U.S. patent number 3,867,329 [Application Number 05/283,840] was granted by the patent office on 1975-02-18 for composition for a hydrogel dilator article of manufacture and method for making same.
This patent grant is currently assigned to Polysciences, Inc.. Invention is credited to Murali Krishna Akkapeddi, Benjamin D. Halpern.
United States Patent |
3,867,329 |
Halpern , et al. |
February 18, 1975 |
Composition for a hydrogel dilator article of manufacture and
method for making same
Abstract
Composition, article of manufacture, and a method for forming a
hydrogel dilation device for use internal the human body. An
aqueous monomer solution, appropriate cross-linking agents, and
catalysts are inserted into a mold tube having a predetermined
internal contour shape. An inert gas is forced through the mixture
contained in the mold tube. The tube is sealed by inserting plugs
at opposing open tube ends. The mixture is then polymerized by
keeping the tube in a controlled temperature environment for a
predetermined length of time. A resulting moisture containing
hydrogen rod is extruded from the mold tube. Water soluble
impurities are removed from the hydrogel rod through dialysis in
distilled water. The hydrogel rod is then dried in a stream of air
until a predetermined percentage of the moisture is removed from
the hydrogel rod. The hydrogel rod is then placed in a vacuum
environment and heated for a predetermined length of time at a
particular temperature until substantially all of the moisture is
removed. An absorbant material may be inserted into the mold tube
before polymerization. The absorbant material extends external to
the hydrogel rod after formation and aids in transmitting body
fluids internal to the dilation rod.
Inventors: |
Halpern; Benjamin D.
(Jenkintown, PA), Akkapeddi; Murali Krishna (Feasterville,
PA) |
Assignee: |
Polysciences, Inc. (Warrington,
PA)
|
Family
ID: |
23087787 |
Appl.
No.: |
05/283,840 |
Filed: |
August 25, 1972 |
Current U.S.
Class: |
210/360.1;
502/402; 523/121; 524/787; 524/831; 525/61; 526/320; 523/105;
524/745; 524/833; 526/306; 606/192 |
Current CPC
Class: |
A61K
9/0034 (20130101); A61M 31/00 (20130101); A61M
29/00 (20130101) |
Current International
Class: |
A61K
9/00 (20060101); A61M 29/00 (20060101); A61M
31/00 (20060101); C08f 015/00 () |
Field of
Search: |
;260/8.3N,86.1E,86.1N,89.5A,89.5R,29.6H,17.4SG,73L,91.3VA
;128/341 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Goldstein; Melvin
Assistant Examiner: Woodberry; Edward
Attorney, Agent or Firm: Maleson; Paul Rosenberg; Morton
J.
Claims
1. A hydrogel composition comprising an intimate mixture on a
weight basis of: (A) about 5.0 to 30.0% of glyceryl
monomethacrylate in aqueous solution, said weight percentage of
said glyceryl monomethacrylate being taken with respect to said
aqueous solution; (B) about 0.2 to 4.5% of at least one diacrylate
cross-linker from the group consisting of diethylene glycol
diacrylate, tetraethylene glycol diacrylate and polyethylene glycol
diacrylate, said weight percentage of said diacrylate cross-linker
being taken with respect to said aqueous solution; (C) about 0.2%
of ammonium persulfate; and, (D) about 0.2% of sodium bisulfite,
said weight percentages of said ammonium persulfate and said sodium
bisulfite being taken with respect to said glyceryl
monomethacrylate in said aqueous
2. The hydrogel composition as recited in claim 1 wherein
composition (B)
3. The hydrogel composition as recited in claim 2 wherein
composition (A) includes an approximate glyceryl monomethacrylate
weight percentage
4. The hydrogel composition as recited in claim 2 wherein
composition (A) includes an approximate glyceryl monomethacrylate
weight percentage
5. The hydrogel composition as recited in claim 1 wherein
composition (B)
6. The hydrogel composition as recited in claim 5 wherein
composition (A) includes an approximate glyceryl monomethacrylate
weight percentage
7. The hydrogel composition as recited in claim 5 wherein
composition (A) includes an approximate glyceryl monomethacrylate
weight percentage
8. The hydrogel composition as recited in claim 1 wherein
composition (B)
9. The hydrogel composition as recited in claim 8 wherein
composition (A) includes an approximate glyceryl monomethacrylate
weight percentage
10. The hydrogel composition as recited in claim 8 wherein
composition (A) includes an approximate glyceryl monomethacrylate
weight percentage
11. A hydrogel composition comprising an intimate mixture on a
weight basis of: (A) about 5.0 to 30.0% of a monomer from the group
consisting of polyethylene glycol 4000 dimethacrylate and
polyethylene glycol 4000 diacrylate in aqueous solution, said
weight percentage of said polyethylene glycol 4000 diacrylate being
taken with respect to said aqueous solution; (B) about 0.2% of
ammonium persulfate; and (C) about 0.2% of sodium bisulfite, said
weight percentages of said ammonium persulfate and said sodium
bisulfite being with respect to said
12. The hydrogel composition as recited in claim 11 wherein
composition (A) includes an approximate polyethylene glycol 4000
diacrylate weight
13. The hydrogel composition as recited in claim 11 wherein
composition (A) includes an approximate polyethylene glycol 4000
diacrylate weight
14. A hydrogel composition comprising an intimate mixture on a
weight basis of: (A) about 1.5 to 10.0% of a monomer in aqueous
solution from the group consisting of polyethylene glycol 4000
diacrylate polyethylene glycol 4000 dimethacrylate, polyethylene
glycol 6000 diacrylate, and polyethylene glycol 6000 dimethacrylate
said weight percentage of said monomer being with respect to said
aqueous solution; (B) about 1.5 to 4.0% of a comonomer in aqueous
solution of acrylamide, said weight percentage of said comonomer
being with respect to said aqueous solution; (c) about 0.2% of
ammonium persulfate; and, (D) about 0.2% of sodium bisulfite, said
weight percentages of said ammonium persulfate and said sodium
bisulfite being taken with respect to said combined weight
percentage of said
15. The hydrogel composition as recited in claim 14 wherein
composition (A)
16. The hydrogel composition as recited in claim 15 wherein
composition (B)
17. The hydrogel composition as recited in claim 16 wherein said
weight of polyethylene glycol 4000 diacrylate approximates 4.0% by
weight of said
18. The hydrogel composition as recited in claim 17 wherein said
weight of
19. The hydrogel composition as recited in claim 16 wherein said
weight of polyethylene glycol 4000 diacrylate approximates 1.5% by
weight of said
20. The hydrogel composition as recited in claim 19 wherein said
weight of
21. The hydrogel composition as recited in claim 14 wherein
composition (A)
22. The hydrogel composition as recited in claim 21 wherein
composition (B)
23. The hydrogel composition as recited in claim 22 wherein said
weight of said polyethylene glycol 6000 diacrylate approximates
1.75% by weight of
24. The hydrogel composition as recited in claim 23 wherein said
weight of said acrylamide approximates 1.75% by weight of said
aqueous solution.
25. The hydrogel composition as recited in claim 22 wherein said
weight of said polyethylene glycol 6000 diacrylate approximates
1.5% by weight of
26. The hydrogel composition as recited in claim 25 wherein said
weight of said acrylamide approximates 1.5% by weight of said
acqueous solution.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention pertains to the field of dilators. In particular,
this invention relates to dilator mechanisms for insertion into the
body. More in particular, this invention pertains to cervical
dilators. Still further, this invention relates to hydrogel
composition dilators and methods of making same. This invention
pertains to a dilation mechanism which absorbs fluid and expands
continuously until a desired opening size has been attained.
2. Prior Art
Dilation devices and in particular cervical dilators are known in
the art. Some prior art includes chemical methods for dilation. One
type of chemical method is the use of slippery elm for cervical
dilation. This type of dilation is commonly referred to as a "folk
type" dilator and has been used for aborting processes. The use of
slippery elm apparently originated in Japan. The slippery elm
method employs the slippery elm tree bark which is inserted into
the cervix and absorbs moisture. The absorption of the moisture
causes swelling thereby distending the cervix. However, the use of
slippery elm has in a great many cases been found to cause
infection to the patient. Further, portions of the slippery elm has
been known to break and fall into the uterus. Other evidence has
been shown that the use of this method has led to a large number of
incomplete abortions.
Another chemical type dilator mechanism is laminaria tents made
from the root of a seaweed (laminaria digitata). The tent is dried
and made into a stick like contour. The stick is inserted into the
cervix and absorbs moisture from the patient. Absorption of the
moisture causes the laminaria tent to swell with a corresponding
distension of the cervix produced. However, the use of laminaria
tents has resulted in only a swelling ratio of approximately double
the initial insertion diameter after 2 to 3 hours within the
patient. This problem may have significant consequences in the fact
that the cervix may not be opened wide enough to allow for a
clinical abortion. Additionally, the time needed to achieve even a
swelling ratio of two times the initial insertion diameter may be
in excess of the time coincident with standard clinical
practices.
Mechanical dilators used for cervical dilation are known in the
art. In common usage, Hegar dilators comprising a set of increasing
diameter rod members are sequentially inserted into the cervix. Use
of such mechanisms may cause a traumitized condition in the patient
since this type of mechanical dilator causes a rapid and direct
cervical dilation. Use of such mechanisms may cause unacceptable
pain to the patient during the dilation process.
Other prior dilation mechanisms such as that disclosed in U.S. Pat.
No. 1,957,673 show insertion mechanisms having a cellulose core.
However, such is only used for absorption of fluid and does not
expand itself to cause the dilation process to proceed. Mechanical
devices having finger like extensions such as that described in the
Horton patent, U.S. Pat. No. 3,192,928 are known in the art.
However such devices may lead to a traumatized state in the patient
due to the rapid distension. Tampons having an additive of a
polyacrylamide copolymer are known such as that shown in the
Donohue patent, U.S. Pat. No. 3,628,534. However, such placement of
the tampon is in the vaginal canal and not in the cervix and is not
utilized for distension but merely for absorption of fluid. Other
dilation devices such as shown in the Shute patent, U.S. Pat. No.
3,626,949, the Eckard patent, U.S. Pat. No. 2,435,387 and the
Fogarty patent, U.S. Pat. No. 3,467,101 rely on inflatable
mechanisms to cause dilation. Such mechanisms may cause problems in
insertion ease as well as maintaining a controlled dilation of the
cervix.
SUMMARY OF THE INVENTION
An object of the subject invention is to provide a composition for,
as well as a method of making a chemically actuated dilation
device.
Another object of the instant invention is to provide a device
which will allow cervical dilation in a transient, controlled
manner.
A further object of the present invention is to provide a cervical
dilation device which is easy to use and simply insertable into the
patient.
A still further object of the subject invention is to provide a
dilation device which will absorb moisture and swell thereby
causing distension of the inserted body part.
Another object of the current invention is to provide a chemically
actuated dilation device that is easy to manufacture and includes
low manufacturing costs.
A method of forming a hydrogel rod for use as a dilator. The
initial step in the method is polymerizing an aqueous monomer
solution within a tube having a predetermined geometric contour to
form a moisture containing polymer hydrogel. The next step is
removing the moisture containing polymer hydrogel from the tube.
The polymer hydrogel substantially maintaining the geometric
contour of the tube to form a moisture containing hydrogel rod. The
hydrogel rod is then dried to form a substantially moisture free
dilation rod of predetermined dimensional contour.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the invention, there is hereinafter described a
composition for as well as a method of forming an article of
manufacture resulting in a hydrogel dilation device. The device is
formed in a rod like contour defining a cylinder or truncated cone
shape. The device may be inserted into the cervix or other body
opening which is to be dilated. Absorption of body fluid or other
fluid inserted into the dilation device causes it to expand. The
expanding hydrogel device forces the distension of a contiguous
body part.
A major use of the chemically actuated hydrogel dilation devices is
in the field of cervical dilation. Such uses include cervical
stenosis, endometrial biopsy, uterine currethe, drainage of uterine
cavity, placement and removal of intra uterine devices, radium
positioning, as an aid in inducing labor and clinical
abortions.
One composition prepared which provided a hydrogel with good
moisture absorbing volume increases and maintenance of satisfactory
structural characteristics resulted from the formation of
polyacrylamide gels. In the formation of this gel, the monomer used
was acrylamide, with the cross-linker being methylene
bis-acrylamide or hexamethylene diacrylamide and the catalytic
agents ammonium persulfate and .beta.-dimethyl aminopropionitrile.
The hydrogel compositions which were prepared included an intimate
mixture on a weight basis of about 1.0 to 10.1% of acrylamide in an
aqueous solution. The weight percentage of the acrylamide being
taken with respect to the aqueous solution. To this was added
between 0.01 to 0.2% of one of the cross-linkers from the group
consisting of methylene bis-acrylamide and hexamethylene
diacrylamide. The weight percentage of the cross-linkers used being
taken once again with respect to the aqueous solution. To these
components was added between 1.0 to 4.0% of ammonium persulfate and
1.0 to 4.0% of .beta.-dimethyl aminopropionitrile, to act as
catalytic agents.
The polyacrylamide gel thus prepared was formed by polymerization
of acrylamide in the presence of the above referenced cross-linkers
and catalytic agents. The aqueous acrylamide solution was inserted
or introduced into a series or plurality of molding tubes. The
composition of the mold tubes used was either polyethylene, teflon
or like material which would not react with the contained
components. Nitrogen gas was passed through the tubes for flushing
purposes. Concurrent with the nitrogen gas bring forced through the
tubes, methylene bis-acrylamide or hexamethylene diacrylamide were
introduced as the cross-linking agent. Additionally, a solution of
.beta.-dimethyl aminopropionitrile and ammonium persulfate were
added as catalytic agents. The tubes having an internal diameter
approximating 1.3 centimeters and a longitudinal dimension of about
12 centimeters were sealed or stoppered at the opposing open ends.
The contained mixture was then shaken in order to achieve a
substantially uniform mix. The components were polymerized when the
tubes were allowed to stand at room temperature for a predetermined
time within the approximate range of 30 minutes to 12 hours. In
some cases, the polymerization process took place at an elevated
temperature approximating 50.degree.C.
The resulting gels were moisture laden and removed from the tubes
by extrusion. Water soluble impurities were removed from the
resulting moisture containing gel rods or cylinders by dialysis in
distilled water. The gel rods were soaked or immersed in the
distilled water for several hours to ensure the dialyzing out of
low molecular weight compounds and residual redox catalyst
fragments.
The hydrogel rods were then dried initially in a stream of air
until approximately 10- 20% of moisture still remained in the rod.
The rods were then inserted into a vacuum chamber and dried at
approximately 50.degree.C. until substantially all of the moisture
had been removed from the composition.
In some cases agarose solution was added to the polymerization
mixture by weight percentage of the aqueous solution of between 0.2
to 1.0%, preferably about 0.5%. It was noted that the addition of
the agarose solution did increase the strength of the resulting
gels to some extent.
Another hydrogel composition formed resulted in polyglyceryl
monomethacrylate gels. These were prepared by redox initiated
polymerization of glyceryl monomethacrylate in water in the
presence of diacrylate cross-linker. The cross-linking agents
employed included diethylene glycol diacrylate (DEGDA),
tetraethylene glycol diacrylate (TEGDA) as well as polyethylene
glycol diacrylate (PEGDA). The catalytic agents used included
solutions of ammonium persulfate and sodium bisulfite.
The hydrogel compositions prepared included an intimate mixture on
a weight basis of about 10.0 to 20.0% of glyceryl monomethacrylate
in an aqueous solution. The weight percentage of the glyceryl
monomethacrylate being taken with respect to the aqueous solution.
To this was added between 0.2 to 4.5% of one of the diacrylate
cross-linkers diethylene glycol diacrylate, tetraethylene glycol
diacrylate or polyethylene glycol diacrylate. The weight percentage
of the particular diacrylate used being taken with respect to the
aqueous solution. To these components were added about 0.2% sodium
bisulfite and about 0.2% of ammonium persulfate acting as catalytic
agents. The weight percentages of the ammonium persulfate and
sodium bisulfite being taken with respect to the glyceryl
monomethacrylate in aqueous solution.
In preparation of the hydrogel dilation article of manufacture, the
aqueous solution of glyceryl monomethacrylate was inserted or
incorporated into the teflon or polyethylene tubes. Also introduced
was an appropriate diacrylate cross-linker followed by ammonium
sulfate. Purified nitrogen gas was passed through the tubes while
sodium bisulfite was introduced. The tubes were sealed with
sleeve-type rubber stoppers or some like device and heated for
several hours at a temperature approximating 50.degree.C. in order
for polymerization to take place.
The water containing hydrogel rods were removed from the mold tubes
by extrusion and soaked in distilled water between 8 and 12 hours.
The hydrogel rods were then dried by insertion into a room
temperature stream of air until 10.0 to 20.0% of moisture still
remains in the rod. The rods were then transferred to a vacuum
condition where they were then heated at approximately 50.degree.C.
until substantially all of the moisture was removed.
A hydrogel composition was prepared by polymerization of
polyethylene glycol 4,000 diacrylate in aqueous solution with
ammonium persulfate and sodium bisulfite as redox initiators or
catalytic agents. No cross-linker was used in this composition
since the monomer, namely polyethylene glycol 4,000 diacrylate is
bifunctional. The prepared hydrogel compositions in this set of
preparations included an intimate mixture on a weight basis of
about 6.0 to 15.0% of polyethylene glycol 4,000 diacrylate in
aqueous solution. The weight percentage of the catalytic, agents
ammonium persulfate and sodium bisulfite were taken with respect to
the polyethylene glycol 4,000 diacrylate in aqueous solution.
The preparation of the hydrogel dilation articles follow
essentially the same method as has been previously described. In
summary, the method included polymerizing the aqueous polyethylene
glycol 4,000 diacrylate solution with a tube having a predetermined
internal geometric contour. This resulted in the formation of a
moisture containing polymer hydrogel. The polymer hydrogel was
removed from the tube and dialyzed. Finally the hydrogel rod was
dried to a substantially moisture free form through combined air
stream impingement and vacuum condition heating.
A hydrogel composition defining a polyvinyl alcohol gel was
prepared by post-cross linking polyvinyl alcohol with different
amounts of glutaraldehyde under slightly acidic conditions. The
prepared hydrogel compositions in this experiment set included on
intimate mixture on a weight basis of about 2.0 to 4.0% of
polyvinyl alcohol in aqueous solution. As in all cases the weight
percentage of the polyvinyl alcohol was taken with respect to the
aqueous solution. To this was added about 0.04 to 0.16% by weight
of aqueous solution of glutaraldehyde acting as a cross-linking
agent. About 1.0% volume percentage of sulfuric acid taken with
respect to the aqueous solution was then added as a catalytic
agent.
Polyvinyl alcohol solution, dilute sulfuric acid, and
glutaraldehyde solution were incorporated into a series of teflon
or polyethylene tubes for molding purposes. As has been previously
described nitrogen gas was passed through the tubes. The tubes were
stoppered and placed in an oven for several hours. Oven temperature
was maintained at approximately 50.degree.C. The tubes were allowed
to cool and then immersed in water for dialysis for between 8 and
12 hours. The gels were dried or dehydrated by combined air stream
impingement and vacuum drying as has previously been discussed.
Another set of hydrogel dilation articles were prepared as
copolymer gels with either polyethylene glycol 4,000 diacrylate or
polyethylene glycol 6,000 diacrylate and comonomers of acrylamide
or methacrylyl galactose utilizing ammonium persulfate and sodium
bisulfite as catalytic agents. The hydrogel composition comprised
an intimate mixture on a weight basis of all components which
included about 1.5 to 4.0% of a monomer in aqueous solution taken
from the group consisting of polyethylene glycol 4,000 diacrylate
and polyethylene glycol 6,000 diacrylate. The weight percentage of
the monomer taken with respect to the aqueous solution. To this was
added 1.5 to 4.0% by weight of aqueous solution of a comonomer in
aqueous solution from the group consisting of acrylamide and
methacrylyl galactose. To this was added the catalytic agents of
about 0.2% ammonium persulfate and about 0.2% of sodium bisulfite
taken with respect to the weight of the monomer and comonomer.
In typical preparation experiment, solutions of the comonomers were
mixed in a mold tube. Solutions of ammonium persulfate followed by
sodium bisulfite were added while concurrently nitrogen gas was
passed through the tube. The tube was stoppered and maintained at a
temperature approximating 50.degree.C. for 3 to 12 hours. The gels
were removed and immersed in distilled water for several hours. The
gels were then air dried initially and finally under vacuum
conditions at a temperature approximating 40.degree.C.
A further hydrogel composition was prepared which included on a
weight percentage basis of aqueous solution about 4.0 to 10.0% of
2-acrylimido 2-deoxyglucose in aqueous solution. To this was added
about 0.12 to 0.09% of methylene bis-acrylamide acting as the
cross-linking agent. The method of preparation in this set was
similar to that previously discussed for the above
compositions.
In the manner discussed, there was formed a series of hydrogel rod
articles of manufacture suitable for use as a dilation device. The
rods have a predetermined contour similar to the internal shape of
the mold tubes used which were cylindrical in nature or in a
truncated cone shape to possibly aid in insertion into the body.
The final hydrogel rod produced which were found to be suitable for
use as a cervical dilator had longitudinal extensions between 4 to
8 centimeters and diameters between 3 to 5 centimeters although
such is not critical to the inventive concept. Additionally, it was
found convenient in an embodiment of the invention to include a
moisture absorbing material passing internal to the hydrogel rod
and partially exposed. Cotton thread or some like material was used
in actual practice. In this embodiment of the invention, the
preparation of the rods are the same as in that previously
described with the exception that the absorbing material is
inserted into the tube before the addition of monomers,
crosslinking agents, and catalysts.
The general formula for polyethylene glycol diacrylate and
polyethylene glycol dimethacrylate may be written: ##SPC1##
where:
R=h for polyethylene glycol diacrylate
R=--ch.sub.3 for polyethylene glycol dimethyacrylate
where:
N=approximately 90 for polyethylene glycol 4000 diacrylate and
dimethacrylate.
N=approximately 150 for polyethylene glycol 6000 diacrylate for
dimethacrylate.
The transestirification reaction for making polyethylene glycol
6000 diacrylate may be written:
HO[CH.sub.2 --CH.sub.2 --O--.sub.N H +2CH.sub.2 =CHCO.sub.2 C.sub.2
H.sub.5.sup.TPT CH.sub.2 =CHCOO[CH.sub.2 --CH.sub.2 --O--.sub.N
COCH=CH.sub.2 +2C.sub.2 H.sub.5 OH
A mixture of polyethylene glycol 6000 (Carbowax 6000, 400 g.),
ethyl acrylate (2 liters), phenothiazine (0.5 g.), and nitrobenzene
(0.13 ml.) were heated at 100.degree.C with a reflux ratio
controller while stirring under a slow stream of dry nitrogen. The
first 40 ml. of the liquid was distilled off in order to remove the
moisture from the system. Then the contents were allowed to reflux
and 5 ml. of tetraisopropyltitanate (duPont, Tyzor `TPT`) catalyst
was added. The reaction mixture was then allowed to heat at 50%
reflux ratio for 3 hours and then under a slow, complete
distillation for 5 hours. The temperature of the bath was
maintained below 100.degree.C to prevent thermal polymerization of
the reaction mixture. After about 1,400 ml. of distillate was
collected, the reaction mixture was cooled to room temperature and
then poured into about 4 liters of 1:1 mixture of diethyl ether and
petroleum ether. The solid which precipitated out was filtered
under suction. The crude solid was extracted with hot water
(80.degree.-90.degree.C) and filtered. The clear aqueous filtrate
was concentrated under reduced pressure at 40.degree. to
50.degree.C in a rotary evaporator. The clear syrupy liquid was
treated with 400 ml. benzene and distilled to remove the last
traces of water as an azeotrope. The residue thus obtained formed a
waxy solid under cooling. The solid was dissolved in minimum amount
of hot benzene (60.degree.C) and precipitated in an excess of
diethyl ether. The granular white solid is polyethylene glycol 6000
diacrylate.
The solid was further purified by treatment with active carbon. An
aqueous solution of the compound was stirred with a small quantity
of the active carbon for 3 hours and filtered. The clear aqueous
solution was concentrated at reduced pressure at
40.degree.-50.degree.C and last traces of water was removed by
azeotropic distillation with benzene. The residue was dissolved in
minimum quantity of benzene and precipitated in an excess of
diethyl ether. The pure, granular white solid was filtered and
dried in vacuo (mp 56.degree.-60.degree.C, 70% yield).
The above procedure was also used for the preparation of
polyethylene glycol 4000 diacrylate wherein polyethylene glycol
4000 (Carbowax 4000) was the starting material. Similarly
polyethylene glycol 6000 dimethyacrylate was prepared from
polyethylene glycol 6000 and methyl methacrylate and polyethylene
glycol 4000 dimethacrylate was prepared from polyethylene glycol
4000 and methyl methacrylate.
The following example sets illustrate the hydrogel compositions and
methods of preparation as has been herein described.
EXAMPLE SET 1
__________________________________________________________________________
% CROSS % CROSS % SWELLING SWELLING EXP MONOMER LINKER LINKER AGA
ROSE RATIO TIME
__________________________________________________________________________
1 10.0% MBA 0.02% -- 11.7 24 hrs. 2 10.0% MBA 0.01% -- 13.2 24 hrs.
3 5.0% MBA 0.5% -- 15.7 5 days 4 5.0% MBA 0.05% -- 21.6 5 days 5
5.0 MBA 0.01% -- 39.6 5 days 6 5.0% MBA 0.2% 0.5% 10.1 24 hrs. 7
5.0% MBA 0.1% 0.5% 18.4 5 days 8 5.0% MBA 0.01% 0.5% 19.3 5 days 9
2.0% MBA 0.05% 0.5% 17.7 5 days 10 2.0% MBA 0.002% 0.5% 18.8 24
hrs. 11 1.0% MBA 0.02% 0.5% 19.5 24 hrs. 12 10.0% HMDA 0.05% --
9.46 24 hrs. 13 10.0% HMDA 0.01% -- 17.6 24 hrs. 14 5.0% HMDA 0.05%
-- 25.1 5 days 15 5.0% HMDA 0.02% 0.5% 12.6 24 hrs. 16 5.0% HMDA
0.002% 0.5% 10.0 24 hrs. 17 2.0% HMDA 0.02% 0.5% 16.4 24 hrs. 18
2.0% MHDA 0.004% 0.5% 20.7 24 hrs. 19 2.0% HMDA 0.001% 0.5% 19.5 24
hrs.
__________________________________________________________________________
A series of experiments were completed with the object of producing
hydrogel compositions which are useful as dilator instruments. As
shown in example set No. 1 polyacrylamide gels using methylene
bis-acrylamide (MBA) and hexamethylene diacrylamide (HMDA) as
cross-linking agents were produced. The monomer used is acrylamide
in aqueous solution whose weight percentage is that of the aqueous
solution. The cross-linking agent weight percentage (of MBA or
HMDA) is also of the aqueous solution weight, as in the agarose
weight percentage (when agarose was used in the making of the
hydrogel composition). The polyacrylamide gels of experiment set
No. 1 were prepared through polymerization of acrylamide in the
presence of .alpha., w-diacrylamide as cross-linker using a redox
initiator ammonium persulfate/.beta.-dimethylamino propionitrile
about 1.0 to 4.0% by weight of the acrylamide was used for both the
ammonium persulfate and .beta.-dimethylamino propionitrile. For
each experiment a mold tube was used approximating a length of 12
cm. and an internal diameter of 1.3 cm. Composition of the mold
tubes was polyethylene. The mold tubes were flushed with an inert
gas (nitrogen being used in the example set No. 1). Concurrent with
the passage of nitrogen through each tube particular weight
percentages of aqueous acrylamide solution (monomer) were
incorporated in a particular mold tube. Additionally, measured
quantities of cross-linker solution (MBA or HMDA), agarose solution
(where used in the experiment set), and the catalyst solution of
.beta.-dimethyl aminopropronitrile/ammonium persulfate (about 2.0%
each by weight of the monomer) were added to the tube mixture. The
tubes were closed and shaken to attain a substantially uniform
mixture. The enclosed compositions were allowed to stand for
varying lengths of time at room temperature, however, it was noted
that gels formed in most cases within 30 minutes.
The gels were dehydrated by controlled vacuum drying at room
temperatures. Prior to the drying process it was found useful to
soak the gels in distilled water for several hours in order to
dialyze out any low molecular weight compounds and residual redox
catalyst fragments.
The swelling ratios were defined and measured by immersing a known
weight of dehydrated polymer sample in distilled water at room
temperature for a specified amount of time. The swollen polymer gel
is then withdrawn, the surfaces dried and weighed. The ratio
between the weight of swollen polymer and the dry weight of the
polymer is defined as the swelling ratio.
EXAMPLE SET 2
__________________________________________________________________________
% CROSS % CROSS % SWELLING SWELLING EXP MONOMER LINKER LINKER RATIO
TIME
__________________________________________________________________________
1 18.0 DEGDA 4.5 -- -- 2 19.0 DEGDA 0.95 -- -- 3 19.0 DEGDA 0.47 --
-- 4 18.0 TEGDA 4.5 -- -- 5 19.0 TEGDA 1.9 -- -- 6 19.0 TEGDA 0.95
-- -- 7 19.0 TEDGA 0.47 -- -- 8 10.0 DEGDA 1.0 16.8 7 days 9 10.0
DEGDA 0.5 13.6 7 days 10 10.0 TEGDA 1.0 13.3 7 days 11 10.0 TEGDA
1.0 13.3 7 days 12 10.0 TEGDA 0.8 13.9 7 days 13 10.0 PEGDA 0.2
15.4 2 days
__________________________________________________________________________
Example set No. 2 experiments were prepared by redox initiated
polymerization of glycerol monomethacrylate in water solution (% of
monomer refers to weight percentage of the aqueous solution), and
in the presence of a diacrylate used as a cross-linker. The
specific cross-linking agents used included diethylene glycol
diacrylate (DEGDA), tetraethylene glycol diacrylate (TEGDA) and
polyethylene glycol diacrylate (PEGDA). Ammonium persulfate and
sodium bisulfite were used as a catalyst and each had an
approximate weight percentage of 0.2% by weight of the monomer.
Monomer solution, cross-linker and ammonium persulfate were
introduced into a series of polyethylene mold tubes. Concurrent
with the passage of nitrogen through the mold tubes, sodium
bisulfite solution was introduced. The tubes were sealed with
sleeve-type rubber stoppers and heated at approximately
50.degree.C. for several hours. The resulting gels were soaked in
distilled water for a period of 8-12 hours. The gels were then
dehydrated under vacuum. Swelling ratios and swelling times were
measured as has been previously described.
EXAMPLE SET 3 ______________________________________ EXP % MONOMER
SWELLING RATIO SWELLING TIME ______________________________________
1 15.0 -- -- 2 12.0 10.7 5 days 3 10.0 12.8 5 days 4 10.0 16.2 5
days 5 9.0 8.3 2 days 6 8.0 13.3 2 days 7 7.0 15.5 2 days 8 6.0
20.4 2 days ______________________________________
Experiment set 3 was initiated to prepare a hydrogel composition by
polymerization of polyethylene glycol 4000 diacrylate (monomer) in
aqueous solution with ammonium persulfate and sodium bisulfate as a
redox initiator. No cross-linking agent was used as the monomer is
found to be difunctional. The method of preparation of the gels
used in this experiment set, as well as their dehydration is
similar in nature to the processes as hereinbefore described in
experiment sets 1 and 2.
EXAMPLE SET 4 ______________________________________ % % SWELLING
SWELLING EXP MONOMER LINKER RATIO TIME
______________________________________ 1 4.0 0.12 7.3 2 days 2 4.0
0.08 6.7 2 days 3 4.0 0.04 5.0 2 days 4 4.0 0.06 4.15 2 days 5 4.0
0.02 5.1 2 days 6 4.0 0.032 3.8 2 days 7 3.0 0.096 7.05 2 days 8
3.0 0.08 5.8 2 days 9 3.0 0.06 11.6 2 days 10 3.0 0.16 7.6 2 days
11 2.0 0.08 -- -- 12 2.0 0.064 -- -- 13 2.0 0.040 -- --
______________________________________
Polyvinyl alcohol (monomer) was post-cross linked in aqueous
solution with varying amounts of glutaraldehyde under slightly
acidic conditions as shown in Example set 4. The per cent of
monomer is the weight percentage of the polyvinyl alcohol with
respect to the aqueous solution. The per cent of cross-linker
glutaraldehyde is the weight percentage of the glutaraldehyde with
respect to the aqueous solution. A catalytic agent of sulfuric acid
was used where 0.1 ml. of sulfuric acid was incorporated into 10.0
ml. of the reaction mixture. Additionally, experiments were run
using high molecular weight polyethylene oxide compositions such as
Polyox commercially available from Union Carbide Corp. In such
cases radiation was used for cross-linking.
A solution of polyvinyl alcohol was made by initially swelling the
polymer in distilled water through heating. The resulting mixture
was homogenized in a blender and reheated to a homogeneous solution
that was transparent. The polyvinyl alcohol solution, dilute
sulfuric acid and varying amounts of glutaraldehyde solution were
put into a plurality of appropriately sized mold tubes. The tubes
were sealed and placed into an oven maintained at 50.degree.C. for
several hours. The resulting gels were immersed in water for
between 8-12 hours. As previously described the gels were
dehydrated.
Where a 2.0% polyvinyl alcohol solution was used, it was found that
the resulting gels were very soft and were difficult to dry into a
rod shape. The 3.0 and 4.0% polyvinyl solutions showed good rod
structure after the drying process.
EXAMPLE SET 5
__________________________________________________________________________
MONOMER % MONOMER MONOMER % SWELLING EXP I I II MONOMER RATIO II (3
hours)
__________________________________________________________________________
1 PEGDA4000 4.0 acrylamide 4.0 300 2 PEGDA4000 1.5 acrylamide 1.5
540 3 PEGDA6000 1.75 acrylamide 1.75 457 4 PEGDA6000 1.5 acrylamide
1.5 510 5 PEGDA4000 4.0 MAG 4.0 426 6 PEGDA4000 2.5 MAG 2.5 454
__________________________________________________________________________
In each experiment a particular weight percentage of either
polyethylene glycol 4000 diacrylate (PEGDA 4000) or polyethylene
glycol 6000 diacrylate (PEGDA 6000) was mixed with either
acrylamide or methacrylyl galactose (MAG). The weight percentages
of the monomers being taken with respect to an aqueous solution of
the monomers. Solutions of the comonomers were mixed in a mold
tube. Nitrogen was bubbled through the tube and about 0.2% of
ammonium persulfate as well as 0.2% of sodium bisulfite was added.
The weight percentages of the ammonium persulfate and sodium
bisulfite being taken with respect to the combined weight
percentages of the two monomers being mixed. The tubes were sealed
and heated at 50.degree.C. for 3 to 12 hours. The resulting gels
were removed and immersed in distilled water for several hours. The
gels were air dried initially at room temperature and then under
vacuum at approximately 40.degree.C.
EXPERIMENT SET 6 ______________________________________ EXP %
MONOMOMER % CROSS LINKER % SWELLING (3 hours)
______________________________________ 1 10.0 0.09 701 2 6.0 0.012
980 3 4.0 0.035 1190 ______________________________________
The monomer used in this experiment set was 2-acrylamide
2-deoxyglucose in aqueous solution. The percentage of monomer and
cross-linker refers to the percentage by weight of the aqueous
solution. The cross-linker used was methylene bis-acrylamide. The
monomer and cross-linker were mixed together in the particular
percentages shown. The mixture was added to mold tubes and the same
procedure outlined in the preceding example sets were followed to
produce the hydrogel composition.
* * * * *