Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Cellular products or processes of preparing a cellular...
Reexamination Certificate
1998-10-15
2001-06-19
Mulcahy, Peter D. (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Cellular products or processes of preparing a cellular...
C521S074000, C521S077000, C521S152000, C521S173000, C422S001000, C422S022000, C524S296000, C524S297000
Reexamination Certificate
active
06248800
ABSTRACT:
BACKGROUND OF THE INVENTION
Field of the Invention
This invention is directed to methods for sterilizing cyanoacrylate prepolymer compositions under conditions wherein the prepolymer remains in polymerizable (non-gelled) form after sterilization. The methods of this invention employ, in part, E-bean sterilization techniques.
REFERENCES
The following patent applications and patents are cited and/or referenced in this application as superscript numbers:
1 Hawkins, et al., Surgical Adhesive Compositions, U.S. Pat. No. 3,591,676, issued on Jul. 6, 1971
2 Halpern, et al., Adhesive for Living Tissue, U.S. Pat. No. 3,667,472, issued on Jun. 6, 1972
3 McIntire, et al., Process for the Preparation of Poly(&agr;-Cyanoacrylates), U.S. Pat. No. 3,654,239, issued on Apr. 4, 1972
4 Barley, et al., Methods for Treating Non-Suturable Wounds by Use of Cyanoacrylate Adhesives, International Patent Application Publication No. WO 93/25196, published on Dec. 23, 1993
5 Barley, et al., Methods for Treating Suturable Wounds by Use of Sutures and Cyanoacrylate Adhesives, U.S. Pat. No. 5,254,132, issued on Oct. 19, 1993
6 Barley, et al., Methods for Reducing Skin Irritation From Artificial Devices by Use of Cyanoacrylate Adhesives, U.S. Pat. No. 5,653,789, issued on Aug. 5, 1997
7 Rabinowitz, et al., Method of Surgically Bonding Tissue Together, U.S. Pat. No. 3,527,224, issued on Sep. 8, 1970
8 Kronenthal, et al., Surgical Adhesives, U.S. Pat. No. 3,995,641, issued on Dec. 7, 1976
9 Davydov, et al., Medical Adhesive, U.S. Pat. No. 4,035,334, issued on Jul. 12, 1977
10 Waniczek, et al., Stabilized Cyanoacrylate Adhesives Containing Bis-Trialkylsilyl Esters of Sulfuric Acid, U.S. Pat. No. 4,650,826, issued on Mar. 17, 1987
11 Askill, et al., “Methods for Draping Surgical Incision Sites” U.S. Pat. No. 5,730,994 issued on Mar. 24, 1998
12 Stehlik, “Sterilization of Tissue Binding Adhesives”, British Patent Application Publication No. 1 281 457, published on Jul. 12, 1972
13 McDonnell, et al., “Sterilized Cyanoacrylate Adhesive Composition, and a Method of Making Such a Composition”, U.S. Pat. No. 5,530,037, issued on Jun. 25, 1996
14 Greff, et al., “Cyanoacrylate Adhesive Compositions”, U.S. Pat. No. 5,480,935, issued on Jan. 2, 1996
15 Askill, et al., “Package for Cyanoacrylate Composition”, U.S. patent application Ser. No. 09/062,514, filed on Apr. 17, 1997
16 O'Sullivan, et al., High Viscosity Cyanoacrylate Adhesive Compositions, and Process for Their Preparation, U.S. Pat. No. 4,038,345, issued on Jul. 26, 1977
17 Joyner, et al., Plasticized Monomeric Adhesive Compositions and Articles Prepared Therefrom, U.S. Pat. No. 2,784,127, issued on Mar. 5, 1957
18 Columbus, et al., Adhesive Cyanoacrylate Compositions with Reduced Adhesion to Skin, U.S. Pat. No. 4,444,933, issued on Apr. 24, 1984
19 Greff, et al., “Cyanoacrylate Compositions Comprising an Antimicrobial Agent”, U.S. Pat. No. 5,684,042, issued on Nov. 4, 1998
20 Dimiter, British Patent Application Serial No. 2 306 469A, “Sterilizing Cyanoacrylate Preparations” published Jun. 7, 1997
All of the above patent applications and patents are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent application or patent was specifically and individually indicated to be incorporated by reference in its entirety.
STATE OF THE ART
Compositions comprising cyanoacrylate esters have been disclosed as having adhesive properties suitable for a variety of human medical uses. Such uses include, for example, use as a replacement or adjunct for sutures or staples in closing the dermal layer of an incision after surgery; use as a hemostat; use in covering small non-suturable wounds on skin surfaces; use in inhibiting surface skin irritation arising from friction between the skin surface and artificial devices such as tapes, prosthetic devices, casts, etc.; and use in the in situ formation of a surgical incise drape.
1-6,11
In each case, when topically applied to mammalian skin, the cyanoacrylate rapidly polymerizes, typically within a minute, to form a coherent, adhesive, polymeric film which strongly adheres to the skin.
Cyanoacrylate esters suggested for such uses include the following structures:
wherein R is an alkyl or other suitable substituent. Such cyanoacrylate esters are disclosed in, for example, U.S. Pat. Nos. 3,527,224; 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826.
1,2,7-10
In view of the numerous medical uses of cyanoacrylate ester compositions, sterilized forms of these compositions would be particularly beneficial. In fact, it would be particularly desirable if the sterilization techniques were conducted on the packaged product so that, upon sterilization, the sterilized composition could be immediately shipped. Sterilization of the packaged product would thereby prevent reintroduction of microbial contaminants during the packaging step.
However, when applied to cyanoacrylate ester compositions, conventional sterilization techniques are often unsuitable or suffer from undesirable results. For example, it is essential that the selected sterilization technique employed does not result in polymerization of the cyanoacrylate ester and, accordingly, high temperature heat or steam sterilization techniques are contra-indicated, although Dimiter
20
reports the use of heat sterilization temperatures of at least 160° C. for these compositions. Similarly, when sterilization is conducted on packaged cyanoacrylate ester compositions, selected sterilization methods must be able to penetrate the packaging material and sterilize the entire contents of the package including the cyanoacrylate ester composition.
In point of fact, Stehlik
12
recites that normal sterilization processes such as steam-sterilization, heat sterilization, gas treatment, sterile filtration and ionizing radiation at room temperature are unacceptable because these processes result in polymerization of the cyanoacrylate ester leading to solid compositions unsuitable for use as adhesives. Stehlik goes on to disclose that sterilization of cyanoacrylate compositions can be preferably achieved by first solidifying the composition by freezing the composition at very low temperatures (−196° C. and −80° C. being disclosed in the examples) and then exposing the frozen, solidified composition to &ggr;-ionizing radiation. In this reference, radiation doses of, e.g., 1.5 Mrad of Co
60
&ggr;-radiation, were disclosed as killing bacterial spores.
It is apparent, however, that the use of low temperatures to achieve solidification of the cyanoacrylate ester composition is not practical for manufacture on an industrial scale.
McDonnell, et al.
13
also recite that most sterilization methods are unsuitable or suffer severe limitations in their applicability to cyanoacrylate compositions and, in particular, packaged cyanoacrylate compositions. In fact, this reference discloses that sterilization via electron beam (E-beam) exposure is unacceptable because E-beam accelerators have relatively low penetrating ability and would be effective only in sterilizing the outer surfaces of the package. McDonnell, et al. then recites sterilization techniques using a very high dose of &ggr;-irradiation (at least 2.5 mRad) delivered to the composition at room temperature.
However, high doses of agressively penetrating &ggr; radiation will cause changes in the formulation and attempts to minimize these changes require the addition of very high levels of inhibitors. Such high levels of inhibitors increase the toxicity of the mixture and increase the toxic by-products formed upon &ggr; irradiation. The use of high doses of toxic &ggr;-radiation to effect sterilization also raises safety concerns for workers who are exposed long term to this radiation.
SUMMARY OF THE INVENTION
This invention is directed to methods for sterilizing cyanoacrylate ester compositions. In particular, this invention is directed to the novel and unexpected result that, under carefully controlled conditions, packaged cyanoacrylate ester compositions can be sterilized us
Askill Ian N.
Greff Richard J.
Burns Doane , Swecker, Mathis LLP
MedLogic Global Corporation
Mulcahy Peter D.
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