WO9830090-1	For instance, covering small non-suturable wounds on skin surfaces with a polymeric cyanoacrylate film having a broad spectrum of antimicrobial activity would mitigate against possible wound infection.
WO9830090-2	First, the antimicrobial agent must be soluble or dispersible in the cyanoacrylate composition at the concentrations necessary to effect antimicrobial properties.
WO9830090-3	SUMMARY OF THE INVENTION This invention is directed to cyanoacrylate ester compositions comprising an antimicrobially effective amount of a complex of iodine molecules with a biocompatible polymer.
WO9830090-4	The specific antimicrobial iodine complex employed is compatible with the cyanoacrylate composition insofar as the antimicrobial complex neither causes premature polymerization nor prevents polymerization of the monomer, rather a flexible and durable polymeric film is formed in situ on mammalian skin by this composition.
WO9830090-5	Accordingly, in one of its composition aspects, this invention is directs to an antimicrobial cyanoacrylate composition which comprises : (a) a polymerizable cyanoacrylate ester;
WO9830090-6	The term"a biocompatible polymer"refers to polymers which, as iodine complexes (adducts), are compatible with in vivo applications of cyanoacrylate ester compositions onto mammalian skin including human skin. Representative polymers include polyvinylpyrrolidone, copolymers comprising polyvinylpyrrolidone which is optionally crosslinked, and the like.
WO9830090-7	The term"a complex of iodine molecules with a biocompatible polymer" refers to an antimicrobial complex formed by the addition of iodine a2) to the biocompatible polymer. Such complexes are well known in the art and the resulting complex typically comprises both available iodine and iodine anions.
WO9830090-8	Such iodine/polymer complexes are distinguished from antibiotics which are naturally derived materials from either bacteria or fungi and whose mode of action is to interfere with bacterial processes resulting in bacterial death.
WO9830090-9	A preferred iodine/polymer complex for use in the compositions of this invention is a polyvinylpyrrolidone iodine complex which is described in, for example, U. S.
WO9830090-10	As shown in the examples below, many other conventional antimicrobial agents, when added to the cyanoacrylate ester composition cause polymerization of this composition as evidenced by gel formation within 24 hours of such addition or, in the case of elemental iodine, prevent in siru polymerization of the cyanoacrylate ester composition on mammalian skin.
WO9830090-11	The iodine/polymer complex is preferably added as the commercially available solid composition rather than as the commercially available aqueous or ethanolic solution insofar as the solution can cause premature polymerization of the cyanoacrylate ester which is apparently due to solvent's effects.
WO9830090-12	Upon addition of the solid iodine/polymer complex to the cyanoacrylate prepolymer composition, the resulting system is thoroughly mixed to obtain a homogeneous suspension.
WO9830090-13	Preferably, from about 5 to about 40 weight percent of the iodine/polymer complex and more preferably from about 10 to 25 weight percent is added to the cyanoacrylate composition based on the total weight of the composition.
WO9830090-14	Zones of inhibition of at least 1 millimeter and preferably 3 millimeters from the edge of the film when tested in the manner of Example 2 below evidence that the polymeric film is antimicrobial.
WO9830090-15	The composition of the antimicrobial complex and the cyanoacrylate ester can be formulated to a specific viscosity to meet disparate demands for the intended application of the composition.
WO9830090-16	Suitable thickening agents include, by way of example, polymethyl methacrylate (PMMA) or other preformed polymers soluble or dispersible in the composition, a suspending agent such as fumed silica and the like, with PMMA being preferred.
WO9830090-17	In a particularly preferred embodiment, this inhibitor is sulfur dioxide which is employed at from about 50 to 500 ppm based on the total weight of the composition absent the antimicrobial agent.
WO9830090-18	When so employed, the in situ formed film strongly adheres to the mammalian skin surface to provide for a surgical incise drape which does not lift during surgery and has broad spectrum antimicrobial properties.
WO9830090-19	This occurs because the cyanoacrylate polymer adheres only to the uppermost portion of the epidermal layer which is continuously in the process of being sloughed off and replaced by the underlying cells.
WO9830090-20	25 In view of the many different uses for topical application onto mammalian skin, this invention also encompasses a kit of parts useful for applying the antimicrobial cyanoacrylate compositions described herein onto mammalian skin.
WO9830090-21	Such materials include, by way of example, inorganic materials such as Type 1 glass (including amber glass), ceramics, metals (e.g. , aluminum, tin and tin coated tubes), etc. and organic materials such as inert polymers including polyolefins (e.g. , high density polyethylene), fluorinated polyolefins, and the like.
WO9830090-22	The above data demonstrates that of the antimicrobial agents tested, only polyvinylpyrrolidone iodine complex was compatible with the cyanoacrylate composition and, of the polyvinylpyrrolidone iodine complexes tested, only the solid form was compatible.
WO9830090-23	Significantly, the suspension formed by the addition of solid polyvinylpyrrolidone iodine complex was curable in situ on human skin resulting in a flexible and durable polymeric film.
WO9830090-24	EXAMPLE 2 The following example was conducted to determine whether sufficient polyvinylpyrrolidone iodine complex was incorporated into the polymeric cyanoacrylate film formed in sinw to render this film antimicrobial.
WO02057288-25	bi s { [ (isopropoxycarb onyl) oxy] methyl} { [1- ( {2-amino- [6- (4-methoxyphenyl) sulfanyl]-9H-purin-9-yl} methyl)-2-methylcyclopropyl] oxy} methylphosphonate (Compound 112);