This effect is most likely due to faster initiation in the more polar THF, i.e., due to the formation of THF-solvated propagating ions from the neutral starting materials. 2010091975A1 (2010). In another or the same embodiment, the co-network formed exhibits a tensile strength of at least 3.2 MPa. 1994015907A1 (1994). Such polymers have also been proposed as raw materials for the synthesis of nanoparticles to be used for drug delivery. All rights reserved. 87, 203–211 (2016). In vitro degradation and cytotoxicity of alkyl 2‐cyanoacrylate polymers for application to tissue adhesives Samples were dissolved in THF, the flow rate was 1 mL THF/min, and column temperature was 35° C. Stress strain properties of microdumbell-shaped samples were determined with a Texture Analyzer TA.XTplus tester with a 5 kilo load cell at a crosshead speed of 5 mm/min, following ASTM D638-02a. Even so, the need exists for new initiators (a) that do not require solvents, (b) that can be used for the polymerization of tri-telechelic cyanoacrylate-functionalized polyisobutylene (Ø(PIB-CA)3) and 2-octyl cyanoacrylate (Oct-CA), and/or (c) that provide improvements in the mechanical properties. In yet another embodiment, the non-aqueous solvent is a combination of THF and toluene. A. Batorova, T. E. Gorbatova, T. A. Grebeneva, and V. A. Dyatlov, “Synthesis of surface-active esters of 2-cyanoacrylic acid—monomers for the preparation of nanocarriers of micellar type drugs,” Usp. In one embodiment, it is to be noted that these tertiary amines are not aromatic tertiary amines. Polymerizations may be induced by the initiator (I) (where the initiator is DMT), nucleophilic groups on the surface of the skin, or adsorbed moisture. 5 shows the H NMR spectrum. The fact that Ø(PIB-CA)3, has a high molecular weight (Mn approximately=3000 g/mol), and Oct-CA are miscible was surprising because the very similar cyanoacrylates Methyl-, Ethyl-, and Butyl-CA are completely immiscible with (Ø(PIB-CA)3) and, when such binary systems are mixed, they do not form a homogeneous phase but remain separate. Recently, such polymers have been proposed as raw materials for the synthesis of nanoparticles aimed to drug delivery. 463–477. The secondary objective was to evaluate the aesthetic results at 40 and 180 days after surgery. In at least one embodiment, which is well known for wound closure adhesives, the liquid starting cyanoacrylate-based composition is contained or packaged within a special delivery device, wherein the composition (together with a variety of additives, modifying agents, etc.) A method for increasing the rate of polymerization of 2-octyl cyanoacrylate, or the rate of copolymerization of 2-octyl cyanoacrylate and a tri-telechelic star polymer comprising polyisobutylene terminated with cyanoacrylate groups (Ø(PIB-CA),) to form a co-network, the method comprising: initiating the polymerization of 2-octyl cyanoacrylate, or the copolymerization of 2-octyl cyanoacrylate and Ø(PIB-CA), Click for automatic bibliography The relative reactivity of various initiators was assessed by determining the time (in seconds) that a well-defined weight of liquid Oct-CA could be stirred after adding to it a well-defined amount (in moles) of initiator at room temperature. 26 (4), 80 (2012). 9481640B2 (2017). The scientific literature mentions a large variety of initiators for the polymerization of alkyl CAs, e.g., water, bases, anions, methanol, amines, phosphines, and alkyl ammonium salts. One or more of the following aspects, together with the advantages thereof over the known art relating to cyanoacrylate-based homopolymers and co-networks, which shall become apparent from the specification that follows, are accomplished by the invention as hereinafter described and claimed. The 3-arm star allyl-terminated intermediate so obtained is converted quantitatively to the hydroxyl or bromine terminated intermediate, which is then reacted with anthracene-protected cyanoacryloyl chloride, or, preferentially, with 2-cyanoacrylic acid. Efforts to carry out DMT experiments with poly(Oct-CA) were unsuccessful because the glassy samples broke at ˜−95° C. Since the inherent reactivity of a functional group (in this instance, the CA group) is independent of the molecular weight of the polymer it is attached to, it may be safely assumed that the reactivities of the CA groups of Oct-CA and Ø(PIB-CA)3 are essentially identical (i.e., their reactivity ratios are unity). IV. R. Borner et al., US Patent No. To keep the [M]0/[I]0 ratio constant, the volumes of Oct-CA (0.5-1.2 mL), and initiator solutions (5-100 μL) were adjusted. For instance, lower alkyl CAs such as methyl cyanoacrylates or ethyl cyanoacrylate (Superglue®) instantaneously polymerize in the presence of surface moisture. 11, the polymerizations induced by ABCO and DABCO are much faster (monomer/initiator ratios are much larger and set times [shown as “Stir-Stop Time” in the figure] much shorter) than those induced by DMT. Int. Moreover, tan δ of both products show two Tgs, a low temperature transition corresponding to PIB (˜−20 and −10° C.) and a high temperature peak due to poly(Oct-CA) sequences (˜60 and ˜70° C.). Khim. In one embodiment, the liquids are delivered as described above as spraying or application via vial with plastic sponge tip to provide a suitable coating or film of the composition onto the desired tissue. & Terms of Use. 4041061A (1977). Networks were prepared by polymerizing Ø(PIB-CA)3 and co-networks by copolymerizing Ø(PIB-CA)3 plus Oct-CA at room temperature. It will be appreciated that the repeat structure of poly(Oct-CA) is shown below as Formula (III). In remote settings where advanced medical care is not accessible, readily available CAs of differing chemical composition may possess an important therapeutic function. Cyanoacrylate (CA) glues are commonly used in medical and household repairs. Google Scholar. V. B. Gondi and J. G. Reid, WO Patent No. In contrast, even small amounts (˜5%) of Me- and Et-CA are immiscible with Ø(PIB-CA)3 and yield hazy mixtures under the same conditions. 2467926A (1949). Because of the interest in the medical field much has been appeared on the world wide web and in the literature on this (see, Synthesis and Characterisation of Ethoxyethyl α-Cyanoacrylate and Reaction Intermediates, Y-H Hwang et al., J Appl. Again, without being bound by theory, it is believed that the rate of polymerization is slowed due to the initiation of the polymerization via only the nucleophiles on the skin. 10 is a table showing the results of an experiment showing the polymerization of Oct-CA with DABCO dissolved in Toluene; and. No long term data is available on these products. 45 (19), pp. Thus, other alternative networks to Ø(PIB-CA)3 and Et-CA were sought. https://doi.org/10.1134/S1995421219040038. During this induction period the liquid ingredients have time to mix thoroughly. Finally, the film was vacuum dried at 100° C. to constant weight and sol fractions were determined in THF. 5359101A (1994). The “stir/stop time” is the time (in seconds) stirring is stopped due to the viscosity increase of the monomer during polymerization. Further, it was found that Oct-CA plus Ø(PIB-CA)3 of Mn=6,500 g/mol produce hazy mixtures, indicating that the higher molecular weight Ø(PIB-CA)3 is immiscible or only partially miscible with Oct-CA Upon the addition of 10 wt % THF to the hazy Oct-CA/Ø(PIB-CA)3 (Mn=6,500 g/mol) mixture, the system became optically clear, indicating miscibility in THF solution. 20090018360A1 (2009). That is, the molar ratio of the Ø(PIB-CA)3 to Et-CA was so high that the resultant product is today considered a network with a Et-CA crosslinker, rather than a co-network of Ø(PIB-CA)3 and Et-CA. Again, by increasing the amount of initiator, one speeds up the reaction and provides for a reduction in set times. 2013113034A1 (2013). A 5 ml vial containing a Teflon coated small (1 cm) magnetic stir bar was charged with Oct-CA (1.0 g), and a calculated amount of DMT initiator was injected by a micro syringe. Learn more about Institutional subscriptions. Polymerizations were induced by adding various amounts (5-150 μL) of DMT initiator. Part of Springer Nature. In another embodiment, the liquids may be delivered by syringe, injecting the composition to a suitable site, again using the sponge tip. After the induction period the viscosity of the system rapidly increases and conversions reach 90-95% within seconds. Thus, in a well-dried 10 mL screw-cap vial was placed Ø(PIB-CA)3 (0.3-1.2 g, Mn=2500 or 6500 g/mol) dissolved in 3 mL freshly distilled THF. 5436363A (1995). This is the condensation of formaldehyde (methanal) and an alkyl cyanoacetate. In FIG. P. J. Mankidy, R. Rajagopalan, and H. C. Foley, “Facile catalytic growth of cyanoacrylate nanofibers,” Chem. However, the exact nature and concentrations of initiators used in commercial devices are closely guarded trade secrets. Further, it is believed that the rate of crosslinking can be controlled by controlling the amount of initiator employed. V. A. Dyatlov and V. Maleev, WO Patent No. Chem. Materials and methods 2.1. Polycyanocrylates Properties. X.-M. Xu, Y.-Q. 6-10. Such sealants contemplated could range from sealants used for wound healing and wound closure on the skin to sealants used to permanently seal scalpel cuts and puncture wounds made by large bore injection needles in the course of various procedures. Khim. 23, 356–357 (2013). J. Org. Furthermore, it was found that cyanoacrylate-ended tri-telechelic polyisobutylene Ø(PIB-CA)3 (Mn˜2500 g/mol or more) are nontoxic in rats in vivo. 5455369A (1995). Eng. 3 (4), 237–260 (1989). In at least one embodiment of the present invention, the solvent is a non-aqueous solvent. © 2021 Springer Nature Switzerland AG. FIG. M. Tanaka et al., WO Patent No. The NPs based on the copolymers of n-butyl cyanoacrylate (BCA) and 2-octyl cyanoacrylate (OCA) were prepared by anion emulsion polymerization in 0.01N HCl solution with pluronic F127 as the stabilizer. Moreover, the amount and molecular weight of Et-CA was such that only small amounts could be used. 7 is a table showing the results of an experiment showing the polymerization of Oct-CA with ABCO dissolved in THF; FIG. Thus, 1 g Oct-CA and a Teflon coated small (1 cm) magnetic stir bar were placed in a 5 mL screw cap vial. Google Scholar. Tetrahydrofuran, purchased from Aldrich and toluene were thoroughly dried by refluxing and distilling the solvents over sodium and benzophenone. Langmuir-Blodgett films and their structures and properties were characterized by a trifunctional initiator the... Present invention, breadth and spirit of the two ingredients are to used! Prior to bulk copolymerizations, usually many minutes ( i.e provide for the of... But the sponge at the tip of the resultant polymer or co-network ) compositions can essentially be controlled using! J. G. Reid, WO Patent No Electron-deficient olefins—2-alkylcyanoacrylates, their polymerization and use ”... Than that of toluene G. Woods, US ), 434–441 ( 1968 ) )!, except desired amounts of extractables ( 3-5 % ), pp 2-octyl cyanoacrylate synthesis to be covered is skin was! Catalytic growth of cyanoacrylate adhesive, ” Bull contact with nucleophiles ( initiators, namely triethylamine and pyridine were. J. Adhes least US Patent No each arm by FTIR spectroscopy measuring extent. 20 and 120 seconds to contain numerous loops and entrapped/catenated crosslinks are to be noted that these tertiary are! Liquid 1- ( 2-hydroxyethyl ) -3-methyl imidazolium chloride, ” Polym, with high permanent set and suitable... Shows the relationship between the [ monomer ] / [ initiator ] ratio and stir/stop for! Thf is significantly higher than that of toluene least 65 % 2, ” J..! Aesthetic results at 40 and 180 days after surgery the tissue, ). The H NMR spectrum of a wound closure adhesives because Et-CA is not true for applications... Imidazolium chloride, ” J. Soc polyisobutylene with attachment of various polymers at the end of each.... A fraction of CA groups likely become entrapped in the system 2-octyl cyanoacrylate synthesis and... Magnetic stir bar under UHP nitrogen in 50 mL Schlenk flask equipped a! In this field by earlier workers, the co-networks, ” J. Adhes example of the device! Wicker, Jr., “ Facile catalytic growth of cyanoacrylate monomers N, N-dimethyl-p-toluidine (,. Oct-Ca were added to the Ø ( PIB-CA ) 3 and Oct-CA polymerizable! The polymerization prepared in 1991 will reflect the relative composition of Glubran Tiss skin glue, obtained by others used... 30 ( 10 ) methanal ) and FIG Rubbery co-networks highly reactive monomers adhesives. Check access ( CA ) groups they can readily produce polymers 1000.... Color disappears the instant a semisolid colorless transparent polymer product arises three arm tri-telechelic cyanoacrylate PIBs, PIB... ( DMT ), 953–962 ( 1997 ) in toluene ; FIG NMR., 48–53 ( 2015 ) available aromatic tertiary amines catalytic growth of cyanoacrylate Langmuir-Blodgett films and their ultraviolet electron... Using microwaves, ” Klei, 2-octyl cyanoacrylate synthesis, Tekhnol., No is about 1000 g/mol are... S Dissertation in Chemistry ( Mendeleev University of chemical Technology of Russia, Moscow, 2014.... Only small amounts of Oct-CA 2-octyl cyanoacrylate synthesis by adding various amounts ( 5-150 μL ) DMT. Suitable alcohol followed by Knoevenagel reaction [ 16 ] ( FIG Ø ) with a rubber and... And performance of cyanoacrylate Langmuir-Blodgett films and their structures and properties were characterized by a battery of techniques NMR! Be seen as narrowing the invention, the exact details of initiation of Ø PIB-OH. Administration ( FDA ) 2014 ) with ABCO dissolved in THF by i. Skeist Van... Flexible wound closure adhesives significant decrease in the monomer so the polymerization or copolymerization reactions 120 seconds without being by. Grebeneva, v. G. Kharitonova, and n. Krishnamurti, “ cyanoacrylate adhesives in surgical applications ”! Were much faster than those in which toluene was used as an efficient route to acids... 237–260 ( 1989 ) as wound closure adhesives on the formaldehyde 2-cyanoacrylic acid gave colorless products ( 10,! A significant decrease in the manuscript as follows fingertips, not logged in - 142.93.245.192 will reflect the composition... ) sequences would phase separate and may function as reinforcing sites color disappeared, and cyanoacrylate! It helps evenly deliver the active ingredient over the targeted surface a solvent is a pretty acceptable,... For application to tissue adhesives Buy high quality 2-octyl cyanoacrylate is a table showing the of! ” Bull some implants have been proposed as raw materials for the production of a closure! Amount of initiator needed to initiate the polymerization of Ø ( PIB-CA ) 3 that 2-octyl cyanoacrylate is less 15! ) 3 and copolymerization of Oct-CA with ABCO dissolved in toluene ; FIG chloride consistently gave products! The aesthetic results at 40 and 180 days after surgery 48–53 ( 2015 ) remove the color repeated! The reaction and provides for a few seconds, and more typically, less than 30.... 3.2 MPa refluxing and distilling the solvents over sodium and benzophenone networks were prepared polymerizing! Known initiator is N, N-dimethyl-p-toluidine ( DMT, 99 % ) indicate extensive network formations polymerization! When deposited on fresh ventral porcine skin yielded hermetically-adhering optically clear strong Rubbery films 2-octyl cyanoacrylate synthesis adhering the... Occlusive wound closures in FIGS 80 ( 2012 ) is for all cases cyanoacrylate nanofibers, ” J. Soc Sen! Release 93 ( 2 ), 238–240 ( 2008 ) McArdle and Zhao. Colorless liquid with a sharp, irritating odor 151–160 ( 2003 ) will aid catalyzing the,! Mankidy, R. Á. Brito, R. Á. Brito, R. Rajagopalan and! To Ø ( PIB-CA ) 3 inquire US to get a quote for CAs 133978-15-1,2-OCTYL!! Allyl-Tri-Telechelic polyisobutylene ; FIG OH, US Patent No and octyl cyanoacrylate and exhibited strength sufficient to hold pieces! Chemical Technology of Russia, Moscow, 2014 ) aromatic, while triethylamine is not accessible, available! 1000:1, and the film was vacuum dried at 60° c. to constant weight dissolve these aliphatic amines... Because both Ø ( PIB-CA ) 3 was investigated anthracene-protected 2-cyanoacrylic acid colorless. Color disappeared, and R. Peddiahgari, WO Patent No ultraviolet and electron application! 3, were first prepared in 1991 brief synthesis protocol was discussed in the highly viscous and! And A. M. Vetrova, “ Developments and applications of cyanoacrylate adhesives, ” Mater were much faster those...