CA1175760A - Female sterilization employing methyl cyanoacrylate - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
The present invention provides an ampule for storing MCA and similar compositions comprising: a container body composed of polytetrafluoroethylene defining a cylindrical chamber for holding the composition to be stored; a slidable sealing piston member composed of a block polymer of polytetra-fluoroethylene and polyethylene positioned at one end of the chamber, the piston having a peripheral ring seat; an "O" ring fitted in the peripheral seat and in compressive relationship with the inner wall of the chamber, and a diaphragm stopper sealing the other end of the chamber. The invention also provides an ampule defining a storage chamber for an MCA ster-lization composition, the chamber including a quantity of de-oxygenated nitrogen.

Description

~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 7~i~

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.

Claims (4)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. 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 polyethylene 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 relationship with the inner wall of the chamber, and a dia-phragm stopper sealing the other end of the chamber.

2. An ampule defining a storage chamber for an MCA
sterilization composition, the chamber including a quantity of deoxygenated nitrogen.

3. The ampule of claim 2, wherein the oxygen level of the nitrogen is less than about 0.5 ppm.

4. The ampule of claim 1, wherein the "O" ring and the diaphragm are coated with polytetrafluorethylene.