • unselective groups eg arylazides etc.
  • photoactivatable groups eg perfluorophenyl azide etc.
  • metal-complexing groups eg EDTA, hexahis, ferritin
  • Antibodies and fragments e.g., single-chain antibodies, F (ab) fragments of antibodies, catalytic antibodies.
  • a direct coupling between active / effect substance and the keratin binding domain can be e.g. by means of carbodiimides, glutaric dialdehyde or other crosslinkers known to the person skilled in the art.
  • the linker may be stable, thermo gapable, photocleavable or enzymatically cleavable (especially by lipases, esterases, proteases, phosphatases, hydrolases, etc.). Corresponding chemical structures are known to the person skilled in the art and are integrated between the molecular parts. Examples of enzymatically cleavable linkers which can be used in the molecules according to the invention are mentioned, for example, in WO 98/01406 (page 3, line 30 to page 23, line 9), to the entire contents of which reference is hereby expressly made.
  • the preparations are preferably used for skin, nail, dental and hair cosmetics. They allow a high concentration and long duration of action of skin, nail, tooth and hair care or skin, nail, tooth and hair protecting effector.
  • auxiliaries and additives for the production of hair cosmetic, dental cosmetic or skin cosmetic preparations are familiar to the expert and can from manuals of cosmetics, such as Schrader, bases and formulations of cosmetics, Weghig Verlag, Heidelberg, 1989, ISBN 3-7785-1491-1 be removed.
  • this hair cosmetic or skin or tooth cosmetic preparation is for the care or protection of the skin or hair or teeth and is in the form of an emulsion, a dispersion, a suspension, an aqueous surfactant preparation, a milk, a lotion, a cream, a balm, ointment, gel, granules, powder, stick preparation, such as a lipstick, foam, aerosol or spray.
  • emulsions Oil-in-water emulsions (O / W type) and water-in-oil emulsions (W / O type) or microemulsions in question.
  • Topical preparations are to be understood as meaning those preparations which are suitable for applying the active ingredients to the skin in fine distribution and preferably in a form absorbable by the skin.
  • Topical preparations e.g. aqueous and aqueous-alcoholic solutions, sprays, foams, foam aerosols, ointments, aqueous gels, emulsions of the O / W or W / O type, microemulsions or cosmetic stick preparations.
  • the agent contains a carrier.
  • a carrier is water, a gas, a water-based liquid, an oil, a gel, an emulsion or microemulsion, a dispersion or a mixture thereof.
  • the mentioned carriers show good skin tolerance.
  • Particularly advantageous for topical preparations are aqueous gels, emulsions or microemulsions.
  • Nonionic surfactants, zwitterionic surfactants, ampholytic surfactants or anionic emulsifiers can be used as emulsifiers.
  • the emulsifiers may be present in the composition according to the invention in amounts of 0.1 to 10, preferably 1 to 5 wt .-%, based on the composition.
  • a surfactant of at least one of the following groups may be used:
  • Alkyl mono- and oligoglycosides having 8 to 22 carbon atoms in the alkyl radical and their ethoxylated analogs
  • Polyol and in particular polyglycerol esters such as Polyglycerinpolyricinoleat, Polygl ycerinpoly-12-hydroxystearate or Polyglycerindimerat. Also suitable are mixtures of compounds of several of these classes of substances; Addition products of 2 to 15 moles of ethylene oxide with castor oil and / or hydrogenated castor oil;
  • Partial ester based on linear, branched, unsaturated or saturated Cg / 22 -
  • Fatty acids Fatty acids, ricinoleic acid and 12-hydroxystearic acid and glycerol, polyglycerol, pentaerythritol, dipentaerythritol, sugar alcohols (eg sorbitol), alkyl glucosides (e.g., methyl glucoside, butyl glucoside, lauryl glucoside) and polyglucosides (e.g., cellulose);
  • alkyl glucosides e.g., methyl glucoside, butyl glucoside, lauryl glucoside
  • polyglucosides e.g., cellulose
  • zwitterionic surfactants can be used as emulsifiers.
  • Zwitterionic surfactants are surface-active compounds which carry at least one quaternary ammonium group and at least one carboxylate or sulfonate group in the molecule.
  • Particularly suitable zwitterionic surfactants are the so-called betaines, such as N-alkyl-N, N-dimethylammonium glycinates, for example cocoalkyldimethylammonium glycinate, N-acylamino-propyl-N, N-dimethylammonium glycinates, for example cocoacylaminopropyldimethylammonium glycinate, and 2-alkyl-3-ol Carboxylmethyl-3-hydroxyethylimidazoline having in each case 8 to 18 carbon atoms in the alkyl or acyl group and Kokosacylaminoethylhydroxyethyl carboxymethylglycinat.
  • Particularly preferred is the known under the CTFA name Cocamidopropyl Betaine fatty acid amide derivative.
  • ampholytic surfactants are to be understood as meaning those surface-active compounds which, apart from a C ⁇ j S'A'ky '' or acyl group in the molecule, contain at least one free amino group and at least one -COOH or -S ⁇ 3H group and which form internal
  • Salts are capable.
  • suitable ampholytic surfactants are N-alkylglycines, N-alkylpropionic acids, N-alkylamino-butanoic acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamido-propylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids each having about 8 to 18 C atoms in the alkyl group.
  • ampholytic surfactants are N-cocoalkyl aminopropionate, aminopropionate and C
  • ampholytic quaternary emulsifiers those of the esterquat type, preferably methyl-quaternized difatty acid triethanolamine ester salts, being particularly preferred.
  • alkyl ether sulfates, monoglyceride sulfates, fatty acid sulfates, sulfosuccinates and / or ether carboxylic acids can be used as anionic emulsifiers.
  • Guerbet carbonates esters of benzoic acid with linear and / or branched Cg-C22 "alcohols (eg Finsolv 1 - 1 TN), dialkyl ethers, ring-opening products of epoxidized fatty acid esters with polyols, silicone oils and / or aliphatic or naphthenic hydrocarbons into consideration
  • Silicone compounds are also used, for example dimethylpolysiloxanes, methylphenylpolysiloxanes, cyclic silicones and amino-, fatty acid-, alcohol-, polyether-, epoxy-, fluorine-, alkyl- and / or glycoside-modified silicone compounds which may be both liquid and resinous at room temperature.
  • the oil bodies may be present in the compositions according to the invention in amounts of from 1 to 90, preferably from 5 to 80, and in particular from 10 to 50,% by weight, based on the composition.
  • Suitable effector molecules ii: perfume oils, cyclodextrins, ion exchangers, zinc ricinoleate, antimicrobial / bacteriostatic compounds (e.g., DCMX, Irgasan DP 300, TCC).
  • Suitable antiperspirants are: tannins, and zinc / aluminum salts.
  • the preparations contain, in addition to the auxiliaries described hydrophobin in a proportion selected from the group consisting of 0.000001 to 10 wt .-%, 0.0001 to 10 wt .-%, 0.001 to 10 wt .-%, 0.01 to 10 Wt .-%, 0.1 to 10 wt .-% and 1 to 10 wt .-%,
  • hydrophobin is used as a penetration enhancer in crop protection products.
  • the present invention furthermore relates to a process for the preparation of crop protection agents containing hydrophobin and crop protection agents containing hydrophobin.
  • the crop protection agents contain hydrophobin in a proportion selected from the group consisting of 0.000001 to 10% by weight, 0.0001 to 10% by weight, 0.001 to 10% by weight, 0.01 to 10 Wt .-%, 0.1 to 10 wt .-% and 1 to 10 wt .-%,
  • the content of active and / or effect material can be varied over a wide range.
  • the amphiphilic polymer compositions make it possible to produce so-called active substance concentrates containing the active ingredient in an amount of at least 5% by weight, eg. B. in an amount of 5 to 50 wt .-% and in particular in an amount of 5 to 20 wt .-%, based on the total weight of the composition.
  • the aqueous active compound compositions according to the invention can be formulated solvent-free or low-solvent, ie. H. the proportion of organic solvents in the aqueous active ingredient composition is frequently not more than 10% by weight, in particular not more than 5% by weight and in particular not more than 1% by weight, based on the total weight of the composition.
  • aqueous compositions of the invention a variety of different agents and effect substances can be formulated.
  • a particular embodiment of the invention relates to the formulation of active ingredients for crop protection, i. of herbicides, fungicides, nematicides, acaricides, insecticides and plant growth regulators.
  • fungicidal active compounds that can be formulated as the aqueous active substance composition according to the invention include:
  • acylalanines such as benalaxyl, metalaxyl, ofurace, oxadixyl
  • ⁇ amine derivatives such as aldimorph, dodine, dodemorph, fenpropimorph, fenpropidin, guazatine, iminoctadine, spiroxamine, tridemorph
  • antibiotics such as cycloheximide, griseofulvin, kasugamycin, natamycin, polyoxine and streptomycin
  • ⁇ azoles such as bitertanol, bromoconazole, cyproconazole, difenoconazole, dinitroconazole, epoxiconazole, fenbuconazole, fluquiconazole, flusilazole, flutriafol, hexaconazole, imazalil, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prochloraz, Prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimol, triflumizole, triticonazole;
  • Dithiocarbamates such as Ferbam, Nabam, Maneb, Mancozeb, Metam, Metiram, Propineb, Polycarbamate, Thiram, Ziram, Zineb;
  • Heterocyclic compounds such as anilazine, benomyl, boscalid, carbendazim, carboxin, oxycarboxine, cyazofamide, dazomet, dithianone, famoxadone, fenamidone, fenarimol, fuberidazole, flutolanil, furametpyr, isoprothiolanes, mepronil, nuarimol, picobezamide, probenazoles, proquinazide, pyrifenox, pyroquilone, quinoxyfen , Silthiofam; Thiabendazoles, thifluzamide, thiophanate-methyl, tiadinil, tricyclazoles, triforins;
  • Nitrophenyl derivatives such as binapacryl, dinocap, dinobutone, nitrophthalic-isopropyl;
  • phenylpyrroles such as fenpiclonil and fludioxonil
  • ⁇ unclassified fungicides such as acibenzolar-S-methyl, benthiavalicarb
  • Carpropamide chlorothalonil, cyflufenamid, cymoxanil, diclomethine, diclocymet, diethofencarb, edifenphos, ethaboxam, fenhexamide, fentin acetate, fenoxanil, ferimzone, fluazinam, fosetyl, fosetyl-aluminum, iprovalicarb, hexachlorobenzene, metrafenone, pencycuron, propamocarb, phthalides, toloclofos- Methyl, quintozene, zoxamide;
  • ⁇ strobilurins such as those described in WO 03/075663 by the general formula I, such as azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin and trifloxystrobin;
  • Sulfenic acid derivatives such as captafol, captan, dichlofluanid, folpet, tolylfluanid; ⁇ cinnamic acid and analogs such as dimethomorph, flumetover, flumorp;
  • ⁇ 6-aryl- [1,2,4] triazolo [1,5-a] pyrimidines as described, for example, in WO 98/46608, WO 99/41255 or WO 03/004465 (in each case by the general formula I (p 1, line 8 to page 11, line 45, and compounds shown in formula IA in conjunction with tables 1 to 44 and table WO 03/00465) ⁇ amide fungicides such as cyclofenamide and (Z) -N- [ ⁇ - (cyclopropylmethoxyimino) -2,3-difluoro-6- (difluoromethoxy) benzyl] -2-phenylacetamide.
  • ⁇ amide fungicides such as cyclofenamide and (Z) -N- [ ⁇ - (cyclopropylmethoxyimino) -2,3-difluoro-6- (difluoromethoxy) benzyl] -2-phenylacetamide.
  • ⁇ 1, 3,4-thiadiazoles such as buthidazole and cyprazole
  • Amides such as allidochlor, benzoylpropyl, bromobutide, chlorthiamide, dimepiperate, dimethenamid, diphenamid, etobenzanide, flampropmethyl, fosamine, isoxaben, Metazachlor, Alachlor, Acetochlor, Metolachlor, Monalide, Naptalame, Pronamid, Propanil;
  • aminophosphoric acids such as bilanafos, buminafos, glufosinate-ammonium, glyphosate, sulfosates; ⁇ aminotriazoles such as amitrole, anilides such as anilofos, mefenacet;
  • aryloxyalkanoic acid such as 2,4-D, 2,4-DB, Clomeprop, dichlorprop, dichlorprop-P, dichlorprop-P, fenoprop, fluroxypyr, MCPA, MCPB, mecoprop, mecoprop-P, napropamide, napro-panilide, triclopyr ;
  • Benzoic acids such as Chloramben, Dicamba; Benzothiadiazinones, such as bentazone;
  • Bleachers such as Clomazone, Diflufenican, Fluorochloridone, Flupoxam, Fluridone, Pyrazolate, Sulcotrione;
  • Carbamates such as carbetamide, chlorobufam, chloropram, desmedipham, phenmedipham, vernolates; ⁇ quinolinic acids such as quinclorac, quinmerac;
  • dihydrobenzofurans such as ethofumesates
  • Dihydrofuran-3-one such as flurtamone
  • Dinitroanilines such as benefin, butraline, dinitramine, ethalfluralin, fluchloralin, isopropalin, nitralin, oryzalin, pendimethalin, prodiamines, profluralin, trifluralin, dinitrophenols such as bromofenoxime, dinoseb, dinoseb acetate, dinoterb, DNOC, minoterb acetate;
  • ⁇ diphenyl ethers such as acifluorfen-sodium, aclonifen, bifenox, chloronitrofen, difenoxuron, ethoxyfen, fluorodifen, fluoroglycofen-ethyl, fomesafen, furyloxyfen, lactofen, nitrofen, nitrofluorfen, oxyfluorfen;
  • ⁇ imidazoles such as isocarbamide
  • Imidazolinones such as imazamethapyr, imazapyr, imazaquin, imazethabenz-methyl, imazethapyr, imazapic, imazamox; ⁇ oxadiazoles such as methazoles, oxadiargyl, oxadiazon; Oxiranes such as tridiphanes;
  • ⁇ phenols such as bromoxynil, loxynil;
  • phenoxyphenoxypropionic esters such as clodinafop, cyhalofop-butyl, Diclofop- methyl, fenoxaprop-ethyl, fenoxaprop-p-ethyl, Fenthiapropethyl, fluazifop-butyl, Fluazifop-p-butyl, haloxy-pent-ethoxy-ethyl, haloxy-pent-methyl, haloxy-stop-p-methyl, isoxapyrifop, propa-quizafop, quizalofop-ethyl, quizalofop-p-ethyl, quizalofop-tefuryl;
  • Phenylacetic acids such as chlorfenac; Phenylpropionic acids such as chlorophenprop-methyl; Ppi agents such as benzofenap, cinidone-ethyl, flumiclorac-pentyl, flumioxazine, flumipropyne, flupropacil, pyrazoxyfen, sulfentrazone, thidiazimine;
  • ⁇ pyridinecarboxylic acids such as clopyralid, dithiopyr, picloram, thiazopyr; ⁇ pyrimidyl ethers such as pyrithiobacic acid, pyrithiobac-sodium, KIH-2023, KIH-6127; Sulfonamides such as flumetsulam, metosulam;
  • ⁇ uracils such as bromacil, lenacil, terbacil;
  • Benazoline Benfuresate, Bensulide, Benzofluor, Bentazone, Butamifos, cafenstrole, Chlorthal-dimethyl, Cin-methylin, Dichlobenil, Endothall, Fluorobentranil,
  • Sulfonylureas such as amidosulfuron, azimsulfuron, bensulfuron-methyl, chlorimuron-ethyl, chlorosulfuron, cinosulfuron, cyclosulfamuron, ethametsulfuron-methyl, flazasulfuron, halosulfuron-methyl, imazosulfuron, metsulfuron-methyl, nicosulfuron, primisulfuron, prosulfuron, pyrazosulfuron-ethyl, rimsulfuron, sulfometuron methyl, thifensulfuron-methyl, triasulfuron, tribenuron-methyl, triflusulfuron-methyl, tritosulfuron;
  • Cyclohexenone-type plant protection agents such as alloxydim, clethodim, cloproxydim, cycloxydim, sethoxydim and tralkoxydim.
  • Very particularly preferred cyclohexenone-type herbicidally active compounds are: Tepraloxydim (compare AGROW, no.
  • organophosphates such as acephates, azinphos-methyl, chlorpyrifos, chlorfenvinphos, diazinon, dichlorvos, dimethylvinphos, dioxabenzofos, dicrotophos, dimethoates, disulphoton, ethion, EPN, fenitrothion, fenthione, isoxathione, malathion,
  • Methamidophos Methidathion, Methyl Parathion, Mevinphos, Monocrotophos, Oxydemeton-methyl, paraoxon, parathion, phenthoate, phosalone, phosmet, phosphamidone, phorates, phoxim, pirimiphos-methyl, profenofos, prothiofos, primiphos-ethyl, pyraclofos, pyridaphenthione, sulprophos, triazophos, trichlorofon; Tetrachlorvinphos, vamidothion ⁇ carbamates such as alanycarb, benfuracarb, bendiocarb, carbaryl, carbofuran,
  • Pyrethroids such as bifenthrin, cyfluthrin, cycloprothrin, cypermethrin, deltamethrin, esfenvalerate, ethofenprox, fenpropathrin, fenvalerate, cyhalothrin, lambda-cyhalothrin, permethrin, silafluofen, tau-fluvalinate, tefluthrin, tralomethrin, alpha-cypermethrin, zeta-cypermethrin, permethrin;
  • Arthropod growth regulators a) chitin synthesis inhibitors eg benzoylureas such as chlorofluorazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron; Buprofezin, diofenolan, hexythiazox, etoxazole, clofentazine; b) ecdysone antagonists such as halofenozides, methoxyfenozides, tebufenozides; c) juvenoids such as pyriproxyfen, methoprene, fenoxycarb; d) lipid biosynthesis inhibitors such as spirodiclofen;
  • chitin synthesis inhibitors eg benzoylureas such as chlorofluorazuron, diflubenzuron, flucyclo
  • Neonicotinoids such as flonicamid, clothianidin, dinotefuran, imidacloprid, thiamethoxam, nitenpyram, nithiazine, acetamiprid, thiacloprid;
  • Other unclassified insecticides such as abamectin, acequinocyl, acetamiprid, amitraz, azadirachtin, bensultap bifenazate, cartap, chlorfenapyr, chlordimeform, cyromazine, diafenthiuron, dinetofuran, diofenolan, emamectin, endosulfan, ethiprole, fenazaquin, fipronil, formetanate, formetanate hydrochloride, gamma-HCH Hydramethylnone, imidacloprid, indoxacarb, isoprocarb, metolcarb, pyrid
  • N-phenylsemicarbazones as described in EP-A 462 456 by the general formula I, in particular compounds of the general formula IV
  • R 1 and R 12 are independently hydrogen, halogen, CN, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl or C 1 -C 4 haloalkoxy and R 13 is C 1 -C 4 alkoxy, C 1 -C 4 Haloalkyl or C1-C4 haloalkoxy, eg compound IV, wherein R1 is 3-CF3 and R2 is 4-CN and R3 is 4-OCF3.
  • Useful growth regulators are, for example, chlormequat chloride, mepiquat chloride, prohexadione calcium or the group of gibberellins.
  • Active ingredient compositions of fungicides in particular strobilurins, azoles and 6-aryltriazolo [1, 5a] pyrimidines, as described e.g. in WO 98/46608, WO 99/41255 or WO 03/004465 are each described by the general formula I (page 1, line 8 to page 11, line 45, and compounds shown in formula IA in conjunction with Tables 1 to 44th and Table A WO 03/00465), in particular for active compounds of the general formula V,
  • Rx is a group NR14R15, or linear or branched C1-C8-alkyl which is optionally substituted by halogen, OH, C1-C4-alkoxy, phenyl or C3-C6-cycloalkyl, C2-C6-alkenyl, C3-C6- Cycloalkyl, C3-C6-cycloalkenyl, phenyl or naphthyl, wherein the last 4 mentioned radicals 1, 2, 3 or 4 substituents selected from halogen, OH, C1-C4-alkyl, C1-C4-haloalkoxy, C1-C4-alkoxy and C1-C4 may have haloalkyl;
  • R 14, R 15 independently of one another are hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -haloalkyl, C 3 -C 10 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 2 -C 8 -alkenyl, C 4 -C 10 -alkadienyl, C 2 -C 8 -haloalkenyl, C 3 -C 6 -cycloalkenyl, C 2 -C 8 -halocycloalkenyl, C 2 -C 8 -alkynyl, C 2 -C 8 -haloalkynyl or C 3 -C 6 -cycloalkynyl,
  • R 14 and R 15 together with the nitrogen atom to which they are attached are five- to eight-membered heterocyclyl which is bonded via N and contains one, two or three further heteroatoms from the group O, N and S as ring member and / or one or more Substituents from the group halogen, C1-C6-alkyl, C1-C6- Haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 3 -C 6 -alkenyloxy, C 3 -C 6 -haloalkenyloxy, (exo) -Cl-C 6 -alkylene and oxyalkylene Can carry C1-C3-alkyleneoxy;
  • L is selected from halo, cyano, C 1 -C 6 alkyl, C 1 -C 4 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 4 haloalkoxy and C 1 -C 6 alkoxycarbonyl;
  • L1 is halogen, C1-C6-alkyl or C1-C6-haloalkyl and especially fluorine or chlorine;
  • X represents halogen, C 1 -C 4 -alkyl, cyano, C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkyl and preferably represents halogen or methyl and in particular denotes chlorine.
  • Examples of compounds of formula V are 5-chloro-7- (4-methylpiperidin-1-yl) -6- (2,4,6-trifluorophenyl) - [1,2,4] triazolo [1,5-a] pyrimidine, 5-chloro-7- (4-methylpiperazin-1-yl) -6- (2,4,6-trifluorophenyl) - [1,2,4] triazolo [1,5-a] pyrimidine, 5-chloro -7- (morpholin-1-yl) -6- (2,4,6-trifluorophenyl) - [1, 2,4] triazolo [1,5-a] pyrimidine, 5-chloro-7- (piperidine-1 -yl) -6- (2,4,6-trifluorophenyl) - [1, 2,4] triazolo [1,5-a] pyrimidine, 5-chloro-7- (morpholin-1-yl) -6- ( 2,4,6-trifluorophenyl)
  • hydrophobin as a penetration enhancer for the preparation of aqueous active ingredient compositions of insecticides, in particular arylpyrroles such as chlorfenapyr, pyrethroids such as bifenthrin, cyfluthrin, cycloprothrin, cypermethrin, deltamethrin, esfenvalerates, ethofenprox, fenpropathrin, fenvalerates, cyhalothrin, lambda -Cyhalothrin, permethrin, silafluofen, tau-fluvalinate, tefluthrin, tralomethrin, alpha-cypermethrin, zeta-cypermethrin and permethrin, of neonicotinoids and of semicarbazones of formula IV, of fipronil.
  • arylpyrroles such as chlorfenapyr
  • pyrethroids such as
  • hydrophobin as a penetration enhancer leads to a reduction in the concentration of active ingredients necessary for the desired effect to be achieved by 1%, 2%, 3%, 4%, 5%,%, 7%, 8%. , 9%, 10%, preferably 1 1%, 12%, 13%, 14%, 15%, 16%, 18%, 20%, more preferably 22%, 25% 30%, 35%, 40%, 45 %, 50%, especially 60%, 70%, 80%, 90%.
  • a phosphate-buffered solution is first applied to the surface or phase boundary to be treated. Hydrophobin at a concentration of 0.01 to 0.2 percent by weight is dissolved in 5 mM NaH 2 PO 4 at pH 7.5. After incubation with the hydrophobin solution, the preparation of the preparation containing at least one active ingredient is applied.
  • Another object of the present invention is a method for improved absorption of active ingredients in topical application, characterized in that hydrophobin a) before the active substances or b) is applied simultaneously with the active ingredients.
  • Another object of the present invention is a process for the preparation of an agent for improved uptake of active ingredients in topical application, characterized in that hydrophobin in solid form, in solution or in dispersion in an organic or in an inorganic medium contained in a preparation at least one active ingredient becomes.
  • the background is the consideration that the incubation of the cells with the antioxidative effective reference substances, under the influence of hydrophobin (Hydropobin A (SEQ ID 20 from WO2007 / 14897) or B (SEQ ID 26 from WO2007 / 14897)) as a penetration enhancer to an enhanced antioxidant Potential of leads.
  • hydrophobin Hydrophobin A (SEQ ID 20 from WO2007 / 14897) or B (SEQ ID 26 from WO2007 / 14897)) as a penetration enhancer to an enhanced antioxidant Potential of leads.
  • hydrophobin Hydrophobin
  • the reference substances used were vitamin E (alpha tocopheryl acetate), vitamin C (Mg ascorbyl phosphate) and quercetin.
  • Normal dermal connective tissue cells fibroblasts were used as test cells, since they provided good signal strengths in the evaluation procedure.
  • NHDF cultures normal human dermal fibroblasts
  • the investigations were carried out with these static cultures.
  • the cultures were treated with the test solutions for 24 h.
  • the medium including test solutions
  • the cultures were washed with buffer and incubated with the fluorescent dye (DCFH).
  • DCFH fluorescent dye
  • to remove unabsorbed dye was washed several times and the cells were mixed with the colorless assay medium.
  • the plates with the cells were placed in a fluorescence reader and the measurement started with a preliminary phase without stress.
  • H 2 O 2 multiple intracellular free radicals were subsequently induced, which react with the dye to a fluorescent derivative.
  • the free radicals are previously quenched by antioxidants, the formation of fluorescent derivatives is prevented or reduced.
  • the y-axis represents the oxidative stress in the cells as the fluorescence which is emitted when free radicals react with the intracellular dye DCFH. This means that a lower bar symbolizes low oxidative stress and thus high antioxidant capacity of the cells as a result of supplementation. All fluorescence values were corrected with the protein contents of the cultures after completion of the measurements (determined with Coomassie staining). As a result, fluctuations in the cell number, which would also affect fluctuations in the fluorescence (due to the different amount of dye), compensated. Thus, cell-number-adjusted data is displayed. Tocopheryl acetate alone has no antioxidant potential with the cell line used in the studies carried out.
  • Hydrophobin protein B was improved (H protein B 0.05%, combined with quercetin 0.0006%).
  • Test Variation 1 Preparation of hydrophobin A or B at a concentration of 0.01 to 0.2 weight percent.
  • Solvent is 5 mM NaH 2 PO 4 pH 7.5. To accelerate the solution, it is dissolved by means of a magnetic stirrer at room temperature for 1 h.
  • a comparative suspension is prepared without hydrophobin. Incubate the hair for 1 hour at 32 ° C, then wash with drinking water and dry.
  • hydrophobin A or B Preparation of hydrophobin A or B at a concentration of 0.01 to 0.2 weight percent.
  • Solvent is 5 mM NaH 2 PO 4 pH 7.5. To accelerate the solution, it is dissolved by means of a magnetic stirrer at room temperature for 1 h.
  • a comparative suspension is prepared without hydrophobin.
  • hydrophobin leads to an improved penetration of the lactic acid into the skin, so that hydrophobin serves as a penetration enhancer for this substance.

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Abstract

La présente invention concerne l'utilisation de polypeptides de type hydrophobine comme renforçateurs de pénétration.
EP08803103A 2007-09-13 2008-08-20 Utilisation de polypeptides de type hydrophobine comme renforçateurs de pénétration Withdrawn EP2200651A2 (fr)

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EP13174958.2A EP2676680A1 (fr) 2007-09-13 2008-08-20 Utilisation de polypeptides d'hydrophobine en tant qu'activateurs de pénétration

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Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI0607594A2 (pt) * 2005-03-31 2010-04-06 Basf Ag compósito multi-camadas ou substrato revestido, processo para a preparação dos mesmos, e, uso de hidrofobinas
DE102005033002A1 (de) * 2005-07-14 2007-01-18 Basf Ag Wässrige Monomeremulsionen enthaltend Hydrophobin
JP2012500241A (ja) * 2008-08-18 2012-01-05 ビーエーエスエフ ソシエタス・ヨーロピア ケラチンの非永久的染色のためのハイドロフォビンの使用
EP2342237B1 (fr) * 2008-11-03 2014-04-23 Basf Se Mélanges de photo-initiateurs
US8226967B2 (en) 2008-11-27 2012-07-24 Basf Se Surface active proteins as excipients in solid pharmaceutical formulations
CN102333546B (zh) * 2009-02-26 2014-11-26 Brain生物技术研究与信息网络股份公司 用于在跨角蛋白的局部药物递送中使用表面活性蛋白的组合物、用途和方法
JP2012519767A (ja) * 2009-03-09 2012-08-30 ビーエーエスエフ ソシエタス・ヨーロピア 水相増粘用の水溶性ポリマーとハイドロフォビンの相乗性混合物の利用
US8357382B1 (en) * 2009-04-02 2013-01-22 Hilt Bethany L Cosmetic formulations
FI20095638A0 (fi) * 2009-06-09 2009-06-09 Valtion Teknillinen Hydrofobiineja aktiivisten aineiden dispergointiin
WO2011101457A1 (fr) 2010-02-18 2011-08-25 B.R.A.I.N. Biotechnology Research And Information Network Ag Protéines tensioactives chimères
EP2371844A1 (fr) 2010-03-25 2011-10-05 B.R.A.I.N. Biotechnology Research and Information Network AG Protéines actives à surface chimérique
US8563031B2 (en) * 2010-05-27 2013-10-22 Absize, Inc. Piroxicam-containing matrix patches and methods for the topical treatment of acute and chronic pain and inflammation therewith
US20130202539A1 (en) * 2010-08-12 2013-08-08 Eleanor Margaret D'Agostino Oral care compositions
US8658680B2 (en) 2010-08-17 2014-02-25 Bayer Cropscience Lp Chemically stable dispersions of prothioconazole and processes for preparing them
EP3062889A2 (fr) * 2013-11-01 2016-09-07 Spherium Biomed S.L. Corps d'inclusion pour administration transdermique d'agents thérapeutiques et cosmétiques
EP3214932A1 (fr) * 2014-11-05 2017-09-13 Basf Se Procédé de préparation d'une composition agrochimique de toxicité réduite par broyage d'un pré-mélange de pesticide et d'une hydrophobine
KR101786914B1 (ko) * 2017-01-31 2017-11-15 주식회사 삼양사 피부 리프팅 또는 탄력 개선을 위한 점착성 탄력 밴드
WO2019139380A1 (fr) * 2018-01-10 2019-07-18 주식회사 지투지바이오 Charge de microsphères de polycaprolactone contenant de la vitamine c et son procédé de préparation
CN108530106A (zh) * 2018-06-14 2018-09-14 长沙鹏登生物陶瓷有限公司 一种制备渐变色氧化锆义齿陶瓷坯体的染色液
CN108585845A (zh) * 2018-06-14 2018-09-28 长沙鹏登生物陶瓷有限公司 一种颜色和透性渐变氧化锆义齿陶瓷坯体的制备方法
BR112021025246A2 (pt) * 2019-06-15 2022-01-25 Bayer Ag Formulações estabilizadas de ditiocarbamatos
CN111842088B (zh) * 2020-07-30 2021-08-10 齐鲁工业大学 一种低电位疏水性多肽单层膜及其制备方法与应用

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1165574B (de) 1960-08-08 1964-03-19 Dehydag Gmbh Verfahren zur Herstellung von als Emulgiermittel fuer Salbengrundlagen dienenden Mischestern
DE69119301T2 (de) 1990-06-16 1996-10-17 Nihon Nohyaku Co Ltd Hydrazincarboxamidderivate, Verfahren für ihre Herstellung und ihre Verwendung
DE4210165A1 (de) 1991-07-30 1993-02-04 Schering Ag Transdermale therapeutische systeme
AU5914196A (en) * 1995-06-12 1997-01-09 Proefstation Voor De Champignoncultuur Hydrophobins from edible fungi, genes, nucleotide sequences and dna-fragments encoding for said hydrophobins, and expression thereof
DE19626762A1 (de) 1996-07-03 1998-01-08 Basf Ag Enzymatisch spaltbare Linker für Festphasensynthesen
TW460476B (en) 1997-04-14 2001-10-21 American Cyanamid Co Fungicidal trifluoromethylalkylamino-triazolopyrimidines
EP0897904B1 (fr) 1997-08-20 2002-02-20 Basf Aktiengesellschaft 2-Méthoxybenzophénones fongicides
ES2212527T3 (es) 1998-02-11 2004-07-16 Basf Aktiengesellschaft 7-alquil-triazolopirimidinas fungicidas.
IL145337A0 (en) * 1999-03-25 2002-06-30 Valtion Teknillinen Process for partitioning of proteins
GB0002663D0 (en) 2000-02-04 2000-03-29 Biomade B V Method of stabalizing a hydrophobin-containing solution and a method of coating a surface with a hydrophobin
WO2003000465A2 (fr) 2001-06-25 2003-01-03 Fast Technology Ag Outil dynamometrique electrique
KR100619216B1 (ko) 2001-07-05 2006-09-08 바스프 악티엔게젤샤프트 살진균성 트리아졸로피리미딘, 이의 제조방법 및 유해진균 방제를 위한 이의 용도 및 상기 화합물을 포함하는조성물
FR2833490B1 (fr) 2001-12-14 2004-12-10 Oreal Utilisition cosmetique d'au moins une hydrophobine pour le traitement des matieres keratiniques et compositions mises en oeuvre
PL211515B1 (pl) 2002-03-11 2012-05-31 Basf Ag Sposób uodporniania roślin na bakteriozy i zastosowanie pochodnych benzenu do uodporniania roślin
EP1815846A3 (fr) * 2002-10-11 2008-10-22 Idea Ag Agrégat a capacité de déformation accrue, comprenant au moins trois composants amphipathiques permettant un transport amelioré à travers des barrières semi-permeables, et pour administration non effractive de medicaments in vivo, en particulier par voie transcutanée
US7241734B2 (en) 2004-08-18 2007-07-10 E. I. Du Pont De Nemours And Company Thermophilic hydrophobin proteins and applications for surface modification
JP5250264B2 (ja) * 2005-02-07 2013-07-31 ビーエーエスエフ ソシエタス・ヨーロピア 新規ハイドロフォビン融合タンパク質、その製造および使用
TW200639179A (en) * 2005-02-07 2006-11-16 Basf Ag Method for coating surfaces with hydrophobins
JP5064376B2 (ja) * 2005-03-30 2012-10-31 ビーエーエスエフ ソシエタス・ヨーロピア 硬質表面の防汚処理へのハイドロフォビンの使用方法
CN101228249B (zh) * 2005-04-01 2011-11-30 巴斯福股份公司 含疏水蛋白的钻井液
BRPI0609776A2 (pt) * 2005-04-01 2011-10-18 Basf Ag uso de pelo menos uma hidrofobina, processo para separar pelo menos duas fases lìquidas em uma composição, e, formulação
DE102005025969A1 (de) 2005-06-03 2006-12-28 Basf Ag Verfahren zur Verringerung der Verdunstungsgeschwindigkeit von Flüssigkeiten
WO2006131478A2 (fr) * 2005-06-06 2006-12-14 Basf Aktiengesellschaft Procede d'enduction de surfaces de substrats fibreux
DE102005027139A1 (de) 2005-06-10 2006-12-28 Basf Ag Neue Cystein-verarmte Hydrophobinfusionsproteine, deren Herstellung und Verwendung
DE102005029704A1 (de) * 2005-06-24 2007-01-11 Basf Ag Verwendung von Hydrophobin-Polypeptiden sowie Konjugaten aus Hydrophobin-Polypeptiden mit Wirk-oder Effektstoffen und ihre Herstellung sowie deren Einsatz in der Kosmetik
MX2008001056A (es) * 2005-08-01 2008-03-19 Basf Ag Uso de proteinas no enzimaticas de superficie activa para lavar textiles.
JP2012500241A (ja) * 2008-08-18 2012-01-05 ビーエーエスエフ ソシエタス・ヨーロピア ケラチンの非永久的染色のためのハイドロフォビンの使用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YEAMAN M R ET AL: "Platelet microbicidal proteins and neutrophil and neutrophil defensin disrupt the staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action", JOURNAL OF CLINICAL INVESTIGATION, AMERICAN SOCIETY FOR CLINICAL INVESTIGATION, US, vol. 101, no. 1, 1 January 1998 (1998-01-01), pages 178 - 187, XP002275688, ISSN: 0021-9738, DOI: 10.1172/JCI562 *

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