Patentamt JEuropaisch.esEuropean Patent Office ® Publication number: 0 002 426 Office europeen des brevets A1 © EUROPEAN PATENT APPLICATION @ Application number: 78850022.1 (g) Int. CI.2: A 61 K 7/32 (S) Date of filing: 01.12.78 (30) Priority: 01.12.77 SE 7713617 0 Applicant: Astra-Gemaverken Aktiebolag Box 209 S-791 01 Falun(SE) (35) Date of publication of application: 13.06.79 Bulletin 79/12 (72) Inventor: Broberg, Berndt Fredrik Julius Byvagen 48 (S) Designated contracting states: S-151 52 S6dertalje(SE) BE CH DE FR GB IT LU NL SE (72) Inventor: Evers, Hans Christer Arvid Hovslagarvagen 17 S-151 59 S6dertalje{SE) (72) Inventor: Juhlin, Lennart August Albert Dobelnsgatan 30 H S-752 37 Uppsala(SE) (74) Representative: Wurm, Bengt Runio et al. Patent and Trade Mark Department Ab Astra S-151 85 Sodertalje(SE) @ Antiperspirant. The present invention relates to antiperspirants which shall have a rapid onset in order to obtain an immediate inhibition of perspiration. The invention thereby relates to antiperspirants which comprise a local anesthetic agent, whereby the invention is characterized in that the antipers- pirant comprises a local anesthetic agent of the group prilocaine, bensocaine, lidocaine, bupivacaine, mepivacaine, etidocaine, ketocaine, 2-(2-n-butyloxyphenoxy)-1- diisopropylaminoethane, tetracaine, butanilicaine, trime- caine, dibucaine, quinisocaine, butacaine, oxybuprocaine and toylcaine. Preferred compositions comprises a mixture of prilocaine, tetracaine, butanilicaine, and trimecaine in the form of its base and one of the compounds bensocaine, lidocaine, bupivacaine, mepivacaine, dibucaine, and etido- caine, as well as tetracaine, butanilicaine and trimecaine. The antiperspirant is to be used elsewhere on a body where excessive perspiration occurs, preferably in axillae and on the hands. The present invention relates to an antiperspirant compo- sition. The object of the present invention is to obtain an antiper- spirant composition which gives a real blockade of the function of the sweat glands preferably in the axillae. In most commercial perspirant inhibiting cosmetics present on the market the active perspirant inhibiting component is usually an adstrinfent salt of aluminium, zink, zikonum or a rare earth metal. Such salts are as a rule not immediately active as antiperspirants after the first tratemt but re- quire a number of treatments during a time period until a desired degree of antiperspiration effect can be obtained. Depending on these problems investigation have been carried out in order to find compounds which have the rapid antiper- spiration effect without requiring a number of trsotments in order to obtain useful antiperspiration effect, which compounds are innocouos to clothes and skin as well. Diffe- rent anticholinergic compounds have been used, too, which prevent the stimulation of the ecrine sweat-glands by in- hibiting the action of acetylcholine. Further it is previously known as disclosed in Swedish Patent Specification S/N 7200316-3 (publ.no. 381 567) to use 3-phenyl- -carbo(β-diethylamino)-ethoxy-2,3-dihydrobensofuran hydro- chloride, which is known to possess analgesic, hypotensive, local anesthetic, and antispasmodic effects, as an active component in antiperspirants in amounts of 0.01-2.0% of an aqueous solution. In Chemical Abstracts 71 (1969), 48238b, it has been dis- closed that procaine when administered electrophoretically possesses antihydrotic effect. However, procaine administered without electropheresis but only topical will not give any antihydrotic effect. It nas now surprisingly been found that it is possible to obtain a rapid and completely effective antiperspiration effect by means of the present invention, which i characte- rized in that the antiperspirant composition contains at least one local anesthatically active compound of the group prilocaine, benzocaine, lidocaine, bupivacaine, mepivacaine, etidocaine, ketocaine, 2-(2-n-butyloxyphenoxy)-1-diisopropyl- aminoethane, butanilicaine, trimecaine, dibucaine, tetracaine, quinisocaine, butacaine, oxybuprocaine, and tolycaine. In preferred embodiments of the invention the active substance in the form of its base is used. The active compounds can, however, form salts, preferably of such a type that is substaintially watersoluble. Such salts are salts with acids, e g hydrohalogen acids, e g hydrobromic acid, hydrochloric acid, hydroiodic acid,and in some cases hydrofluoric acid. Even if the hydrohalogenic acids are prefrred saltforming acids, which are especially useful in connection with the non-substituted compounds, different other wellknown acids able to form salts with amines can be used c g sulohuric acid, sulphuveus acid, acetic acid, phesphoric acid, boric acid, gluconic acid, and carbonic acid. Salts, which are the result of reactions with such acids or of similar saltforming material have usually a higher watersolubility than the original active compounds. An antiperspirant composition according to the present in- vention is usually administered as an emulsion containing the anesthetic active agent, an emulsifier, and/or thicke- ning agent and water and when necessary a solvent for the agent. Assuitable emulsifiers Tween® 80, Arlaton® 289, and lecitine can be used. Arlaton 289 is a polyoxyethylene fatty acid ester, and Tween® 80 is a serbitansfatty acid ester. As suitable thickening agent Carbopol , Metocel, Pluronic® and carboxymethylcellulose can be used. In certain cases the thickening agent may also have emulsi- fying properties. Thus Carbopol® and Pluronio® can be used both as thickening agent and emulsifier. As suitable solvents for the active agent alcohols having 1-6 carbon atoms, and 1-5 hydroxy groups (ethancl, propanol, isopropanol, glycerol, sorbitol, ethylene glycol, propylene glycol; polyalkylene glycols, e g polyethylene glycols (molecular weights of 300 to 10 000); moneglycerides, wherein the fatty acid componant has 12-18 carbon atoms, e g glycerol monolaurate, and other materials in order to im- prove different properties of the cosmetic preparations. Baotericides, e g hexachlorophen, fungicides and antibio- tics, e g neomyeien, can be incorporated as well. However, the antiperspirant composition can, as evident from above, consist of local anesthetic agent only, whereby then the composition is suitably a mixture of on one hand prilocaine, tetracaine, butanilicaine, and trimecaine in base form and on the other each of the compounds bensocaine, lido- caine, bupivacains, mepivacaine, dibucaine and etidocaine as well as tetracaine, butanilicaine end trimecaine in base form. These mixtures give oils which can be applied easily or a carrier, which then is applied in the axilla. Preferred suitable mixtures are prilocaine and bensocaine in the weight ratio 65:35 to 50:20, preferably 70:30; prilocaine and lidocaine in the weight ratio 42:58 to 80:20, suitably 47:53 to 62:38, preferably 55:45; prilocaine and etidocaine in the weight ratio 55:45 to 95:5, suitably 50:40 to 80:20, preferably 70:30; crilocaine and mepivacaine in the weight ratio 80:20 to 97:3, suitably 85:15 to 90:10, preferably 87:13; prilocaine and bupivacaine in the weight ratio of 72:2E to 97:3, suitably 78:22 to 88:12, preferably 85:15. An antiperspirant composition can be prepared within the following limits for components present. Above given compounds, except for bensocaine, ketocaine, and 2-(2-n-butyloxyphenoxy)-1-diisopropylaminoethane are repre- sented by the general formulae wherein R1 is and R2 is hydrogen or methyl, whereby R2 is hydrogen when R1 is Bensocaine, 4-aminobenzoic acid ethylester, has the formula Ketocaine and 2-(2-n-butyloxyphenoxy)-1-diisopropylamino- ethane are represented by the formula R3 wherein is -COC3H7 (Ketocaine) or -OC4H9. 1-methyl-2-(2,6-xylylcarbamoyl)piperidine is known under the generic name mepivacaine and is sold under the trade mark Carbocaine® 1-butyl-2-(2,8-xylylcarbamoyl)piperidine is known under the generic name bupivacaine and is sold under the trade mark Marcaine® 2-propylamino-N-(2-tolyl)propionamide is known under the generic name prilocaine and is sold under the trade mark Citanest® Diethylaminoacet-2,6-xylidide is known under the generic name lidocaine and is sold under the trade mark Cylocaine 2-ethylpropylamino-2,6-n-butyroxylidide is known under the generic name etidocaine and is sold under the trade mark Duranest® The amount of the compound of the above formula active against perspiration and present in the antiperspirant com- positions is usually 0.5-100 % by weight, preferably 0.5-10 %, and more preferably 2-5 %. Higher concentrations than these will usually not be proportionally more active than average or lower consentrotions within the renges gives When lower concentrations than the lower amounts in the ranges given are used the amount of preparation necessary to be applied in order to obtain an amount large enough of the active compound then will become so large that it is un- practical. The amounts of the compositions given which are applied at one occasion are generally such that 1 to 50 milligrams of active compound, e g lidocaine-prilocaine mixture in base form are deposited, on the place or places, usually in the axillae, to be treated. Preferably 1 to 30 mg, more pre- ferably 5 to 20 mg, are apolied. The use on other parts of the body is usually adopted so that the amount of active compound, which is applied in an amount within above given ranges, is proportional to the surface. The aqueous, water and alcohol containing or other compo- sitions of the invention in the forms of solutions, emul- sions, eremes, ointments, or in any other form are applied onto the skin at ambient temperature, preferably by means of rellton applicator or with applicator or manual rubbing in. Spraying of a composition may as well be used. The body place treated is usually the axillae, but also the chest, the bac, the seat, the arms, the palms of the hands the face, the forehead, the genital regions, the thighs and the fest can be treated. The intention gives sevenal significative advantages and provides for the production of antiperspirant compositions which are superior to the compositions now on the market in several respects.