Protective Composition for Users of Cyanoacrylate Adhesives

EP 0080172 B1 Européiisches Patentamt o> European Patent Office Office européen des brevets ® Publication number: 0080172 B1 ® EUROPEAN PATENT SPECIFICATION @ Date of publication of patent specification: 22.07.87 ® int CL43 A 61 K 7/40 (2) Application number: 82110658.0 Q2) Date offiling: 13.11.32 ® Protective composition for users of cyanocrylate adhesives. ® Proprietor: PASCALE LIMITED 51/52 Fitzwilliam Square Dublin 2 (IE) @ Priority: 24.11.31 IE 2753/31 I ® Date of publication of application: 01.06.83 Bulletin 83/22 ® Inventor: O’Sullivan, Donncha 6 Greenfield Crescent @ Publication of the grant of the patent: D°"nYb|'00k. Dublin 4 HE) 22.07.87 Bulletin 87/30 Representative: Hansen, Bernd, Dr.rer.nat. et al Hoffmann, Eitle & Partner Patentanw'a'lte Arabellastrasse 4 D-8000 Mfmchen 81 (DE) Designated Contracting States: DE FR GB IT NL SE (SE References cited: US-A-4 066 589 Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European patent convention). Courier Press, Leamington Spa, England. 70 I5 20 25 30 35 40 45 50 55 B0 65 0 080 1 72 Description This invention relates to precaution against a hazard in the use of adhesive compositions based on cyanoacrylate monomers. It relates to a protective composition for the skin (especially the hands) of a person working with a cyanoacrylate adhesive or "superglue”, and to a method using the composition, for protecting such a person's skin. Cyanoacrylate monomers, as is well known, polymerise rapidly on contact with certain activating substances in trace quantities. These substances include inorganic salts, carbonyl compounds such as urea, and Lewis bases such as water. Human perspiration comprises mainly moisture, a small proportion of urea, inorganic salts, and some lactic acid. Human skin normally has a slightly acid reaction, with a pH of 5 to 6. Normal human skin serves as a very effective activating substrate for cyanoacrylate adhesives. There thus arises the notorious hazard involved in the use of these compositions, that traces of the composition on the skin are immediately activated, and skin so contaminated will on contact stick fast to other skin portions or substrate surfaces, with initial cu re taking place within a few seconds. Persons thus affected may have great difficulty in freeing themselves, and in severe cases may even require surgical assistance. The problem is well known in factories where parts are assembled by means of ”superglues” and the like, but the hazard is perhaps greater when inexperienced persons are handling cyanoacrylates. It is an object of this invention to provide an easily used protective means to render cyanoacrylate adhesives innocuous to persons using them. Accordingly the invention provides a protective composition for the skin of a person working with a cyanoacrylate-type adhesive, comprising an active ingredient incorporated in a dermatologically compatible base adapted for topical application, characterised in that the active ingredient is an effective amount of a skin-compatible adhesion-inhibiting substance for cyanoacrylate monomers selected from conventional stabilizers for cyanoacrylate monomers and zwitterionic aminosulfonic acids having a pK,., at 20°C in the range 6.0 to 8.3. The adhesion-inhibiting substance may be a skin-compatible conventional stabiliser for cyanoacrylate monomers, but in a preferred embodiment of the invention, said substance comprises at least one zwitterionic aminosulphonic acid (hereinafter ZASA) having a pK,., at 20°C in the range 6.0-8.3 (i.e. the molecules of the substance exist mainly in their dipolar form in the pH range 6.0-8.3). These ZASA’s permit polymerisation of the adhesive but, surprisingly, they render the resulting solid non-adherent to the skin, so that it can be easily peeled, rubbed or washed off. The ZASA’s so far investigated and found to have the properties necessary for use in compositions of the invention are set out, with their pKa values and trivial names, in the following list (all pKa values quoted in this specification are at 20°C): I 2-(N-Morpholiny|)—ethane sulphonic acid 6.15 MES N,N-bis-(2-Hydroxyethyl)-2-aminoethane sulphonic acid 7.15 BES 2-[N-(N’-2-Hydroxyethyl)-piperazinyl]-ethane sulphonic acid 7.55 HEPES 3-[N-(N’-2-Hydroxyethyl)-piperazinyl]-propane sulphonic acid 8.0 HEPPS (or EPPS) Piperazine-1,4-bis-(2—ethane sulphonic acid) 6.8 PIPES 2-[N-tris-(Hydroxymethyl)-methylamino]-ethane sulphonic acid 7.5 TES All of them but HEPPS were described among others, by Good N. et al. in Biochemistry 1966, Vol 5, 467. "it is not difficult to synthesise aliphatic amines with appropriate acid dissociation constants”—to quote from the above—cited report. It may be added that the preparation of their aromatic analogues presents no particular difficulty either. To quote further from the report: ’’It is easy to design and prepare a wide variety of inexpensive compounds" (i.e., hydrogen ion buffers for biological research) "with desired dissociation constants, solubilities and reactivities... Many more could be prepared...". All such easily accessible ZASA’ , having pK,., values within the above specified limits, are accordingly to be understood at suitable for use in compositions of the present invention, unless disqualified by dermatological incompatibility which, however, is thought to be unlikely. The proportion of the active ingredient by weight of the composition is in the range 0.05% to 30%, preferably 0.05% to 5.0%, most preferably 0.1% to 1.0%. The topical base is selected from a wide variety of compositions formulated according to known principles for protective, cosmetic and pharmaceutical purposes. Such compositions include creams, solids, lotions and film-forming solutions among others. They may be presented in boxes, jars or squeezable tubes, both collapsible and non-collapsible. The solids may be presented as sticks for rubbing on to the skin. Some of the topical bases may be presented as papers, woven or non-woven fabric pieces, or pads, all impregnated with the composition. 0 080 1 72 The invention will be appreciated in greater detail from the following examples of specific embodiments thereof. Example 1 5 A skin cream is made up from the following recipe: A. Oil phase Parts by weight Stearic acid 13.0 Microcrystalline wax 6.5 70 O"Ve O“ 3.5 Glyceryl monostearate (acid-stable grade) 3.5 Polyoxyethylene sorbitan monolaurate‘ 12.0 Silicone fluid (200—350 centistokes) 3.0 ,5 B. Aqueous phase Parts by weight HEPES 0.2 Water (q.s. ad 100.0) 58.3 ‘The product sold under the trade name TWEEN® 20 This cream is rubbed into the hands before working with a cyanoacrylate adhesive composition. It will normally give protection against sticking of the fingers together or to an object being glued, for a working session of 4-5 hours. It is non-greasy and confortable to use. 20 25 Example 2 An application stick is made from the following ingredients: Parts by weight 30 Eutanol G‘® 39.0 Comperlan HS‘® 11.0 Stearic acid 10.0 HEPPS 5.0 Ethanol 96% v/v ' 20.0 35 Glycerol 15.0 ‘Henkel International, Federal Republic of Germany. The ingredients other than ethanol are mixed and melted together. The temperature of the melt is brought below 70°, whereupon the ethanol is added and well mixed in. The melt is poured into suitable 40 moulds and allowed to set. The resulting moulded sticks are removed from the moulds, wrapped individually in aluminium foil and packed. A stick is rubbed on the hands before working with a cyanoacrylate adhesive composition. The protection period is similar to that given by the compositions of the previous Example. 45 Example 3 This example illustrates a typical formulation which can be used for preparing a protective composition in accordance with the invention, using any zwitterionic substances ("ZASA's”) which have suitable properties, including those mentioned in the present specification. 50 Ingredient Parts by weight Stearic acid 10.05 Vegetable oil (e.g. Sunflower) 8.0 Glyceryl monostearate (self-emulsifying) 2.50 55 Silicone oil (DC Silicone 200/350, Dow Corning) 0.50 TWEEN® 20 (Polyoxyethylene sorbitan monolauratel 10.40 The selected ”ZASA" 0.10 to 1.00* Water (q.s. ad 100) 68.45 to 67.55 50 *A preferred proportion here is 0.55. The ingredients are put together by known pharmaceutical procedures, such as those set out in the previous examples. In addition to preservatives, other conventional pharmaceutically acceptable additives may be 55 incorporated in the compositions of the invention. These include, for example, humectants, film formers 70 15 20 25 30 35 40 45 50 55 60 65 0 080 172 and water repellants. Sorbitol is a useful humectant. A 4% mucilage of Methyl cellulose is a useful film former. The dimethyl silicones sold by Imperial Chemical Industries Ltd. of the UK under the trade designations F 110 and F 111, are useful water repellents. Compositions of the invention, when applied to a person's skin, prevent sl