Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – At least one aryl ring which is part of a fused or bridged...
Reexamination Certificate
1997-07-03
2001-02-20
Reddick, Judy M. (Department: 1700)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
At least one aryl ring which is part of a fused or bridged...
C252S182180, C252S182290, C524S295000, C524S296000, C524S315000, C524S317000, C524S555000, C524S773000, C524S776000, C526S298000, C558S443000
Reexamination Certificate
active
06191202
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention is directed to alkyl cyanoacrylate compositions which are specifically formulated for topical application onto intact or broken human skin. The compositions of this invention are further formulated for single or repeated/intermittent use and are resistant to premature polymerization.
2. State of the Art
Cyanoacrylates are well known in the art and can be represented by formula I:
wherein R is an alkyl or other suitable substituent. Such cyanoacrylates are disclosed in U.S. Pat. Nos. 3,527,224; 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826. Typically, when applied onto living tissue, the R substituent is alkyl of from 2 to 10 carbon atoms and most often is butyl (e.g., n-butyl).
Suggested uses for alkyl cyanoacrylate compositions include their use in topical application onto intact skin in order to form a polymer layer which inhibits blister and pressure ulcer formation as described in U.S. Pat. No. 5,306,490 and U.S. patent application Ser. No. 08/082,927 U.S. Pat. No. 5,403,591. Still other suggested uses includes inhibiting irritation arising from prosthetic devices as described in U.S. patent application Ser. No. 08/200,953 as well as inhibiting skin irritation and infection due to incontinence as described in concurrently filed U.S. patent application Ser. No. 08/299,935, U.S. Pat. No. 5,580,565, entitled “USE OF CYANOACRYLATE ADHESIVES FOR PROVIDING A PROTECTIVE BARRIER FILM FOR THE SKIN”. The disclosures of such patent and patent applications being incorporated herein by reference in their entirety. When so employed, the cyanoacrylate adhesive composition is applied topically onto intact skin and, after curing, a cyanoacrylate polymer coating is formed which coating adheres strongly to the skin.
Other uses of alkyl cyanoacrylates include their use with small wounds as described in U.S. patent application Ser. No. 08/231,638 where the cyanoacrylate composition is applied onto the surface of a topical wound (one which does not penetrate the dermal layer) where, after curing, a protective coating or layer is formed over the wound. The disclosure of this application is also incorporated herein by reference in its entirety.
Ideally, for topical applications as recited above, the alkyl cyanoacrylate compositions should meet as many of the following criteria as possible:
(1) the alkyl cyanoacrylate composition should be formulated to be stable against premature polymerization. Such formulations would therefore be suitable for storage in applicators for multiple use applications and in spray applicators where unintended polymerization can clog the spray mechanism;
(2) the alkyl cyanoacrylate composition should be of suitable viscosity for desired application onto the skin;
(3) once applied to the skin, the alkyl cyanoacrylate should not polymerize so quickly as to generate sufficient heat as to impart a “burning” sensation to the patient but should cure within from about 10 seconds to about 1 minute after application;
(4) the resulting cured polymer should possess sufficient flexibility such that the integrity of the polymer coating is not compromised by, for example, cracking, etc;
(5) the resulting cured polymer should possess sufficient durability such that the polymer does not prematurely shed from the patient's skin; and
(6) is non-toxic when applied to skin.
In contrast to topical applications, it is also known that alkyl cyanoacrylate compositions can be employed in surgical environments as suture replacements or hemostats. When employed in these environments, the parameters of the alkyl cyanoacrylate composition for such applications often diverge from the compositional parameters for topical application. For example, unlike topical application over large areas of skin, surgical application of the alkyl cyanoacrylate composition is typically over very specific, small total surface area internal parts of the human body and, accordingly, parameters such as viscosity, curing time, flexibility, durability, etc., are often different for this application as opposed to the parameters required for topical application. Accordingly, while it is recognized in the Robertson, et al., U.S. Pat. No. 3,722,599 to combine a polymerization inhibitor, a thickener, and a plasticizer with a fluoroalkyl cyanoacrylate, these compositions are disclosed for use as suture replacements or as hemostats and such compositions are not always suitable for topical application onto the skin surface.
SUMMARY OF THE INVENTION
This invention is directed to novel alkyl cyanoacrylate compositions suitable for topical application to human skin. The compositions of this invention are characterized by the use of both a specific polymerization inhibitor and amount of this inhibitor which effectively inhibits both premature and too rapid polymerization of the cyanoacrylate adhesive component of the composition and by the use of a critical amount of a plasticizer so as to maintain the integrity of the polymer over the skin surface. In a preferred embodiment, the composition further comprises a suitable amount of a thickening agent to provide for a compositional viscosity suitable for certain applications onto human skin.
Specifically, in a first composition aspect, this invention is directed to an alkyl cyanoacrylate composition which comprises
(a) from about 75 to 82 weight percent of an alkyl cyanoacrylate;
(b) from about 50 to 500 parts per million of SO
2
as a polymerization inhibitor; and
(c) from about 18 percent to about 25 percent by weight of a biocompatible plasticizer
wherein the alkyl cyanoacrylate, in monomeric form, is represented by formula I:
where R is alkyl of 2 to 10 carbon atoms.
In a second composition aspect, this invention is directed to an alkyl cyanoacrylate composition which comprises
(a) from about 75 to 80 weight percent of n-butyl cyanoacrylate;
(b) about 200 parts per million of SO
2
as a polymerization inhibitor; and
(c) from about 20 percent to about 25 percent by weight of a dialkyl phthalate independently having from 1 to 10 carbon atoms in each alkyl group
wherein the n-butyl cyanoacrylate, in monomeric form, is represented by formula I:
In the compositions of this invention, an amount of a biocompatible plasticizer of from about 18 to about 25 weight percent is essential to provide for a polymer coating (film formation) having the requisite degree of flexibility for the resulting polymer coating such that the coating does not crack upon movement of the skin area to which it was applied while also maintaining suitable durability in the polymer coating and an adequate curing time of from about 10 to 60 seconds. In a preferred embodiment, the biocompatible plasticizer is employed from about 20 to 25 weight percent based on the total weight of the alkyl cyanoacrylate composition.
Likewise, it has been found that the use of from 50 to 500 ppm of SO
2
as the polymerization inhibitor is essential in providing for an alkyl cyanoacrylate composition having a curing time which is neither too fast (i.e., less than about 10 seconds) so as to cause a “burning” sensation when applied to the skin nor too slow (greater than 60 seconds) as to interfere with effective application. Additionally, as opposed to other polymerization inhibitors such as methane sulfonic acid, sulfur dioxide is biocompatible with topical application onto human skin and does not produce discernible skin irritation when employed in the amounts recited herein.
In a preferred embodiment, the alkyl cyanoacrylate composition of this invention further comprises a sufficient amount of a thickening agent to provide for a viscosity of from about 2 to 50,000 centipoise at 20° C. The thickening agent employed is any biocompatible material which increases the viscosity of the alkyl cyanoacrylate composition and includes, by way of example, a partial polymer of the alkyl cyanoacrylate, polymethyl methacrylate (PMMA) or other preformed polymers soluble in the alkyl cyanoacrylate, a suspending agent such as fumed silica, and the like with PPMA b
Barley Leonard V.
Byram Michael M.
Greff Richard J.
Tighe Patrick J.
Burns Doane , Swecker, Mathis LLP
MedLogic Global Corporation
Reddick Judy M.
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