Upload
truongbao
View
219
Download
2
Embed Size (px)
Citation preview
Wound Adhesive from Cyanoacrylate: Synthesis and
Characterization
Rajangam Vinodh1, Cadiam Mohan Babu
1, Aziz Abidov
1,
Rramaswamy Ravikumar1, Muthiahpillai Palanichamy
1, Eun Young Choi
2
and Hyun Tae Jang1*
1 Department of Chemical Engineering, Hanseo University, Seosan 360-706, South Korea
2Department of Cosmetology, Hanseo University, Seosan 360-706, South Korea
Abstract. 1-octyl cyanoacryalte is a main component of medical cyanoacrylate
glues. As it rapidly polymerizes with water as an initiator, there are practical
difficulties in designing simple synthetic routes. Any synthetic routes that
evolve free nucleophilic products cannot, therefore be successful. Its synthesis
too has not been reported in the open literature so far. Synthetic methods, which
involve esterification of cyanoacetic acid with a chosen alcohol, polymerization
by knoevenagel condensation and subsequent depolymerization, are applied to
the synthesis of lower membered alkyl cyanoacryaltes in which the alkyl groups
carry less than 8 carbons. We have synthesized 1-octyl cyanoacetate by a usual
method involving p-toluene sulphonic acid as the catalyst. Its conversion to
poly (1-octyl cyanoacrylate) is effected with 1, 3, 5-trioxane in a solvent free
route, although paraformaldehyde has been suggested in few patents. Its FTIR
spectrum confirmed its functional groups: Its –OH stretching yielded a broad
band around 3400 cm-1. Its depolymerization to high yield of 1-octyl cyano
acrylate is under progress: during depolymerization p-toluene sulphonic acid,
hydroquinone and phosphorous pentoxide are tried. We have avoided high
temperature pyrolysis, as it is verified to degrade long alkyl chain.
Keywords: 1-octyl cyanoacrylate; Wound adhesive; Medical glue; p-toluene
sulphonic acid
1 Introduction
Presently, wound closure techniques have evolved from the earliest development of suturing
materials to resources that include synthetic absorbable sutures, staples, tapes, and adhesive
compounds. The creation of natural glues, surgical staples and tapes to substitute sutures has
supplemented the armamentarium of wound closure techniques. The use of tissue adhesives
has long appealed to surgeons and they have been extensively studied for nearly four decades
for diverse applications including tissue adhesion, wound closure, hemostasis, and closure of
cerebrospinal fluid (CSF) leaks, vascular embolization and application of skin grafts [1].
The ideal method of laceration and incision closure should be simple, safe, rapid,
inexpensive, painless, bactericidal, and result in optimal cosmetic appearance of the scar. The
cyanoacrylate tissue adhesives offer many of these characteristics. Developed in 1949, the
cyanoacrylate adhesives are applied topically to the outermost skin layer. The cyanoacryaltes
Advanced Science and Technology Letters Vol.121 (AST 2016), pp.434-439
http://dx.doi.org/10.14257/astl.2016.121.79
ISSN: 2287-1233 ASTL Copyright © 2016 SERSC
are supplied as monomers in a liquid form. On contact with tissue anions, they polymerize
forming a strong bond that holds the apposed wound edges together. The cyanoacrylate
adhesives usually slough off with wound re-epithelialization within 5–10 days and do not
require removal.
The use of cyanoacrylates has increased significantly in recent years owing to their unique
combination of chemical and physical properties, namely: (1) they cure rapidly at room
temperature; (2) they form strong bonds with a wide variety of different materials without the
addition of a catalyst; (3) they can be easily and safely applied either manually or by automatic
equipment; and (4) they are ready to use without mixing or using a primer [2]. These unique
materials were discovered in 1951 in the course of applied research directed towards the
characterization of stronger, tougher and more heat-resistant acrylate polymers for jet plane
canopies [3].
Sutures have conventionally been the method of approximating wound edges due to their
high tensile strength and favorable cosmetic outcomes. Sutures do, however, have some
downfalls in that they require increased time and a skilled individual to accomplish good
cosmetic outcomes. Over the past four decades, advances have seen other forms of wound
closure methods emerge that address some of the disadvantages of sutures [4-10].
2 Experimental
2.1 Materials
1-octyl cyanoacrylate, cyano acetic acid and P-toluene sulphonic acid were purchased from
Sigma Aldrich, USA. All the other chemicals and solvents bought from Daejung Chemical,
South Korea.
2.2 Preparation of 1-octyl cyanoacrylate
It involves three stages, (i) Preparation of 1-octyl cyano acetate; (ii) Preparation of poly (1-octyl
cyano acrylate) and (iii) Preparation of 1-octyl cyano acrylate.
2.3 Synthesis of 1-octyl cyano acetate
8 g cyano acetic acid, 13 g 1-octanol, 1.0 g p-toluene sulphonic acid and 50 mL toluene were
taken in a 100mL RB flask. It is attached to a Dean-stark trap which in turn attached to a water
condenser. The contents of the flask were heated to 130 C under stirring for 12 h. Water
formed in this esterification was removed by forming azeotrope with toluene in order to
complete esterification. The total amount of water collected in the trap was equal to 3 g. The
round bottom flask was cooled and toluene in it vacuum evaporated. The light red liquid in
the flask was transferred to a 250 mL separating funnel. The trace of residual cyano acetic acid
and p-toluene sulphonic acid were removed by extraction with 20 mL portions of saturated
sodium bicarbonate solution two times. The liquid was then finally washed with 20 mL portions
of water two times, and the liquid transferred to a clean 100 mL beaker. 2 g of anhydrous
magnesium sulphate was added to it, shaken well and allowed to stand for 5h. Then the clear
liquid was transferred to a 100 mL round bottom flask and vacuum evaporated.
Advanced Science and Technology Letters Vol.121 (AST 2016)
Copyright © 2016 SERSC 435
2.4 Synthesis of poly (1-octyl cyano acrylate)
4 g of 1-octyl cyano acrylate was taken in a 100 mL round bottom flask. 1.4 g of para
formaldehyde, 1.0 g of magnesium acetate and 3 mL acetic acid were added to it. The flask was
attached to a reflux condenser and the contents were vigorously stirred at 90 C for 24 h. On
cooling the flask a thick gel of poly (1-octyl cyano acryalte) was obtained. 20 mL ethyl acetate
was added to the flask to dissolve poly (1-octyl cyano acryalte). The solution was transferred to
a 250 mL separating funnel. Its acetic acid is removed by extraction with 20 mL portions of
saturated sodium bicarbonate solution. Then the ester layer was washed 2 times with 20 mL
portion of water. The ester layer was transferred to a 100 mL beaker, and 4g of anhydrous
magnesium sulphate added to it, shaken well and allowed to stand for 5 h. The clear liquid was
then transferred to a clean, dry RB flask and vacuum evaporated. The viscous liquid that
remained in the flask was transferred to a bottle and FTIR analyzed. The schematic
representation of wound healing illustrated in figure 1.
Adhesive
Cyanoacrylate glue container
Fig. 1. Schematic illustration of synthesized adhesive to cure skin wound healing
3 Results and Discussion
3.1 Fourier Transform Infra Red Spectroscopy
Figure 2 shows the FTIR spectrum of 1-octyl cyanoacetate obtained by the reaction of 1-
octanol and cyanoacetic acid. The alkyl –CH2- stretching vibrations yielded intense peaks at
2929 and 2857 cm-1. The –CN stretching occurred at 2265 cm-1. The intense sharp peak at 1749
cm-1 is due to C=O stretch. The –CH2- bending vibrations showed peaks at 1395 and 1467 cm-
1.The group of peaks at 1335, 1266 and 1187 cm-1 are due to ester –COO- vibrations. The peak
at 1007 cm-1 is due to –O-C vibration. The –CH2- wagging occurred at 724 cm-1.
Advanced Science and Technology Letters Vol.121 (AST 2016)
436 Copyright © 2016 SERSC
53
6.7
15
82
.65
72
4.4
0
93
4.2
0
10
07
.85
11
88
.11
12
66
.74
13
36
.02
13
95
.59
14
67
.28
17
50
.81
22
65
.50
28
57
.80
29
29
.54
34
84
.53
-0
10
20
30
40
50
60
70
80
90
100%
T
500 1000 1500 2000 2500 3000 3500 4000
Wavenumbers (cm-1)
Wave number (cm-1)
% T
ran
smit
tan
ce
Fig. 2. FTIR spectrum of 1-octyl cyanoacetate
3.2 Thermogravimetric Analysis
Fig. 3. TGA of 1-octyl cyanoacrylate
Advanced Science and Technology Letters Vol.121 (AST 2016)
Copyright © 2016 SERSC 437
The results of TGA of poly (1-octyl cyanoacrylate) are illustrated in Fig. 3. The thermogram
showed absence of weight loss below 150 C illustrating absence of any entrapped solvent. The
weight loss between 150 and 225 C is assigned to residual 1-octyl cyanoacetate. The steady
weight loss between 225 and 300 C is due to degradation of the polymer into monomer. As the
decomposition occurred in one stage without leaving any residue, the decomposition evidently
rejects random degradation. The polymer is proved to be formed by addition rather than
condensation. The present thermogram depicts the same features as that obtained by piperidine.
Hence, both the polymers are verified to be formed by addition, though their molecular weights
are different. Piperidine is miscible with 1-octyl cyanoacetate; formation of 1-octyl
cyanoacrylate might be more rapid than its polymerization. It accounts for formation of high
molecular weight polymer with piperidine. In contrast potassium carbonate is immiscible with
1-octyl cyanoacetate, so the rate of formation of polymer sight be lower than the rate of
formation of 1-octyl cyanoacrylate.
4 Conclusions
1-Octanol and 2-cyanoacetic acid were esterified in the presence of p-toluene sulphonic acid to
form 1-octyl-2-cyanoacetate. The ester was subjected to the Knoevenagel condensation with
formaldehyde to form poly(1-octyl-2-cyanoacetate) using potassium carbonate or piperidine as
initiators. The polymer was depolymerized using poly phosphoric acid catalyst under vacuum
to obtain the monomer. A simple method of obtaining monomer was also attempted by the
reaction of 1-octyl- 2-cyano acetate and diiodomethane in the presence of potassium carbonate.
This process directly yields the monomer. The second method looks better than the others, and
it can be applied to any type of alcohols.
Acknowledgments. This research was supported by the Korea Association of University
Research Institute and Industry program funded by the Small and medium Business
Administration (C0330026, 2015).
References
1. Shivamurthy, D.M., Singh, S., Reddu, S.: Comparison of octyl-2-cycnoacrylate and
conventional sutures in facial skin closure. Nat. J. Maxillofacial Surgery. 1(1), 15--19
(2010)
2. Shantha, K.L., Thennarasu, S., Krishnamurti, N.: Developments and applications of
cyanoacrylate adhesives. J. Adhesive Sci. Technol. 3(4), 237--260 (1989)
3. Coover, H.W.: J. Coat. Technol. 55, 59 (1983)
4. Chen, K., Klapper, A.S., Voige, H., Del Priore, G.: A randomized, controlled study
comparing two standardized closure methods of laproscopic port sites. J. Society of
Laparoendoscopic Surgeons. 14, 391--394 (2010)
5. Singer, A.D., Fananapazir, G., Maufa, F., Narra, S., Ascher, S.: Pulmonary embolism
following 2-octyl-cyanoacrylate/lipiodol injection for obliteration of gastric varices: an
imaging perspective. J. Radiology Case Reports. 6(2), 17--22 (2012)
6. Ridgway, D.M., Mahmood, F., Moore, L., Bramley, D., Moore, P.J.: A blinded,
randomized, controlled trial of stapled versus tissue glue closure of neck surgery incisions.
Annals of the Royal College of Surgeons of England. 89, 242--246 (2007)
Advanced Science and Technology Letters Vol.121 (AST 2016)
438 Copyright © 2016 SERSC
7. Wachter, D., Bruckel, A., Stein, M., Oertel, M.F., Christophis, P., Boker, D.K.: 2-Octyl-
cyanoacrylate for wound closure in surgical and lumbar surgery. Neurosurgical Review.
33, 483--489 (2010)
8. Mehdizadeh, M., Yang, J.: Design strategies and applications of tissue bioadhesives.
Macromolecular Bioscience. 13(3), 271--278 (2013)
9. Shivamurthy, D.M., Singh, S., Reddy, S.: Comparison of octyl-2- cyanoacrylate and
conventional sutures in facial skin closure. National J. Maxillofacial Surgery. 1(1), 15--19
(2010)
10. Durai, R., CH Ng, P.: Easy way of gluing the skin of surgical wounds. International J.
Clinical Practice. 63(7), 1115--1117 (2009)
Advanced Science and Technology Letters Vol.121 (AST 2016)
Copyright © 2016 SERSC 439