DE102004012009A1 - Antidandruff compositions, e.g. shampoos, containing synergistic active agent combination of acetylsalicylic acid, zinc pyrithione and piroctone olamine - Google Patents

Abstract

New compositions (I) contain a combination of the antidandruff active agents acetylsalicylic acid (ASA), zinc pyrithione (ZPT) and piroctone olamine (POA), the contents of each of ASA, ZPT and POA each being 0.01-10.0 (preferably 0.05-5.0) wt. % and the combined content of ASA, ZPT and POA being 0.03-20.0 (preferably 0.5-5.0) wt. % (based on (I) in ready-for-use form). An independent claim is included for the use of (I) in the production of preparations for treating dandruff of the hair. ACTIVITY : Antiseborrheic; Fungicide. In plate diffusion tests for activity against Pityrosporum ovale strain CBS 1878, a shampoo formulation containing 1% ASA, 2% ZPT and 0.5% POA gave an inhibition zone of diameter 68 mm, compared with 30.5% for the shampoo without the active agents. MECHANISM OF ACTION : None given.

Description

object The present invention is an agent with cleansing and caring Properties containing a combination of three anti-dandruff active ingredients consisting of the combination Piroctone Olamine, Zinc Pyrithione and acetylsalicylic acid and its use in scaling of the hair-covered skin, especially the scalp.

A Variety of people suffers from dandruff. Already that easy appearance of dandruff on the scalp and hair regarded as a sign of lack of care. Also with a dandruff accompanying itching of the skin is perceived as disturbing. Because itching often causes a scratching reaction, It may be additional come to injuries of the affected skin areas. Associated with it can as further complications infections with pathogenic agents occur.

The usually on hair-covered skin, especially the scalp, Dandruff may occur for a variety of reasons. Usually dandruff is caused by the fact that the constantly regrowing top Horny layer of the epidermis in the form of the smallest scales, the micro scales, is stripped off. With very greasy scalp, microscopic scales can be caused by the from sebaceous glands the hair follicle excreted sebum (sebum) to larger units stick together.

In many cases however, the microbial colonization causes the affected skin a premature one and increased replacement the upper horny layer in the form of scales. Such is for example known that the yeast fungus Pityrosporum ovale (syn. Malassezia furfur) the scalp of scaly carriers in significantly higher densities populated as in persons without scales (SCHRADER, K. In: Grundlagen and recipes of cosmetics, Hüthig (Ed.), 2nd edition, 1989, page 970).

pityrosporum Oval causes the cleavage of the tallow of the skin free fatty acids and lipoperoxides and it comes to irritation of the scalp. Thereby becomes the mitotic activity elevated and there is an increased corneocyte formation, the increased dandruff causes. It is known that by inhibition of Pityrosporum ovale This process is not even set in motion and the dandruff is absent.

The Requirements for a hair cosmetic agent, which dandruff prevent or reduce it, are versatile. on the one Side is supposed to keep the scalp and thus the hair from dandruff be freed. On the other hand, the remedy is not just for the scalp compatible but also the hair should be when using an anti-dandruff agent not damaged and keep its shine and combability.

It There are a number of hair cosmetics that are known for dandruff prevent or reduce the scalp. Such cosmetic Means are available either as shampoos, lotions or hair tonic Available.

in the Case of a microbial origin of dandruff formation was the Application of various special anti-dandruff active ingredients proposed. Such anti-dandruff agents are said to propagate of the microorganisms, in particular Pityrosporum ovale, on the scalp inhibit.

To The known antidandruff active ingredients include in particular the compounds (Bis (1-hydroxy-2- (1H) -pyridinethionato) zinc (INCI name: Zinc Pyrithione, trade name: Zinc Omadine) and 1-hydroxy-4-methyl-6- (2,4,4-trimethylpentyl) -2 (1H) -pyridinone, 2-Aminoethanol salt (INCI name: Piroctone Olamine, trade name: Octopirox®). These compounds are known and commercially available. For example, reference may be made to "International Cosmetic Ingredient Dictionary and Handbook ", Vol. 1-3, Seventh Edition 1997, The Cosmetic, Toiletry, and Fragrance Association, Washington DC. About that In addition, as further anti-dandruff agents are those from the group synthetic or chemical compounds such as acetylsalicylic acid, salicylic acid, sulfur, Tar preparations, Undecensäurederivate and hinokitiol and those from the group of natural products such as Extracts of arnica, birch, burdock root, poplar, stinging nettle or walnut shell known.

A disadvantage, however, is that high concentrations must be used by the said means in order to achieve a scale-reducing or scale-inhibiting effect, with frequent Be glide may cause undesirable effects on the skin and hair.

Furthermore Another disadvantage is that the individual active ingredients no satisfactory effect and not insignificant Can show side effects.

task It was therefore an object of the present invention to provide a means provide, which does not have the aforementioned disadvantages and both an improved scale-reducing and anti-scale effect an existing dandruff as well as a persistent dandruff preventive effect of dandruff unfolds.

According to the invention was the task according to claim 1 solved, after which an agent is provided, containing as active ingredient combination the compounds acetylsalicylic acid (synonym of 2-acetoxybenzoic acid), bis (1-hydroxy-2- (1H) -pyridinethionato) zinc (INCI name: zinc pyrithione) and 1-hydroxy-4-methyl-6- (2,4,4-trimethylpentyl) -2 (1H) -pyridinone, 2-aminoethanol salt (INCI name: Piroctone Olamine).

Surprisingly could namely be found that an agent according to claim 1 and the other embodiments according to the subclaims against the known prior art, the formation of dandruff better prevented or diminished or existing dandruff more effective and more sustainable eliminates or relieves. In addition, as another Advantage can be found that the improved effect even could be achieved with smaller amounts of single active ingredients. This with the combination according to the invention achieved synergism was not expected.

The inventive agent can be beneficial to contraception dandruff or for treatment (elimination or alleviation) an existing dandruff of the scalp or other hair-covered skin surfaces (for example beard region, armpits, intimate area). It is also advantageous that it is known per se on the scalp and on the scalp hair or on the corresponding body parts be applied and after a relatively short exposure time, if necessary again easily by rinsing or washing away can be removed.

Also according to the invention the use of the agent according to the invention for the elimination, reduction and prevention of dandruff on hairy body surfaces, like especially scalp, beard region, underarms, genital area.

In Advantageously, the combination according to the invention at least another synthetic chemical and / or natural Antidandruff added become.

When Synthetic chemical antidandruff agents come for example in consideration: salicylic acid, sulfur, Tar preparations, Undecensäurederivate, Hinokitiol, antibiotics, antimycotics. As natural anti-dandruff agents are Extracts of plant origin, for example burdock root extracts, Poplar extracts, nettle extracts, walnut shell extracts, birch extracts, Willow bark extracts or arnica extracts.

One Another object of the present invention is the use a combination consisting of the active ingredients acetylsalicylic acid, Zinc Pyrithione and Piroctone Olamine for the prevention or reduction of Dandruff or to eliminate and alleviate an already existing dandruff on hairy body surfaces, especially on the Scalp, but also for the preparation of a preparation for the treatment of dandruff the skin, not only the treatment of existing dandruff, but also the preventive, preventing treatment is included.

Based of the known plate diffusion test could with the test organism Pityrosporum ovale be demonstrated that with the combination of the invention acetylsalicylic acid plus Zinc Pyrithione plus Piroctone Olamine become a much larger inhibition center forms as it does with the single active substances or with the combination of two active substances (acetylsalicylic acid and piroctone olamine) the case was. Accordingly, with the combination according to the invention one opposite the individual drugs and combinations of two stronger inhibitory effect of dandruff to achieve. About that it was surprising that comparatively stronger Inhibitory effect could be achieved with drug amounts compared clearly below the amounts of the single active substances or a combination of two lay.

In particular, surprisingly was that the combination of the invention also other combinations with three different anti-dandruff active ingredients with regard to an anti-dandruff action in the sense of a synergistic Superior effect was, as impressive Table 1 shows.

The plate diffusion test carried out with the test organism Pityrosporum ovale is known per se. The following description is intended to illustrate the process by way of example:
In the test organism Pityrosporum ovale syn. Malassezia furfur (strain CBS 6000) was based on a lyophilized culture. Prior to preparation of the vaccine suspension, lyophilized material in Sabouraud broth was pre-cultured with olive oil (Fluka Art. No. 75357, Pityrosporum oval only grows with added oil) (48 hours, 42 ° C). This was followed by two passages on Sabouraud-4% dextrose agar (Merck Art. Nr. 5438), on the surface of which a thin olive oil film was applied with a cotton swab. For this purpose, material from P. ovale was removed from the overgrown broth by means of cotton swabs, applied to the respective culture plates throughout the whole area and incubated for 48 hours at 32.degree. For the preparation of the vaccine suspension, the plate culture was rinsed off with 5.0 ml of Ringer's solution with the addition of 0.1% Tween 80 (Merck Art. No. 822187), taken up with a 5 ml pipette and pipetted into a sterile test tube and well homogenized. The photometer was adjusted to absorbance 1.0 (620 nm). The obtained suspension was used as a seed. 200 ml of said culture medium were inoculated with 0.5 ml of this suspension, mixed well, then poured under sterile conditions, each 20 ml thereof in Petri dishes and allowed to solidify. Two opposing holes (8 mm diameter) were punched out per plate and 0.1 ml each of a shampoo base composition according to Example 1 of each of acetylsalicylic acid (1.0% or 0.5%), zinc pyrithione (2.0% and 1 , 0%) and piroctone olamine (0.5%) or a combination of acetylsalicylic acid plus octopirox (1.0% and 0.5%, respectively) and a combination of acetylsalicylic acid (1.0%) plus zinc pyrithione ( 1.0%) plus piroctone olamine (0.5%). The plates thus charged were incubated at 32 ° C for 48 hours with the lid facing upwards and then measured the diameter of the Hemmhöfe.

The the Hemmhofdurchmesser obtained by the above method (Hole diameter 8 mm) after the plate diffusion test with various strains of Pityrosporum ovale (Malassezia furfur) CBS6000 and DSM6170, that the combination according to the invention far superior to the combinations of two and the individual substances was what characterized by the largest Hemmhofdurchmesser with the combination according to the invention showed.

The Table 1 below shows that after that described above Procedure obtained Hemmhofdurchmesser with different combinations from three single active substances, which correspond to the different strains of Pityrosporum ovale (Malassezia furfur) CBS1878, CBS6000, DSM6170, IHEM3965, IHM3966.

Table 1: Diameter of Hemmhofzonen in mm, quantity in percent by weight based on the total weight of the ready-to-use composition

In quite impressively, Table 1 shows the superiority of the combination according to the invention from acetylsalicylic acid plus zinc pyrithione plus octopirox (= piroctone olamine) over the other combinations.

Out The obtained averages show clearly that the combination Acetlysalicylsäure + Zinc Pyrithione + Octopyrox (= Piroctone Olamine) with the value 51.2 superior to all other combinations of three active ingredients is. Even at lower concentrations of acetylsalicylic acid (0.5 % By weight), the values remained constant.

The Combination without acetylsalicylic acid with 2.0 wt .-% zinc pyrithione and 0.5 wt .-% octopyrox yielded significantly lower Hemmhofdurchmesser (not shown), so that the synergistic effect of acetylsalicylic acid in the combination according to the invention could be unambiguously substantiated by this counter-experiment.

The hair cosmetic according to the invention Means can in all customary Dosage forms available. For example as shampoos (antidandruff shampoos), shower rooms (e.g., shower gels), cures (anti-dandruff treatments), rinses (antidandruff rinses), hair lotions (Antidandruff hair tonics), hydrous hair sprays, foams, Gels, fortifiers, deodorants (e.g., deodorant sticks), shaving lotions, ointments or creams.

preferred Dosage form is a shampoo, most preferably a formulation based on an alkyl ether sulfate or an alkyl ether sulfate-containing Surfactant mixture. Preferred surfactants are conventional anionic, amphoteric, zwitterionic and / or nonionic surfactants into consideration.

The The relevant forms of preparation may in all cases be comparable usual cosmetic products containers bottled and provided.

The inventive combination the antidandruff active ingredients can be easily incorporated by known methods every usual Basic composition for cosmetic or therapeutic products are incorporated, wherein an amount of active ingredient between 0.01 and 10.0 weight percent (wt .-%) per active ingredient (acetylsalicylic acid, Zinc Pyrithione, Piroctone Olamine) based on the total weight the ready-to-use composition comes into consideration, preferably in an amount of 0.05 to 5.0 wt .-% per active ingredient. The amount the combination of all three active ingredients in the ready-to-use composition may therefore be in a range between 0.03 and 20.0 wt .-%, preferably between 0.1 and 10.0 wt .-%, in particular between 0.5 and 5.0 % By weight, based in each case on the total weight of the ready-to-use Composition.

A such composition may be at least one other synthetic chemical antidandruff active ingredients and / or those based on natural substances contain. For example, salicylic acid, sulfur, tar preparations, Undecensäurederivate, Hinokitiol, extracts of arnica, birch, burdock root, poplar, stinging nettle or walnut shell. The amounts of these agents can in the range between 0.001 and 10.0 wt .-%, in particular between 0.01 and 5.0% by weight, especially between 0.05 and 2.0% by weight per active ingredient based on the ready-to-use composition.

The inventive agent can all the usual and known additives, excipients and carriers. For example Thickeners such as bentonite, fatty acids, starch, polyacrylic acid and their derivatives, cellulose derivatives and alginates; Wetting agent or Emulsifiers, anionic, cationic, amphoteric, zwitterionic or nonionic surfactant Substances (surfactants), for example fatty alcohol sulfates, fatty alcohol ether sulfates, Alkyl sulfonates, alkyl benzene sulfates, quaternary ammonium salts, alkyl betaines, ethoxylated alkylphenols, fatty acid alkanolamides or ethoxylated fatty acid esters; Silicone surfactants or silicone oils (for example Dimethicones), alcohols such as ethanol, Propanol, isopropanol or glycerin; Solubilizers, stabilizers, Fragrances or perfumes, Perfume oils, dyes (For example, natural dyes or synthetic, substantive Dyes) but also staining dyes (for example, fluorescein sodium salt), hair conditioning and hair-care ingredients or care substances such as cationic polymers, Lanolin derivatives, cholesterol, pantothenic acid and betaine, Konvervierungsmittel, inorganic or organic acids (for example, phosphoric acid, Acetic acid, Lactic acid) Bases, salts (for example sodium chloride), buffers (for example Sodium citrate or sodium phosphate), bodying agents (cellulose derivatives), Sunscreens or UV filters, natural, semi-synthetic or fully synthetic Polymers (such as chitosan, FMOC-chitosan, PVP).

To the exemplified additives or excipients and carriers, in the agent of the invention can be included counting for example, preservatives such as para-hydroxybenzoic acid esters in an amount of 0.05 to 2.0% by weight), benzoic acid and formic acid, fungicidal and bacteriocidal agents (for example, 2,4,4-trichloro-2-hydroxyphenyl ether or methylchloroisothiazolinone), plant extracts (e.g. Nettle extract or chamomile extract in an amount of 0.1 to 2.0% by weight), light stabilizers (for example, p-methoxycinnamic acid isoamyl ester in an amount of 0.01 to 2.0 weight percent), thickener (For example, cellulose and esters thereof in an amount of 0.5 to 3.0% by weight), hair-care ingredients (for example apple wax, Ilex resin, lanolin, beeswax, panthenol, fatty alcohols, fatty acids, triglycerides, Ceramides, betaine, carnitine esters, amino acids, peptides, proteins, vitamins, and mixtures thereof in an amount of 0.1 to 2.0% by weight). Vitamins such as vitamin C, vitamin B (biotin), Vitamin E (tocopherols) each in an amount of 0.001 to 2.0 Weight percent into consideration. As proteins, for example, keratin in an amount of 0.1 to 4.0 percent by weight. As amino acids For example, cysteine or alanine in an amount of 0.01 called to 0.5 weight percent. As emulsifiers, in particular non-ionic emulsifiers, for example Plantacare or alkyloligoglucoside from Henkel, Dusseldorf, Germany, used in an amount of 0.1 to 2.0 weight percent become. As a solubilizer For example, Cremophore RH 410 or glycerol-polyethylene glycol oxystearate is used from BASF, Ludwigshafen, Germany, in an amount of 0.1 to 2.0 weight percent in question.

When silicone oils can the known products are used, for example Dimethicone (e.g., Dow Corning 200 fluids), phenyltrimethicones (e.g., Abil AV types Goldschmidt), cyclomethicones (e.g., Dow Corning 244 Fluid), Dimethiconol (e.g., Dow Corning 1401), alkyl dimethicone (e.g., Dow Corning 2502 and 2503) or amino-functional silicones (e.g., Dow Corning 939 or 8220). The silicone oils can be used in concentrations of From 0.02 to 5% by weight, based on the total weight of the finished product, be used.

The anionic, cationic, amphoteric, zwitterionic or nonionic Surfactants can used singly or in a mixture.

When anionic surfactants are alkali, alkaline earth, ammonium or Alkanolamine salts of alkanesulfonates, alkyl sulfonates and alkyl ether sulfates, which contain in particular 12 to 18 carbon atoms in the alkyl radical can, in particular the sodium or triethanolamine salts of lauryl or Tetradecyl.

Concerning cationic surfactants are fatty amines, quaternary ammonium compounds, for example Genamin ^® CTAC or cetyltrimethylammonium chloride (Hoechst, Germany), quaternary compounds of pyridine, morpholine or imidazoline of the contemplated.

When nonionic surfactant Substances can ethoxylated fatty alcohols having 12 to 18 carbon atoms and with up to 40 moles of ethylene oxide per mole of fatty alcohol can be used such as ethoxylated lauryl, tetradecyl, cetyl, oleyl or stearyl alcohol, alone or in admixture, as well as fatty alcohols of ethoxylated lanolin or ethoxylated lanolin. But also fatty amine, fatty acid and ethoxylated sorbitan fatty acid esters are suitable as surfactant or surfactant mixture.

Under the amphoteric, surface-active Substances are, for example, the N-alkylbetaines, the N-alkylaminobetaines, the N-alkylsulfobetaines, the N-alkylaminopropionates, the alkyldimethylammonium acetates or the fatty acid alkylamidobetaines are suitable Wash-active raw materials as further components of the hair cosmetic according to the invention To call by means.

Cationic polymers are also known in the art and are commercially available. One or more cationic polymers can be added. Suitable for this purpose are all cosmetically acceptable, cationically charged polymers, for example Luviquat ^® FC 905 (copolymer of vinylimidazolium methochloride / vinylpyrrolidone and Polyquaternium-16) available from BASF, Ludwigshafen, Germany, or Gafquat ^® 755 N (copolymer of vinylpyrrolidone / dimethylaminoethyl methacrylate or Polyquaternium 11) from ISP, New Jersey, USA, or Abil Quat 3272 (diquameric polydimethylsiloxane or quaternium-80) from Th. Goldschmidt AG, Essen, Germany, or Ucare Polymer JR400 (Polyquaternium-10) from Amerchol, New Jersey, USA, or Cosmedia Guar C 261 (hydroxypropyl guar hydroxypropyltrimonium chloride) from Henkel, Dusseldorf, Germany, or Jaguar C13S (guar hydroxypropyltrimonium chloride) from Rhône Poulenc, France, or Merquat 550 (Polyquaternium 7) from Chemviron SA, or Lamequat L (lauryldimonium hydroxypropyl hydrolyzed collagen ) of the company Grünau / Henkel. The cationic polymers can be used in concentrations of 0.01 to 3 percent by weight.

Except the The abovementioned constituents can still hair care agents according to the invention contain other components that are common in hair products be applied. These include Bodying agents and thickeners such as agar-agar, guar-gum, alginates and xanthan gum or esters of ethoxylated polyols and fatty acids such as Polyglyceryl (2) polyoxyethylene (4) stearate, oils and waxes, e.g. triglycerides vegetable or animal origin, spermaceti, beeswax, montan wax, Paraffin oils, Vaseline, Wool wax, fruit and other vegetable waxes.

Regarding the usual cosmetic additives can also referred to the publications and monographs known in the art For example, regarding shampoo compositions DORNSCH, Andreas, The cosmetic preparations, Publisher chem. Industrie, H. Ziolkowsky KG, Augsburg, edition, volume 2, pages 212-230, 1,992th

The hair cosmetic according to the invention Agent may have a pH in the range of between 1.0 and 9.0, preferably in the range between 4.0 and 7.0, especially in the range between 4.5 and 5.6. If desired, can for the setting of a physiologically acceptable pH is a suitable Acid used become. Therefor is the addition of citric acid, tartaric acid, lactic acid, adipic acid, glyoxylic acid, gluconic acid, malic acid or Phosphoric acid.

It It has been found that the desired anti-dandruff effect can be achieved in an advantageous manner, when the inventive agent for example, in the form of a shampoo for shampooing with the skin surface of the head is brought into contact. When applied hair lotions, cures or douching be the appropriate remedy daily or at least once weekly over one Period of days, weeks or months or continuously applied. The duration and frequency The application may vary with the type, education and strength of the expression of the Scalp scales are related.

The The following examples are intended to describe the subject matter of the invention in more detail. The specified numerical values are percentages by weight based on 100% Pure substance.

Example 1: Antidandruff shampoo

For the composition according to the invention A can be opposite Comparative compositions B to F a significantly better anti-dandruff action be recognized.

The Preparation of the above recipe can after itself take place known methods. The raw materials are well known and are commercially available.

Claims (7)

Agent containing as a combination the anti-dandruff agents a) acetylsalicylic acid in an amount of 0.01 to 10.0 weight percent, preferably 0.05 up to 5.0 weight percent, b) Zinc Pyrithione in a crowd from 0.01 to 10.0 weight percent, preferably 0.05 to 5.0 weight percent, c) Piroctone olamine in an amount of 0.01 to 10.0 weight percent, preferably 0.05 to 5.0 percent by weight, each related on the total weight of the ready-to-use composition, being the amount of the combination of all three active ingredients a), b) and c) in the ready-to-use composition in the range between 0.03 and 20.0 weight percent, preferably between 0.1 and 10.0 weight percent, more preferably between 0.5 and 5.0 weight percent, respectively based on the total weight of the ready-to-use composition. Means according to claim 1, characterized in that it in addition at least one more synthetic chemical or natural Antidandruff agent in an amount of 0.001 to 10.0 weight percent, in particular between 0.01 and 5.0 weight percent, most preferably between 0.05 and 2.0% by weight. Means according to claim 2, characterized in that the other natural or synthetic chemical or natural antidandruff agent is selected from salicylic acid, Sulfur, tar preparations, Undecensäurederivate, Hinokitiol, burdock root extracts, poplar extracts, stinging nettle extracts, Walnußschalenextrakten, Birch extracts, willow bark extracts or arnica extracts. Means according to claims 1 to 3, characterized in that it is used as a shampoo, shower bath, Shower gel, gel, cure, conditioner, Hair lotions, Hair spray, foam, stiffener, deodorant, aftershave is present. Use of a combination consisting of the active ingredients a) acetylsalicylic acid in an amount of 0.01 to 10.0 percent by weight, preferably 0.05 to 5.0 percent by weight, b) zinc pyrithione in an amount of 0.01 to 10.0 percent by weight, preferably 0.05 to 5.0 percent by weight, c) Piroctone olamine in an amount of 0.01 to 10.0 weight percent, preferably 0.05 to 5.0 weight percent, each based on the total weight of the ready-to-use composition, wherein the amount of the combination of all three active ingredients a), b) and c) in the ready-to-use composition is in the range between 0.03 and 20.0 percent by weight, preferably between 0.1 and 10.0 percent by weight, more preferably between 0.5 and 5.0 percent by weight, based in each case on the total weight of the ready-to-use Composition, for the prevention or reduction of dandruff or for the removal and alleviation of existing dandruff on hairy body surfaces. Use according to claim 5, characterized that the hairy body surfaces the scalp, the beard region, the armpits or the genital area Using a combination of a) acetylsalicylic acid in one Amount of 0.01 to 10.0 weight percent, preferably 0.05 to 5.0 Percent by weight, b) Zinc pyrithione in an amount of 0.01 to 10.0 weight percent, preferably 0.05 to 5.0 weight percent, c) Piroctone olamine in an amount of 0.01 to 10.0 weight percent, preferably 0.05 to 5.0 percent by weight, each related on the total weight of the ready-to-use composition, being the amount of the combination of all three active ingredients a), b) and c) in the ready-to-use composition in the range between 0.03 and 20.0 weight percent, preferably between 0.1 and 10.0 weight percent, more preferably between 0.5 and 5.0 weight percent, respectively based on the total weight of the ready-to-use composition, for preparing a preparation for the Treatment of dandruff of the skin.