Liquid Cyanoacrylates

These acids can be used alone or as mixtures. It is especially advantageous to use a mixture of liquid and gaseous acids. The gaseous acid will stabilize free monomer in the headspace of a container, while the liquid acid will prevent premature polymerization of the bulk monomer or adhesive. However, it is important to use only a minimum amount of acid, because excess acid will slow initiation and the formation of a strong adhesive bond. It can also accelerate the hydrolysis of the alkyl cyanoacrylate monomer to 2-cyanoacrylic acid, which inhibits the polymerization of the monomer and reduces molecular weight of the adhesive polymer. While carboxylic acids inhibit the polymerization of cyanoacrylate monomer, they do not prevent it completely [15]. Therefore, they cannot be utilized as stabilizers, but are used more for modifying the reactivity of instant adhesives. 

All of the eommereial alkyl eyanoaerylate monomers are low-viseosity liquids, and for some applications this can be an advantage. However, there are instances where a viseous liquid or a gel adhesive would be preferred, sueh as for application to a vertical surface or on porous substrates. A variety of viscosity control agents, depending upon the desired properties, have been added to increase the viscosity of instant adhesives [21]. The materials, which have been utilized, include polymethyl methacrylate, hydrophobic silica, hydrophobic alumina, treated quartz, polyethyl cyanoacrylate, cellulose esters, polycarbonates, and carbon black. For example, the addition of 5-10% of amorphous, non-crystalline, fumed silica to ethyl cyanoacrylate changes the monomer viscosity from a 2-cps liquid to a gelled material [22]. Because of the sensitivity of cyanoacrylate esters to basic materials, some additives require treatment with an acid to prevent premature gelation of the product. 

Despite the universal use of sutures for wound closure, there is a need to utilize adhesives instead, because of their ease of use and the reduced risk of infection. Alkyl cyanoacrylate adhesives have been studied extensively for this use, and a significant amount of research has been performed to evaluate their interaction with living tissue [40,41 J. They have been approved for external use only, because of concerns with the fact that the polymers do not readily biodegrade and can cause inflammation around the area to which it was applied. However, these concerns are reduced for -butyl cyanoacrylate, as compared to the ethyl cyanoacrylate. There is even some evidence that their use as liquid sutures actually reduces the rate of infection around the healing wound or surgical incision [42J. 

Humans have developed strong skin reactions when rechallenged with the liquid. Allergic contact dermatitis has been reported in workers handling methacrylate sealants, including methyl methacrylate. In another report, five subjects were shown by bronchial provocation tests to have occupational asthma due to methyl methacrylate or cyanoacrylates. ... 

Ihe polymers of the 2-cyanoacrylic esters, more commonly known as the alkyl 2-cyanoacrylates, are hard glassy resins that exhibit excellent adhesion to a wide variety of materials. The polymers are spontaneously formed when their liquid precursors or monomers are placed between two closely fitting surfaces. Tile spontaneous polymerization of these very reactive liquids and the excellent adhesion properties of the cured resins combine to make these compounds a unique class of single-component, ambient-temperature-curing adhesive of great versatility (Table 3). The materials that can be bonded run the gamut from metals, plastics, most elastomers, fabrics, and woods to many ceramics. 

Both the liquid and cured 2-cyanoacrylic esters support combustion. 

Polycyanocrylate - 2-Octyl-cyanoacrylate plasticized and self-stabilized is the slower, but slightly more flexible (octyl- vs. ethyl-substituent group) ionically curing adhesive that is catalyzed by weak bases including water. The liquid and nonsolvated DermabondR product forms a continuous film in -3-5 min that is continuous and very adherent to tissue. 

Formulations of 2-octyl cyanoacrylate (Liquid Bandage12), polyvinyl acetate, poly-butryal were successful in rat studies, however, a spray-on bandage is recommended for ease-of-use and, especially for one-hand application such as with a pump-type spray bottle. Aerosol cans are under pressure and may not be allowed to be carried on aircraft. 

Both, the liquid and cured 2-cyanoacrylic esters support combustion. These adhesives should not be used near sparks, heat, or open flame, or in areas of acute fire hazard. Highly exothermic polymerization can occur from direct addition of catalytic substances such as water, alcohols, and bases such as amines, ammonia, or caustics, or from contamination with any of the available surface activator solutions. 

One of the most striking differences between protein-dominated substrates e,g., skin, tissue masses, and blood) and other solid, semi-solid, or liquid surfaces is in their wettability and adhesiveness with other materials. Work on the development of surgical adhesives based upon the poly(a-cyanoacrylates) used successfully in hemostasis for massive... 

Tissue adhesives are formulated from cyanoacrylate compounds such as bucrylate, enbucrilate, or mecry-late which polymerize in an exothermic reaction on contact with a fluid or basic substance to form a strong, flexible, and waterproof bond. They are synthesized by reacting formaldehyde with alkyl cyanoacetate to obtain a prepolymer, which may be depolarized to a liquid monomer by heat. This monomer may then be modified by altering the alkoxycarbonyl (-COOR) group of the molecule to give compounds of different chain lengths. 

Most cyanoacrylate adhesives are maintained in a liquid state at room temperature by the addition of free radical and anionic stabilisers at suitable concentrations so as not to interfere with the functionality of the adhesive. These stabilisers/inhibitors are added at... 

The physical properties of the monomers must be discussed along with those of the cured polymers because consideration of one without the other presents an incomplete picture. The 2-cyanoacrylic ester monomers are all thin, water-dear liquids with viscosities of 1 3 mPa-s(=cP). Although a number of the esters have been prepared and characterized, only a relative few are of any significant commercial interest, and, of those, the methyl and ethyl esters by far predominate. The physical properties of the principal monomers are induded in Table 1. 

Cyanoacrylates are still used in a variety of medical applications to close wounds and to protect wounds from infection. The 2-octyl ester is used for this purpose because it has fewer hazardous side effects than do the methyl and ethyl esters. Cyanoacrylate is preferred to stitches for closing wounds because it is less likely to become infected and tends to leave fewer scars. For this reason, the compound is often used for cuts on the face, although it cannot be used in the nose or mouth. Consumers can buy cyanoacrylate products such as BandAid brand Liquid Bandage for home use. 

Emulsions of polyvinyl acetate and polyalkyl acrylates have been used as tub caulking compositions, spackling compounds and as building sealants.22 Acrylic sealants which harden in the presence of powdered iron or copper meet Federal Specifications TT-S-00230C. 27 Liquid monomers, such as polyethylene glycol dimethacrylate and butyl alpha—cyanoacrylate have been used as room temperature curing sealants.22 22. 

In response to these concerns, and particularly the ones associated with tire nonabsorbable cyanoacrylates that are used clinically. Linden and Shalaby disclosed a novel, absorbable tissue adhesive composition that addressed, to a practical extent, the drawbacks of the absorbable bioadhesive as well as nonabsorbable cyanoacrylates. In effect, these absorbable tissue adhesive compositions were based (1) primarily on methoxyalkyl cyanoacrylates and preferably methoxypropyl cyanoacrylate as the precursor of an absorbable tissue adhesive polymer and (2) on a polymeric, highly absorbable, liquid comprising an oxalate ester of triethylene glycol as a modifier to modulate the viscosity of the overall composition, lower the heat of polymerization, and increase the compliance and absorption rate of the cured adhesive joint. In a more recent disclosure by Shalaby, a number of other useful modifiers were described and the functional performance of the new adhesive compositions was reported. ... 

An absorbable polymeric modifier that is compatible with the chosen cyanoacrylate to achieve a moderate-to-high preuse viscosity for ease of application, and to increase the absorption rate and compliance of tile cured adhesive for minimizing residence time at the application site and maximizing mechanical biocompatibility — for this, highly absorbable liquid oxalate polymers, such as poly(triox-yethylene oxalate) (PTOEO) and amorphous or low-melting absorbable copolyesters such as those described in Chapter 3 — polyaxial copolyesters and other copolymers based on cyclic monomers — were selected. 

Cyanoacrylate adhesives can be defined as single-component chemically active liquids that react very rapidly with moisture or other weakly alkahne materials to form clear, hard solids. Their important characteristics are ... 

With cyanoacrylate adhesives, the reactor used to convert the liquid monomer to the hard solid is the space between the parts being bonded. When conditions vary in this space, the performance of the adhesive will vary. Such parameters as temperature, humidity, space between the parts, and the type of surface being bonded can vary considerably in a given application. 

Harris et al ° were the first to describe the use of interfacial polymerization of poly[n-butyl-2-cyanoacrylate] (PBCA) to prepare gas-filled CA. PBCA has also been described for UCA by Schmidt and Roessling. The wall of the final agent is formed by collection of PBCA nanocapsules around a surfactant-stabilized template, and the liquid core is... 

The most commonly used liquid tissue adhesives are cyanoacrylates. Their low viscosity makes their delivery easy through small coaxial microcatheters. However, their rapid polymerization when in contact with blood, can make precise and safe occlusion challenging. Usually they are mixed with an oil-based contrast media, such as Ethiodol (Savage Laboratories, Melville, NY). The contrast serves to both opacify the cyanoacrylate and slows the polymerization time [30]. 

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