Note: Descriptions are shown in the official language in which they were submitted.
~L'7576~
This invention relates to an improved methyl cycano-
acrylate composition for use in female sterilization. The
improved composition provides improved inhibition and long-
term storage, i.e., longer "shelf-life" or monomeric methyl
cyanoacrylate. It also provides enhanced sterilization results.
The present invention in particular provides an ampoule
for stray methyl cyanoacrylate and similar compositions.
This application is a divisional application of
co-pending application No. 365,875 filed December 1, 1980.
Methyl cyanoacrylate (MCA) is a well known chemical
product that has found application in the field of permanent
sterilization of human females. Sterilization is accomplished
by the introduction of small quantities of MCA into the
fallopian tubes. Its contact there with body moisture poly-
merizes the MCA and blocks the fallopian tubes. With the
passage of time, fibrous tissue growth replaces the MCA and
permanent sterilization results. This use and procedure is
described in the U.S. Patent Nos. 3,822,702 and 3,948,2~9.
The property of polymerization which makes MCA useful
in female sterilizati-on also makes it difficult to store i.e.,
it has a short "shelf-life". MCA polymerizes under a variety
of conditions including exposure to even trace amounts of mois-
ture, oxygen, heat, high energy radiation, and exposure to
active organic sites. Consequently, it is difficult to store
MCA for any period of time due to its tendency to autocatalyze
itself into a solid cured polymer during storage.
It is known that one can add quantities of polymeri-
zation inhibitor to MCA to reduce the tendency to autocatalyze
itself during storage. For example, acetic acid, sulfur dioxide,
phosphoric acid and hydroquinone have all been used individually
as separate inhibitors for MCA and can provide a "shelf-life"
up to five or six years. Unfortunately, to obtain long "shelf-
s~
life" requires the use of such large amounts of inhibitor thatthe sterilization action of the MCA is -drastically and detri-
mentally affected. Thus, in the prior art, each of the fore-
going inhibitors has been used individually in relatively low
amounts to provide inhibited MCA having a "shelf-life" on the
order of three or four months. Even then, the sterilization
results are less than is desirable.
In general, the use of these various separate inhibi-
tors, as practiced in the prior art, has tended to decrease
the number of successfu] sterilizations i.e., those in which
there is complete closure of the fallopian tubes and permanent
sterilization, as compared to the use of uninhibited MCA,
without providing a satisfactory "shelf-life" of the MCA.
For example, when phosphoric acid inhibitor is used, "closures"
resulted at best in only about 58~ of the test results and the
maximum "shelf-life" was about four months. On the other hand,
with the improved composition of this inven~ion, not only is
the "shelf-life" of the MCA improved to as long as six months
to over a year, but successful sterilization results are provided
which are comparable to those obtained when uninhibited MCA
is used, i.e., in close to 100% of the-test cases.
Another separate problem which has detrimentally
affected the "shelf-life" of MCA has been found to exist in the
ampule containers used therefor. In accordancP with this
invention, improved ampules of gas impermeable materials are
provided and a nitrogen bubble is included therein which is
substantially oxygen free.
In copending application No. 365,875 there is dis-
closed and claimed a new inhibited MCA composition including
amounts of an acid, sulfur dioxide and either hydroquinone,
hydroquinone monomethyl ether or butylated hydroxyanisole
tBHA). The constituents are preferably used in a very pure form
~1~757i&~
e.g., 99.9% pure or better where possible. The present invention
provides an improved ampule container arrangement for MCA.
According to one aspect of the present invention
therefore there is provided an ampule for storing MCA and
similar compositions comprising: a container body composed of
polytetrafluorethylene defining a cylindrical chamber for holding
the composition to be'stored; a slidable sealing piston member
composed of a block 'polymer of polytetrafluorethylene and poly-
ethylene positioned at one end of the chamber, the piston having
a peripheral ring seat; an "O" ring fitted in the peripheral
seat and in compres'sive rel'ationship with the inner wall of
the chamber, and a diaphragm stopper sealing the other end of
the chamber.
According to another aspect of the present invention
there is provided an ampule'defining a storage chamber for an
MCA sterilization composition, the chamber including a quantity
of deoxygenatedlnitrogen.
The present invention will be described with reference
to the accompanying drawings in which:
Figure l is a perspective view of an embodiment of an
ampule according to the invention;
Figure'2 is a cross-sectional view of the ampule
shown in Figure 'l taken along line 2-2 of Figure l; and
Figure 3 is a perspective view of the piston stopper
utilized in the 'amp'ule shown in Figures l and 2.
The MCA referred to herein, methyl-2-cyanoacrylate,
may be~any of the commercial forms thereof in which the
supplier!s inhibitors have been substantially removed i.e.,
to a purity level of at least about 99.9%. "Eastman 910"
(a trade mark~ is an example of the most readily ayailable
commercial form. It may be obtained from Eastman Chemical
products, Inc., ~ox 431, Kingsport, Tennessee 37662.
~L75~0
Commercially added inhibitors e.g., hydroquinone,
phosphoric acid and phosphoric anhydride may be readily separated
by distilling the MCA away from the inhibitors under reduced
pressure to remove the MCA as the distillate. This should
be repeatedly carried out to obtain a high purity MCA, e.g.,
one on the order of 99.9% or higher.
Preferably, the MCA will be prepared especially for
use in the invention without inhibitors so as to provide high
purity material. The'preparation of MCA is known to those
familar with the'chemical arts and need not be described in
detail herein. Generally, it is prepared by pyrolyzing the
polytalkyl)-2-cyanoacrylates produced when formaldehyde is
condensed with the corresponding alkyl cyanoacetates. Detailed
information is available in U.5. Patent 2,763,677 entitled
"Process for Making Monomeric Alfa-cyanoacrylates", issued
in 1956.
To the substantially inhibitor-free and preferably
high purity MCA, an organic carboxylic (containing -COOH group)
acid is added ranging in amount from about 12,500 ppm to
about 60,000 ppm, about 15,000 ppm + about 100 being preferred.
The term "ppm" is used herei'n throughout
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7~i~
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on a mole/mole basis.
Glacial acetic acid is the preferred acid although
other organic carboxylic acids, not ~arm~ul to ~ody tissue,
such as propionic acid, ~utyric acid or benzoic acid and
many o~er organic carboxylic acids may he used. Eowever,
pxefera~ly suc~ ac;ds will ~e of ~gh purity eg., 99.9%
or ~etter.
Sul~ur dioxi~de CS021 is also adde~ to the MCA ranging
in amounts from about 500 ppm to a~out 150a ppm, a~out
750 ppm + a~out 250 ~eing preferred. Satisfactory, mois-
ture free, hig~ purity S02 is commercially availa~le from
many suppliers. It is dried ~y the supplier ~y passing it
through a drying tower and is availa~le 99.9% pur~.
Hydroqu;none, hydro~uînone monomethyl ether or buty~
lated hydroxyanisole (BHA) ar~ also added to the MCA either
;ndiviaually or as a mixture of any two or three thereof.
This component of the new composition provided herein may
range in a~ount from about 50 ppm to a~out 250 ppm, a~out
100 ppm + about 10 being preferred. Hydroquinone is the
preferred component. These components are all commercially
available in recrystallized form at purity levels of 99.9%
or higher.
The relative a~ounts of the additives specified above
for the MCA composition may be varied within the substan-
tial range specified, as desired. That is, when one or moreof the additives are increased in amount it is not necessary
to decrease the r~lative ~mounts of other additives. Any
combination of relative amounts within the specified ranges
will provide the improvements of the invention as described
herein. Any departure from these ranges will drastically
and detrimentally affect the results obtained i.e., "shelf-
life" and sterilizat~on effectiveness.
EXAMPLE
Acetic Acid - 15,000 ppm + 100 ppm - 99.9~ purity
Sulfur dioxide 750 ppm -~ 250 ppm - 99.9% purity
Hydroquinone - 100 ppm + 10 ppm - 99.9% purity
Ba~ance MCA - 99.9~ purity
st~
Closure was observed in better than 90% of the test
cases utilizing the above example composition.
Referring to Pigures 1 - 3, the ContainerS in which
MCA s~erilizat;on composit;ons 10 are stored take the form
of a sealed ampule compr;sing a cyl;ndrical tube 12, pre-
ferahly of polytetrafluorethylene (PTFE~ sealed at one
end 14 by a stopper or diaphragm 16 of ru~er or the li~e
which has been spray coated with PTFE 17. At the other
end 18 is a closure member, preferably in the fQrm of
1~ mo~le piston 20 molded from Tefzel a trade mark of D~nt de
Nemours Co. of Wilington, Delaware. T~is material is a
~lock polymer of polytetrafluorethylene and polyethylene.
For sealing the other end of the ampule and for moving
toward the diaphragm stopper 16 to force the MCA composi-
tion 10 from the ampule cnamber 22 which is formed between
the two ends thereof. This i5 accomplished by inserting
the needle of a hypoaermic syringe through the diaphragm
stopper. The piston is then moved to force the material
thru the needle out of the container.
Piston stopper 20 carries an "O" ring 24 fitted in a
seat 26 on the piston. Piston 20 may take a variety of
shapes, one of which is shown in the drawing for providing
effective sealing in cooperation with the inner diameter
of the cylinder 12. Preferably, the materials of the "O"
ring will be a high modulus rub~er such as butyl, natural,bum~, neoprene rubber and the l;ke. Simllar materials will
be used for diaphragm member 16. The "O" ring and inner
diameter of cylinder 12 will be relatively sized so as to
provide a compression seal there~etween. To render the O"
ring i~pervious to the c-ntrance of oxygen into the ampule
or the loss of sulfur dio~ide therefrom, it wlll be spray
coated with polytetrafluorethylene as is the diaphragm 16.
Several spray~d coats of polytetrafluorethylene, preferably
four arc ~scd. Four sprayed coats will ordinarily proviae
a coating of ~bout 1 mil thickness, which is satisfactory.
Container end 14 insludes a neck portion 28 to facili-
tate thc ~r~ss ~itting of a metal cap 30 thereto for the
~1~57~
purpose of holding diaphragm 16 in place and sealed to cylinder
12 as shown.
The various plastic parts of the container are molded
to tolerances of about ~ 1 mil of the desired size and are press
fit together.
As additional protection for the stability of the
MCA composition in the ampule, a nitrogen bubble 32, containing
less than 0.5 ppm oxygen is included in the ampule.
Nitrogen of this guaranteed purity level is commer-
cially available from many suppliers. The container isassembled and filled in a 0.5 ppm oxygen-free nitrogen
environment. Consequently~ the nitrogen bubble is readily
formed in the container. The presence of this bubble
protects the MCA from exposure to oxygen which detrimentally
affects MCA.
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