WO2006122685A1

WO2006122685A1 - Compositions for the treatment of psoriasis

Info

Publication number: WO2006122685A1
Application number: PCT/EP2006/004373
Authority: WO
Inventors: Nicola Nardiello
Original assignee: Greenleaf Srl
Priority date: 2005-05-17
Filing date: 2006-05-10
Publication date: 2006-11-23
Also published as: ITMI20050891A1; EP1881833A1

Abstract

What is claimed are compositions for the treatment of psoriasis, eczema and inflammatory conditions of the skin comprising as an active ingredient a therapeutic effective amount of thiamine or its cosmetically and/or toxicologically acceptable salts.

Description

Compositions for the treatment of Psoriasis

Object of the invention

The present invention concerns compositions comprising thiamine for the treatment of psoriasis, eczemas of different nature and all kind of inflammatory diseases of the skin.

State of the art

Psoriasis is a highly diffuse, chronic and recidive dermatological disease effecting between 2 and 4 % of the population and is characterized by dryness of the skin; pimples and plaques mostly localized in the face, the limbs and the back, but can sometimes also affect the entire body.

Some effects can be relatively light and limited while others can show a very serious character also weakening the patient (psoriasis esfoliativά). Until today no therapies exist providing a guarantee for an effective success over the time. Usually corticosteroids for topical application, emollients, lubricants and peelings are used. In more serious cases oral administration of methotrexate or PUVA is suggested, which stands for a combination of photo-sensitizing agents (so-called "psoralens") and UV radiation, optionally in combination with the oral administration of retinoid compounds, like isotretinoin or etretinate (see e.g. US 4,269,851). Also proposed is the use of immunosuppressant drugs like cyclosporin and tacrolimus. US 2005272691 A (Devlin et al.) proposes for the treatment of dermatological conditions, such as psoriasis, dermatitis, and dandruff the administration of a vitamin supplement composition comprising folic acid, vitamin B 12 and/or vitamin B6. The vitamin supplement composition may also be essentially free of antioxidants.

Since the effects achievable by the treatments according to the state of the art are not fully satisfying there is still a need for a more effective, reliable and simple treatment substantially lacking risks. Description of the invention

The present invention claims compositions for the treatment of psoriasis, eczema and inflam- matory conditions of the skin comprising as an active ingredient a therapeutic effective amount of thiamine or its toxicologically and/or cosmetically acceptable salts.

It has been found that thiamine (Vitamin Bl) administered in high doses either topical or sys- temically (oral or by injection) shows to be particular effective and has led to surprising thera- peutic results in mild cases as well as in serious cases where great parts of the skin were affected. Therefore, the present invention refers to cosmetically and pharmaceutically treatment both.

Thiamine (Vitamin BH

Thiamine is a synonym for the well known Vitamin Bl. Usually, thiamine is present in the form of its chloride (3-[4-Amino-2-methyl-5-pyrimidinyl)-methyl]-5-(2-hydroxyethyl)-4-methylthia- zoniumchloride),

which is both cosmetically acceptable and non-toxic, so that in can be used in both topical and oral administration. For high doses the topical application of formulations comprising at least 10 % b.w. of thiamine, preferably of at least 30 % b.w. and more preferably of at least 40 % b.w. or its cosmetically acceptable (and non-toxic) salts, like for example its chloride is suggested. Formulations comprising about 50 to about 60 % b.w. of thiamine or its salts have been found rather useful for therapeutic applications, especially in the course of some prelimi- nary clinical studies. In a preferred embodiment the cosmetic compositions of the present invention comprise

(a) thiamine or its cosmetically acceptable salts,

(b) anti-inflammatory ingredients and/or

(c) carriers and/or excipients;

and more particularly

(a) 10 to 60, particularly 20 to 40 % b.w. thiamine or its cosmetically acceptable salts,

(b) 0 to 20, particularly 1 to 15 % b.w. anti-inflammatory ingredients and/or

(c) 0 to 20, particularly 1 to 15 % b.w. carriers and/or excipients

with the condition that the amounts add optionally together with water and additional cosmetic ingredients to 100 % b.w. Said anti-inflammatory ingredients may be selected from the group consisting of salicylic acid, glyzyrrhetinic acid, conjugated linoleic acid, benzoyl peroxide, chi- tosan, Vitamin B6, and plant actives obtainable by extracts of the following plants: Aesculus hippocastanum (Horse chestnut), Argania spinosa, Babtista tinctoria (wild indigo), Cantella asiatica, Camelilla sinensis (green tea), Chamonella recutita (Camilla), Ginkgo biloba (Ginkgo), Oleo europea (Olive), Litschi chinensis (Litchi), Melissa officinalis (Melissa), Panax ginseng (Ginseng), Passiflora incarnata (Passion flower, Prunus dulcis (Sweet Almond), Pterocarpus marsupium, Ruscus aculeatus, Trifolium pratense (Red Clover), Uva ursi, Vaccinium myrtillus (Blueberry), Vigna acontifolia, and Vitis vinifera.

Industrial application

A second embodiment of the present invention is directed to the use of thiamine or its nontoxic salts for the preparation of a medicament for the treatment of psoriasis, eczema and inflammatory diseases of the skin. The treatment of the diseases can be conducted either by topical or oral administration. Preferably, thiamine or its non-toxic salt is present in an amount of at least 10 to at least 60 % b.w. in the medicament.

The way of topical treatment is preferred even although oral administration is also useful and sometimes even more favourable. In these cases, the doses may vary between 2 and 6 g to the day, eventually subdivided in more applications. In case of administration by injection, for example intramuscular, the doses may vary from 2 to 6 g, eventually subdivided in more parts.

The administration of a cream formulation comprising 50 % b.w. thiamine (as its chloride) two times a day over a period of 4 to 8 weeks to various patients suffering from psoriasis led to significant improvements, which was monitored by taking photos over the full period. The improvements could be seen only after two weeks from the beginning of the treatment. For the topical treatments suitable formulations as for example gels, lotions, creams, sprays, emulsions and the like. In a preferred embodiment of the present inventions the compositions are encap- sulated, e.g. in a gelatin shell or micro-encapsulated. "Microcapsules" are understood to be spherical aggregates with a diameter of about 0.1 to about 5 mm which contain at least one solid or liquid core surrounded by at least one continuous membrane. More precisely, they are finely dispersed liquid or solid phases coated with film-forming polymers, in the production of which the polymers are deposited onto the material to be encapsulated after emulsification and coacervation or interfacial polymerization. In another process, liquid active principles are absorbed in a matrix ("microsponge") and, as microparticles, may be additionally coated with film-forming polymers. The microscopically small capsules, also known as nanocapsules, can be dried in the same way as powders. Besides single-core microcapsules, there are also multiple-core aggregates, also known as microspheres, which contain two or more cores distributed in the continuous membrane material. In addition, single-core or multiple-core microcapsules may be surrounded by an additional second, third etc. membrane. The membrane may consist of natural, semisynthetic or synthetic materials. Natural membrane materials are, for example, gum arabic, agar agar, agarose, maltodextrins, alginic acid and salts thereof, for example sodium or calcium alginate, fats and fatty acids, cetyl alcohol, collagen, chitosan, lecithins, gela- tin, albumin, shellac, polysaccharides, such as starch or dextran, polypeptides, protein hydro- lyzates, sucrose and waxes. Semisynthetic membrane materials are inter alia chemically modified celluloses, more particularly cellulose esters and ethers, for example cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and carboxymethyl cellulose, and starch derivatives, more particularly starch ethers and esters. Synthetic mem- brane materials are, for example, polymers, such as polyacrylates, polyamides, polyvinyl alcohol or polyvinyl pyrrolidone.

Examples of known microcapsules are the following commercial products (the membrane material is shown in brackets) Hallcrest Microcapsules (gelatin, gum arabic), Coletica Thalas- pheres (maritime collagen), Lipotec Millicapseln (alginic acid, agar agar), Induchem Unispheres (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Unicetin C30 (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Kobo Glycospheres (modified starch, fatty acid esters, phospholipids), Softspheres (modified agar agar) and Kuhs Probiol Nanospheres (phospholipids).

Cosmetic and pharmaceutical compositions

The preparations according to the invention may contain surfactants, oil bodies, emulsifiers, superfatting agents, pearlising waxes, consistency factors, polymers, silicone compounds, waxes, stabilizers, primary and secondary sun protection agents, biogenic agents, film formers, hydrotropes, preservatives, solubilizers, perfume oils, dyes and the like as additional auxiliaries and additives.

Surfactants

Preferred auxiliaries and additives are anionic and/or amphoteric or zwitterionic surfactants. Typical examples of anionic surfactants are soaps, alkyl benzenesulfonates, alkanesulfonates, olefin sulfonates, alkylether sulfonates, glycerol ether sulfonates, methyl ester sulfonates, sulfo- fatty acids, alkyl sulfates, fatty alcohol ether sulfates, glycerol ether sulfates, fatty acid ether sulfates, hydroxy mixed ether sulfates, monoglyceride (ether) sulfates, fatty acid amide (ether) sulfates, mono- and dialkyl sulfosuccinates, mono- and dialkyl sulfosuccinamates, sulfotrigly- cerides, amide soaps, ether carboxylic acids and salts thereof, fatty acid isethionates, fatty acid sarcosinates, fatty acid taurides, N-acylamino acids such as, for example, acyl lactylates, acyl tartrates, acyl glutamates and acyl aspartates, alkyl oligoglucoside sulfates, protein fatty acid condensates (particularly wheat-based vegetable products) and alkyl (ether) phosphates. If the anionic surfactants contain polyglycol ether chains, they may have a conventional homolog distribution although they preferably have a narrow-range homolog distribution. Typical examples of amphoteric or zwitterionic surfactants are alkylbetaines, alkylamidobetaines, amino- propionates, aminoglycinates, imidazolinium betaines and sulfobetaines. The surfactants men- tioned are all known compounds. Information on their structure and production can be found in relevant synoptic works, cf. for example J. Falbe (ed.), "Surfactants in Consumer Products", Springer Verlag, Berlin, 1987, pages 54 to 124 or J. Falbe (ed.), "Katalysatoren, Tenside und Mineralδladditive (Catalysts, Surfactants and Mineral Oil Additives)", Thieme Verlag, Stuttgart, 1978, pages 123-217. The percentage content of surfactants in the preparations may be from 0.1 to 10% by weight and is preferably from 0.5 to 5% by weight, based on the preparation. Oil bodies

Suitable oil bodies, which form constituents of W/O or OAV emulsions, are, for example, Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of linear C₆-C₂₂-fatty acids with linear or branched C₆-C₂₂-fatty alcohols or esters of branched C₆-C ₁₃-carboxylic acids with linear or branched C₆-C ^-fatty alcohols, such as, for example, myristyl myristate, myristyl palmitate, myristyl stearate, myristyl isostearate, myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, stearyl palmitate, stearyl stearate, stearyl isostearate, stearyl oleate, stearyl behenate, stearyl erucate, isostearyl myristate, isostearyl palmitate, isostearyl stearate, isostearyl isostearate, isostearyl oleate, isostearyl behenate, isostearyl oleate, oleyl myristate, oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl stearate, behenyl isostearate, behenyl oleate, behenyl behenate, behenyl erucate, erucyl myristate, erucyl palmitate, erucyl stearate, erucyl isostearate, erucyl oleate, erucyl behenate and erucyl erucate. Also suitable are esters of linear Q-C^-fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of CiS-C₃₈- alkylhydroxy carboxylic acids with linear or branched C₆-C ₂₂-fatty alcohols, in particular Dioctyl Malate, esters of linear and/or branched fatty acids with polyhydric alcohols (such as, for example, propylene glycol, dimerdiol or trimertriol) and/or Guerbet alcohols, triglycerides based on C₆ -Cio-fatty acids, liquid mono- /di-/triglyceride mixtures based on C₆-Ci₈-fatty acids, esters of C₆- C₂2-fatty alcohols and/or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C₂- Ci₂- dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon atoms or polyols having 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary al- cohols, substituted cyclohexanes, linear and branched C₆-C₂₂-fatty alcohol carbonates, such as, for example, Dicaprylyl Carbonate (Cetiol® CC), Guerbet carbonates, based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of benzoic acid with linear and/or branched C₆-C₂₂-alcohols (e.g. Finsolv® TN), linear or branched, symmetrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, such as, for example, dicaprylyl ether (Cetiol® OE), ring-opening products of epoxidized fatty acid esters with polyols, silicone oils (cyclomethicones, silicone methicone grades, etc.) and/or aliphatic or naphthenic hydrocarbons, such as, for example, squalane, squalene or dialkylcyclohexanes. Emulsifiers

Other surfactants may also be added to the preparations as emulsifiers, including for example:

• products of the addition of 2 to 30 mol ethylene oxide and/or 0 to 5 mol propylene oxide onto linear C_8-22 fatty alcohols, onto Ci_2-22 fatty acids and onto alkyl phenols containing 8 to 15 carbon atoms in the alkyl group;

• C₁₂/i₈ fatty acid monoesters and diesters of addition products of 1 to 30 mol ethylene oxide onto glycerol; • glycerol mono- and diesters and sorbitan mono- and diesters of saturated and unsaturated fatty acids containing 6 to 22 carbon atoms and ethylene oxide addition products thereof;

• addition products of 15 to 60 mol ethylene oxide onto castor oil and/or hydrogenated castor oil; • polyol esters and, in particular, polyglycerol esters such as, for example, polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate or polyglycerol dimerate isostearate. Mixtures of compounds from several of these classes are also suitable;

• addition products of 2 to 15 mol ethylene oxide onto castor oil and/or hydrogenated castor oil; • partial esters based on linear, branched, unsaturated or saturated Cβrxi fatty acids, rici- noleic acid and 12-hydroxystearic acid and glycerol, polyglycerol, pentaerythritol, - dipentaerythritol, sugar alcohols (for example sorbitol), alkyl glucosides (for example methyl glucoside, butyl glucoside, lauryl glucoside) and polyglucosides (for example cellulose); • mono-, di and trialkyl phosphates and mono-, di- and/or tri-PEG-alkyl phosphates and salts thereof;

• wool wax alcohols;

• polysiloxane/polyalkyl polyether copolymers and corresponding derivatives;

• mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and/or mixed esters of C_6-22 fatty acids, methyl glucose and polyols, preferably glycerol or polyglycerol,

• polyalkylene glycols and

• glycerol carbonate.

The addition products of ethylene oxide and/or propylene oxide onto fatty alcohols, fatty acids, alkylphenols, glycerol mono- and diesters and sorbitan mono- and diesters of fatty acids or onto castor oil are known commercially available products. They are homologue mixtures of which the average degree of alkoxylation corresponds to the ratio between the quantities of ethylene oxide and/or propylene oxide and substrate with which the addition reaction is carried out. C₁₂/₁₈ fatty acid monoesters and diesters of addition products of ethylene oxide onto glycerol are known as lipid layer enhancers for cosmetic formulations.

Typical anionic emulsifiers are aliphatic C_12-22 fatty acids, such as palmitic acid, stearic acid or behenic acid for example, and C_12-22 dicarboxylic acids, such as azelaic acid or sebacic acid for example.

Superfatting agents

Superfatting agents may be selected from such substances as, for example, lanolin and lecithin and also polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides, the fatty acid alkanolamides also serving as foam stabilizers.

Consistency factors

The consistency factors mainly used are fatty alcohols or hydroxyfatty alcohols containing 12 to 22 and preferably 16 to 18 carbon atoms and also partial glycerides, fatty acids or hydroxyfatty acids. A combination of these substances with alkyl oligoglucosides and/or fatty acid N- methyl glucamides of the same chain length and/or polyglycerol poly-12-hydroxystearates is preferably used.

Thickening agents

Suitable thickeners are polymeric thickeners, such as Aerosil® types (hydrophilic silicas), poly- saccharides, more especially xanthan gum, guar-guar, agar-agar, alginates and tyloses, car- boxymethyl cellulose and hydroxyethyl cellulose, also relatively high molecular weight polyethylene glycol monoesters and diesters of fatty acids, polyacrylates (for example Carbopols® [Goodrich] or Synthalens® [Sigma]), polyacrylamides, polyvinyl alcohol and polyvinyl pyrroli- done, surfactants such as, for example, ethoxylated fatty acid glycerides, esters of fatty acids with polyols, for example pentaerythritol or trimethylol propane, narrow-range fatty alcohol ethoxylates and electrolytes, such as sodium chloride and ammonium chloride. Polymers

Suitable cationic polymers are, for example, cationic cellulose derivatives such as, for example, the quaternized hydroxyethyl cellulose obtainable from Amerchol under the name of Polymer JR 400®, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinyl pyrrolidone/vinyl imidazole polymers such as, for example, Luviquat® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides such as, for example, Lauryldimonium Hydroxypropyl Hydrolyzed Collagen (Lamequat® L, Griinau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers such as, for exam- pie, amodimethicone, copolymers of adipic acid and dimethylaminohydroxypropyl diethylene- triamine (Cartaretine^®, Sandoz), copolymers of acrylic acid with dimethyl diallyl ammonium chloride (Merquat^® 550, Chemviron), polyaminopolyamides and crosslinked water-soluble polymers thereof, cationic chitin derivatives such as, for example, quaternized chitosan, optionally in microcrystalline distribution, condensation products of dihaloalkyls, for example dibro- mobutane, with bis-dialkylamines, for example bis-dimethylamino- 1,3 -propane, cationic guar gum such as, for example, Jaguar^®CBS, Jaguar^®C-17, Jaguar^®C-16 of Celanese, quaternized ammonium salt polymers such as, for example, Mirapol^® A- 15, Mirapol^® AD-I, Mirapol^® AZ-I ofMiranol.

Suitable anionic, zwitterionic, amphoteric and nonionic polymers are, for example, vinyl ace- tate/crotonic acid copolymers, vinyl pyrrolidone/vinyl acrylate copolymers, vinyl acetate/butyl maleate/isobornyl acrylate copolymers, methyl vinylether/maleic anhydride copolymers and esters thereof, uncrosslinked and polyol-crosslinked polyacrylic acids, acrylamidopropyl trimethylammonium chloride/acrylate copolymers, octylacrylamide/methyl methacrylate/tert.- butylaminoethyl methacrylate/2-hydroxypropyl methacrylate copolymers, polyvinyl pyrroli- done, vinyl pyrrolidone/vinyl acetate copolymers, vinyl pyrrolidone/dimethylaminoethyl methacrylate/vinyl caprolactam terpolymers and optionally derivatized cellulose ethers and silicones.

Silicones

Suitable silicone compounds are, for example, dimethyl polysiloxanes, methylphenyl polysilox- anes, cyclic silicones and amino-, fatty acid-, alcohol-, polyether-, epoxy-, fluorine-, glycoside- and/or alkyl-modified silicone compounds which may be both liquid and resin-like at room temperature. Other suitable silicone compounds are simethicones which are mixtures of dime- thicones with an average chain length of 200 to 300 dimethylsiloxane units and hydrogenated silicates. Waxes

Besides natural oils used, waxes may also be present in the preparations, more especially natural waxes such as, for example, candelilla wax, carnauba wax, Japan wax, espartograss wax, cork wax, guaruma wax, rice oil wax, sugar cane wax, ouricury wax, montan wax, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial fat, ceresine, ozocerite (earth wax), petrolatum, paraffin waxes and microwaxes; chemically modified waxes (hard waxes) such as, for example, montan ester waxes, sasol waxes, hydrogenated jojoba waxes and synthetic waxes such as, for example, polyalkylene waxes and polyethylene glycol waxes.

Stabilizers

Metal salts of fatty acids such as, for example, magnesium, aluminium and/or zinc stearate or ricinoleate may be used as stabilizers.

Primary sun protection factors

Primary sun protection factors in the context of the invention are, for example, organic substances (light filters) which are liquid or crystalline at room temperature and which are capable of absorbing ultraviolet radiation and of releasing the energy absorbed in the form of longer- wave radiation, for example heat. UV-B filters can be oil-soluble or water-soluble. The following are examples of oil-soluble substances:

• 3-benzylidene camphor or 3-benzylidene norcamphor and derivatives thereof, for example 3 -(4-methylbenzylidene)-camphor;

• 4-aminobenzoic acid derivatives, preferably 4-(dimethylamino)benzoic acid-2-ethyl- hexyl ester, 4-(dimethylamino)-benzoic acid-2-octyl ester and 4-(dimethylamino)ben- zoic acid amyl ester;

• esters of cinnamic acid, preferably 4-methoxycinnamic acid-2-ethylhexyl ester, 4- methoxycinnamic acid propyl ester, 4-methoxycinnamic acid isoamyl ester, 2-cyano- 3,3-phenylcinnamic acid-2-ethylhexyl ester (Octocrylene);

• esters of salicylic acid, preferably salicylic acid-2-ethylhexyl ester, salicylic acid-4- isopropylbenzyl ester, salicylic acid homomenthyl ester;

• derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2- hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;

• esters of benzalmalonic acid, preferably 4-methoxybenzalmalonic acid di-2-ethylhexyl ester;

• triazine derivatives such as, for example, 2,4,6-trianilino-(p-carbo-2'-ethyl-r-hexyloxy)- 1,3,5-triazine and Octyl Triazone or Dioctyl Butamido Triazone (Uvasorb^® HEB);

• propane- 1, 3 -diones such as, for example, l-(4-tert.butylphenyl)-3-(4'-methoxyphenyl)- propane-l,3-dione;

• ketotricyclo(5.2.1.0)decane derivatives.

Suitable water-soluble substances are

• 2-phenylbenzimidazole-5-sulfonic acid and alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium and glucammonium salts thereof;

• sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzo- phenone-5-sulfonic acid and salts thereof;

• sulfonic acid derivatives of 3-benzylidene camphor such as, for example, 4-(2-oxo-3- bornylidenemethyl)-benzene sulfonic acid and 2-methyl-5-(2-oxo-3-bornylidene)- sulfonic acid and salts thereof.

Typical UV-A filters are, in particular, derivatives of benzoyl methane such as, for example, 1- (4'-tert.butylphenyl)-3-(4'-methoxyphenyl)-propane-l,3-dione, 4-tert.butyl-4'-methoxydiben- zoyl methane (Parsol^® 1789) or l-phenyl-3-(4'-isopropylphenyl)-propane-l,3-dione and the enamine compounds (BASF). The UV-A and UV-B filters may of course also be used in the form of mixtures. Particularly favourable combinations consist of the derivatives of benzoyl methane, for example 4-tert.butyl-4'-methoxydibenzoyl methane (Parsol^® 1789) and 2-cyano- 3,3-phenylcinnamic acid-2-ethylhexyl ester (Octocrylene^®), in combination with esters of cin- namic acid, preferably 4-methoxycinnamic acid-2-ethylhexyl ester and/or 4-methoxycinnamic acid propyl ester and/or 4-methoxycinnamic acid isoamyl ester. Combinations such as these are advantageously combined with water-soluble filters such as, for example, 2- phenylbenzimidazole-5-sulfonic acid and alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium and glucammonium salts thereof.

Secondary sun protection factors

Besides the groups of primary sun protection factors mentioned above, secondary sun protec- tion factors of the antioxidant type may also be used. Secondary sun protection factors of the antioxidant type interrupt the photochemical reaction chain which is initiated when UV rays penetrate into the skin. Typical examples are amino acids (for example glycine, histidine, tyrosine, tryptophane) and derivatives thereof, imidazoles (for example urocanic acid) and deriva- tives thereof, peptides, such as D,L-camosine, D-carnosine, L-carnosine and derivatives thereof (for example anserine), carotinoids, carotenes (for example alpha-carotene, beta- carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, liponic acid and derivatives thereof (for example dihydroliponic acid), aurothioglucose, propyl- thiouracil and other thiols (for example thioredoxine, glutathione, cysteine, cystine, cystamine and glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, alpha- linoleyl, cholesteryl and glyceryl esters thereof) and their salts, dilaurylthiodipropionate, distearylthiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (for example butionine sulfoximines, homocysteine sulfoximine, butionine sulfones, penta-, hexa- and hepta-thionine sulfoximine) in very small compatible dosages, also (metal) chelators (for example alpha- hydroxyfatty acids, palmitic acid, phytic acid, lactoferrine), alpha-hydroxy acids (for example citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (for ex- ample linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives thereof (for example ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (for example vitamin E acetate), vitamin A and derivatives (vitamin A palmitate) and coniferyl benzoate of benzoin resin, rutinic acid and derivatives thereof, glycosyl rutin, ferulic acid, furfurylidene glucitol, car- nosine, butyl hydroxytoluene, butyl hydroxyanisole, nordihydroguaiac resin acid, nordihy- droguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, mannose and derivatives thereof, superoxide dismutase, zinc and derivatives thereof (for example ZnO, ZnSO₄), selenium and derivatives thereof (for example selenium methionine), stilbenes and derivatives thereof (for example stilbene oxide, trans-stilbene oxide) and derivatives of these active substances suitable for the purposes of the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids).

Biogenic agents

In the context of the invention, biogenic agents are, for example, tocopherol, tocopherol acetate, tocopherol palmitate, ascorbic acid, (deoxy)ribonucleic acid and fragmentation products thereof, β-glucans, retinol, bisabolol, allantoin, phytantriol, panthenol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, plant extracts, for example prune extract, bam- bara nut extract, and vitamin complexes. Anti-microbial agents

Suitable anti-microbial agents are, in principle, all substances effective against Gram-positive bacteria, such as, for example, 4- hydroxybenzoic acid and its salts and esters, N-(4- chlorophenyl)-N'-(3,4- dichlorophenyl)urea, 2,4,4^l-trichloro-2'-hydroxy-diphenyl ether (tri- closan), 4-chloro-3,5-dimethyl-phenol, 2,2'-methylenebis(6-bromo-4- chlorophenol), 3-methyl- 4-(l-methylethyl)phenol, 2-benzyl-4-chloro-phenol, 3-(4-chlorophenoxy)-l,2-propanediol, 3- iodo-2-propynyl butylcarbamate, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrances, thymol, thyme oil, eugenol, oil of cloves, menthol, mint oil, farnesol, phenoxyetha- nol, glycerol monocaprate, glycerol monocaprylate, glycerol monolaurate (GML), diglycerol monocaprate (DMC), salicylic acid N-alkylamides, such as, for example, n-octylsalicylamide or n- decylsalicylamide.

Film formers

Standard film formers are, for example, chitosan, microcrystalline chitosan, quaternized chito- san, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives, collagen, hyaluronic acid and salts thereof and similar compounds.

Hvdrotropes

In addition, hydrotropes, for example ethanol, isopropyl alcohol or polyols, may be used to improve flow behaviour. Suitable polyols preferably contain 2 to 15 carbon atoms and at least two hydroxyl groups. The polyols may contain other functional groups, more especially amino groups, or may be modified with nitrogen. Typical examples are

• glycerol;

• alkylene glycols such as, for example, ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, hexylene glycol and polyethylene glycols with an average molecular weight of 100 to 1000 Dalton;

• technical oligoglycerol mixtures with a degree of self-condensation of 1.5 to 10, such as for example technical diglycerol mixtures with a diglycerol content of 40 to 50% by weight;

• methylol compounds such as, in particular, trimethylol ethane, trimethylol propane, trimethylol butane, pentaerythritol and dipentaerythritol; • lower alkyl glucosides, particularly those containing 1 to 8 carbon atoms in the alkyl group, for example methyl and butyl glucoside;

• sugar alcohols containing 5 to 12 carbon atoms, for example sorbitol or mannitol,

• sugars containing 5 to 12 carbon atoms, for example glucose or sucrose;

• amino sugars, for example glucamine;

• dialcoholamines, such as diethanolamine or 2-aminopropane-l,3-diol.

Preservatives

Suitable preservatives are, for example, phenoxyethanol, formaldehyde solution, parabens, pentanediol or sorbic acid and the other classes of compounds listed in Appendix 6, Parts A and B of the Kosmetikverordnung ("Cosmetics Directive").

Perfume oils

Suitable perfume oils are mixtures of natural and synthetic perfumes. Natural perfumes include the extracts of blossoms (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (anise, coriander, caraway, juniper), fruit peel (berga- mot, lemon, orange), roots (nutmeg, angelica, celery, cardamom, costus, iris, calmus), woods (pinewood, sandalwood, guaiac wood, cedarwood, rosewood), herbs and grasses (tarragon, lemon grass, sage, thyme), needles and branches (spruce, fir, pine, dwarf pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Animal raw materials, for ex- ample civet and beaver, may also be used. Typical synthetic perfume compounds are products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. Examples of perfume compounds of the ester type are benzyl acetate, phenoxyethyl isobutyrate, p-tert.butyl cyclo- hexylacetate, linalyl acetate, dimethyl benzyl carbinyl acetate, phenyl ethyl acetate, linalyl ben- zoate, benzyl formate, ethylmethyl phenyl glycinate, allyl cyclohexyl propionate, styrallyl propionate and benzyl salicylate. Ethers include, for example, benzyl ethyl ether while aldehydes include, for example, the linear alkanals containing 8 to 18 carbon atoms, citral, citronel- IaI, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal. Examples of suitable ketones are the ionones, D-isomethylionone and methyl cedryl ketone. Suitable alcohols are anethol, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol. The hydrocarbons mainly include the terpenes and balsams. However, it is preferred to use mixtures of different perfume compounds which, together, produce an agreeable perfume. Other suitable perfume oils are essential oils of relatively low volatility which are mostly used as aroma components. Examples are sage oil, camomile oil, clove oil, melissa oil, mint oil, cinnamon leaf oil, lime-blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil, ladanum oil and lavendin oil. The following are preferably used either individually or in the form of mixtures: bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, hexylcinnamaldehyde, geraniol, benzyl acetone, cyclamen aldehyde, Ii- nalool, Boisambrene Forte, Ambroxan, indole, hedione, sandelice, citrus oil, mandarin oil, orange oil, allylamyl glycolate, cyclovertal, lavendin oil, clary oil, damascone, geranium oil bourbon, cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, Fixolide NP, evernyl, iraldein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romillat, irotyl and floramat.

Dyes

Suitable dyes are any of the substances suitable and approved for cosmetic purposes as listed, for example, in the publication "Kosmetische Farbemittel" of the Farbstoflkommission der Deutschen Forschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, pages 81 to 106. Examples include cochineal red A (CI. 16255), patent blue V (CI. 42051), indigotin (CI. 73015), chlorophyllin (CI. 75810), quinoline yellow (CI. 47005), titanium dioxide (CI. 77891), indanthrene blue RS (CI. 69800) and madder lake (CI. 58000). Luminol may also be present as a luminescent dye. These dyes are normally used in concentrations of 0.001 to 0.1% by weight, based on the mixture as a whole.

The total percentage content of auxiliaries and additives may be from 1 to 50% by weight and is preferably from 5 to 40% by weight, based on the particular composition. The compositions may be produced by standard hot or cold processes.

The compositions according to the present invention are, however, not limited to the treatment of psoriasis, but are also useful for the treatment of eczema and inflammatory diseases of the skin, like contact dermatitis, atopic dermatitis or seborrheic dermatitis. The following examples are intended to illustrate the invention in more detail:

Examples

Example 1

Preparation of a spray composition comprising thiamine chloride in a concentration of 50 % w/v. 40 g of hydrogenated lecithin and 1.5 g cholesterol were heated in a small volume of etha- nol and treated with 0.8 g of tocopherol mixture. In the warmth and under agitation 1000 ml of a solution containing 1.5 g of sodium methylhydroxybenzoate, 0.2 g sodium propylhydroxy- benzoate and 20 g glycerol was added. After the evaporation of the solvent 500 g of thiamine chloride were added to obtain a thin film suspension applicable for cosmetics by spraying with a mechanical pump.

Example I/A

Preparation of a spray composition comprising thiamine chloride in a concentration of 10 % w/v. Following the preparation of example 1 the amount of thiamine chloride was reduced to 100 g.

Example 1/B

Preparation of a spray composition comprising thiamine chloride in a concentration of ^'30 % w/v. Following the preparation of example 1 the amount of thiamine chloride was reduced to 300 g.

Example 2

Preparation of a gel composition comprising thiamine chloride in a concentration of 50 % w/v using carbomer as a gelling agent. 40 g of hydrogenated lecithin and 1.5 g cholesterol were heated in a small volume of ethanol and treated with 0.8 g of a tocopherol mixture. In the warmth and under agitation 1000 ml of a solution containing 1.5 g of sodium methylhydroxybenzoate, 0.2 g sodium propylhydroxybenzoate and 20 g glycerol was added. After the evaporation of the solvent 100 g of carbomer were added. After neutralization of the pH with sodium hydroxide 500 g of thiamine chloride were added in order to obtain an applicable fluid gel in form of a thin film by means of a dispenser. Example 2/ A

Preparation of a gel composition comprising thiamine chloride in a concentration of 10 % w/v. Following the preparation of example 2 the amount of thiamine chloride was reduced to 100 g.

Example 2/B

Preparation of a gel composition comprising thiamine chloride in a concentration of 30 % w/v. Following the preparation of example 2 the amount of thiamine chloride was reduced to 300 g.

Example 3

Preparation of a gel composition comprising thiamine chloride in a concentration of 50 % w/v using hydroxy ethyl cellulose as a gelling agent. 0.2 g methyl hydroxybenzoate, 1.5 g sodium propyl hydroxybenzoate and 20 g glycerol were heated with 1000 ml water, than 0.2 g vegetable collagen and 1O g ethyl hydroxy cellulose were added. Once the stirred mixture be- came homogenous, 500 g of thiamine chloride was added to obtain an applicable fluid gel in form of a thin film by means of a dispenser.

Example 3/A

Preparation of a gel composition comprising thiamine chloride in a concentration of JO % w/v. Following the preparation of example 3 the amount of thiamine chloride was reduced to 100 g.

Example 3/B

Preparation of a gel composition comprising thiamine chloride in a concentration of ^' 30 % w/v. Following the preparation of example 3 the amount of thiamine chloride was reduced to 300 g. Example 4

Preparation of an aqueous lotion comprising thiamine chloride in a concentration of 50 % w/v. In 100 m 1 water 50 g thiamine chloride, 20 g glycerol and 14 g propylene glycol were dissolved.

Example 4/A

Preparation of an aqueous lotion comprising thiamine chloride in a concentration of 10 % w/v. Following the preparation of example 4 the amount of thiamine chloride was reduced to 1O g.

Example 4/B

Preparation of an aqueous lotion comprising thiamine chloride in a concentration of 30 % w/v. Following the preparation of example 4 the amount of thiamine chloride was reduced to 30 g.

Example 5 Preparation of an aqueous/alcoholic lotion comprising thiamine chloride in a concentration of 50 % w/v. 1O g glycerol and 1O g of propylene glycol were dissolved at 70 ⁰C in 20 ml of ethanol. Subsequently, 80 ml of distilled water and 50 g thiamine chloride were added.

Example 5/A

Preparation of an aqueous/alcoholic lotion comprising thiamine chloride in a concentration of 10 % w/v. Following the preparation of example 5 the amount of thiamine chloride was reduced to 10 g.

Example 5/B

Preparation of an aqueous/alcoholic lotion comprising thiamine chloride in a concentration of 30 % w/v. Following the preparation of example 5 the amount of thiamine chloride was re- duced to 30 g. Example 6

Preparation of a W/O emulsion comprising thiamine chloride in a concentration of 50 % w/v. 50 g General^® 122 (soy sterols), 50 g General^® 122 E5 (PEG-5 Soy Sterols), 50 g Cutina^® BW (Glycerylhydroxysterate/Cetyl Palmitate/Microcrystalline Waxes/Trihydroxysterine), 30 g petrolatum, 80 g Cetiol^® SN (Cetearyl Isononanoate), 0.5 g Butyl Hydroxytoluene (BHT), 6 g Phenonip^®(Phenoxyethanol/Methylparaben/Ethylparaben/Propylparaben/Butylparaben) were mixed at a temperature of 85 ⁰C. The aqueous phase consisting of 683.5 g of demineralised water and 50 g glycerol was preheated to 75 ⁰C and added to the oil phase under agitation to effect solubilisation. Once the mixture thus obtained has cooled down to room temperature 500 g thiamine chloride were added to obtain an applicable cosmetic emulsion in form of a thin film by means of a dispenser.

Example 6/A

Preparation of a W/O emulsion comprising thiamine chloride in a concentration of 10 % w/v. Following the preparation of example 6 the amount of thiamine chloride was reduced to 100 g.

Example 6/B

Preparation of a W/O emulsion comprising thiamine chloride in a concentration of ^'30 % w/v. Following the preparation of example 6 the amount of thiamine chloride was reduced to 300 g.

Example 7

Preparation of an O/W emulsion comprising thiamine chloride in a concentration of 50 % w/v. 40 g of Estol^® GMM 8650 (Glyceryl Myristate), 4 g of Cetyl alcohol, 50 g of Isopropyl myristate, 50 g vaseline, 2.5 g of MPOB/PPOB (70/30) mixture (Methylpara- ben/Propylparaben), 8 g Amphisol^® K (Potassium Cetyl Phosphate) were mixed at a temperature of 85 ⁰C. The aqueous phase consisting of 560.5 g of demineralised water, 200 g Car- bopol^® 1382 (1 % b.w. solution; branched acrylate/C 10-30 alkyl acrylate co-polymer), 60 g propylene glycol, 20 g glycerol and 5 g KOH (10 % b.w. aqueous solution) was preheated to 75 ⁰C and added to the oil phase under agitation to effect solubilisation. Once the mixture thus obtained has cooled down to room temperature 500 g thiamine chloride were added to obtain an applicable cosmetic emulsion in form of a thin film by means of a dispenser. Example 7/ A

Preparation of an O/W emulsion comprising thiamine chloride in a concentration of 10 % w/v. Following the preparation of example 7 the amount of thiamine chloride was reduced to 100 g.

Example 7/B

Preparation of an O/W emulsion comprising thiamine chloride in a concentration of 30 % w/v. Following the preparation of example 7 the amount of thiamine chloride was reduced to 30O g.

Examples of compositions for oral administration comprising vitamin Bl

Example 8 Caps of vitamin Bl

Example 9 Multivitamin composition

Example 10 Dietetic supplement for the skin

Example 11 Adjuvant for the therapy of Psoriasis

Example 12 Antioxidant

Example 13 Sterile Composition

The compositions consist of 0.5/1.0/2.0 g of thiamine. The respective amounts of thiamine (from sealed containers, melted in the moment of use) were mixed with 5 ml of sterile distilled water.

Example 14 Microcapsules

1O g thiamine chloride, 1 g tocopherol, 1 g benzoyl peroxide and 1 g salicylic acid were dissolved at 70 ⁰C in 150 ml distilled water. The mixture was treated with 20 g sodium alginate and stirred for 5 minutes. Once the mixture became homogenous it was dropped into a 10 % w/v aqueous solution of chitosan. Initially coazervation took place and capsules having an average diameter of 0.01 to 5 mm were formed. The capsules were filtrated from the aqueous solution and brought into a bath of calcium chloride (5 % b.w. in water) for hardening the shell. After 10 min of gentle agitation they were once again filtrated, washed and re-suspended in water to give a 5 % b.w. suspension.

In the following Table 1 some further cosmetic compositions are given in order to illustrate the scope of the present invention:

Table 1 Cosmetic compositions

Claims

1. Compositions for the treatment of psoriasis, eczema and inflammatory conditions of the skin comprising as an active ingredient a therapeutic effective amount of thiamine or its cosmetically and/or toxicologically acceptable salts.

2. Compositions according to claim 1, characterised in that they comprise thiamine or its cosmetically acceptable salts in a concentration of at least 10 to at least 60 % b.w.

3. Compositions according to claims 1 and/or 2, characterised in that they comprise

a. thiamine or its cosmetically acceptable salts, b. anti-inflammatory ingredients and/or c. carriers and/or excipients.

4. Compositions according any of the claims 1 to 3, characterised in that they comprise

(a) 10 to 60 % b.w. thiamine or its cosmetically acceptable salts,

(b) 0 to 20 % b.w. anti-inflammatory ingredients and/or

(c) 0 to 20 % b.w. carriers and/or excipients

with the condition that the amounts add optionally together with water and additional cosmetic ingredients to 100 % b.w.

5. Compositions according to any of the claims 1 to 4, characterised in that the antiinflammatory ingredients are selected from the group consisting of salicylic acid, glyzyrrhetinic acid, conjugated linoleic acid, benzoyl peroxide, chitosan, Vitamin B6 and plant actives.

6. Compositions according to any of the claims 1 to 5, characterised in that the administration is conducted topical, oral or parenteral.

7. Compositions according to any of the claims 1 to 6, characterised in that they represent creams, lotions, gels, ointments, emulsions or sprays.

8. Compositions according to any of the claims 1 to 7, characterised in that they are encapsulated.

. Use of thiamine or its non-toxic salts for the preparation of a medicament for the treatment of psoriasis, eczema and inflammatory diseases of the skin.

10. Use according to claim 9, characterised in that the thiamine or its non-toxic salt is present in an amount of at least 10 to at least 60 % b.w. in the medicament.