US3867329A

US3867329A - Composition for a hydrogel dilator article of manufacture and method for making same

Info

Publication number: US3867329A
Application number: US283840A
Authority: US
Inventors: Benjamin D Halpern; Murali Krishna Akkapeddi
Original assignee: Polysciences Inc
Current assignee: Polysciences Inc
Priority date: 1972-08-25
Filing date: 1972-08-25
Publication date: 1975-02-18
Anticipated expiration: 1992-02-18

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.

Description

United States Patent [191 Halpern et al.

[4 1 Feb. 18, 1975 1 COMPOSITION FOR A HYDROGEL DILATOR ARTICLE OF MANUFACTURE AND METHOD FOR MAKING SAME [75] Inventors: Benjamin D. Halpern, .lenkintown;

Murali Krishna Akkapeddi, Feasterville, both of Pa.

[73] Assignee: Polysciences, Inc., Warrington, Pa. [22] Filed: Aug. 25, 1972 [21] Appl. No.: 283,840

[52] US. Cl 260/29.6 I-I, 128/341, 260/17.4 SG, 260/73 L, 260/803 N, 260/861 E, 260/861 N,

. 2 018224180189;Mammy x [51] Int. Cl. C08f 15/00 [58] Field of Search..... 260/803 N, 86.1 E, 86.1 N, 260/895 A, 89.5 R, 29.6 H, 17.4 SG, 73 L,

[56] References Cited UNITED STATES PATENTS 2,976,576 3/1961 Wichtele 260/861 3,061,595 10/1962 Dorion et al 260/803 3,080,207 3/1963 Tanabe et al. 260/73 L 3,101,991 8/1963 Fukushima et al 260/73 L 3,252,904 5/1966 Carpenter 260/803 3,281,400 10/1966 Kunze 260/803 3,467,614 9/1969 Dinges et al. 260/803 3,580,879 5/1971 Higashimura 260/803 3,681,269 8/1972 Heitz et a1. 260/895 A 3,699,089 10/1972 Wichterle 260/861 R27,40l 6/1972 Wichterle 260/861 FOREIGN PATENTS OR APPLICATIONS 1,186,479 4/1970 Great Britain 260/861 E Primary ExaminerMelvin Goldstein Assistant Examiner-Edward Woodberry Attorney, Agent, or Firm-Paul Maleson; Morton J. Rosenberg [57] 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.

26 Claims, No Drawings COMPOSITION FOR A HYDROGEL DILATOR ARTICLE OF MANUFACTURE AND METHOD FOR MAKING SAME 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 digimra). 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 correspon ding 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, US 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, US. 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, US. Pat. No. 3,626,949, the Eckard patent, US. Pat. No. 2,435,387 and the Fogarty patent, US. Pat. No. 3,467,10l 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 acomposition 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 bisacrylamide or hexamethylene diacrylamide and the catalytic agents ammonium persulfate and B-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 B-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 ,B-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 50C.

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 -20% of moisture still remained in the rod. The rods were then inserted into a vacuum chamber and dried at approximately 50C. 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 50C. 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 ap proximately 50C. until substantially all ofthe 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 crosslinker 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 aleohol 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 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 50C. 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 galaetose 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 ofa 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 50C. 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 40C.

A further hydrogel composition was prepared which included on a weight percentage basis of aqueous solution about 4.0 to 10.0% of Z-acrylimido 2- dcoxyglucose 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.

1n 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:

where:

R=H for polyethylene glycol diacrylate R=-CH for polyethylene glycol dimethyacrylate where:

N=approximately 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:

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 C with a reflux ratio controller while stirring under a slow stream of dry nitrogen. The first 40 ml. ofthe 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 100C to prevent thermal polymerization of the reaction mixture. After about 1,400 m1. 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 (8090C) and filtered. The clear aqueous filtrate was concen trated under reduced pressure at 40 to 50C 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 dis solved in minimum amount of hot benzene (60C) 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 ofthe 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 40-50C and last traces of water was removed by azeotropic distillation with benzeneThe 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 5660C, 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 15 EXAMPLE SET 1 for both the ammonium persulfate and B-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. l). 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 solutin (where used in the experiment set), and the catalyst solution of fi-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 CROSS CROSS SWELL- SWELL- lNG ING EXP MONO- LlNKER LINKER AGA ROSE RATIO TIME MER 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 percent g e is t hatof theaqueous solution. The crosslinking 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. l were prepared through polymerization of acrylamide in the presence of a, wdiacrylamide as cross-linker using a redox initiator ammonium persulfate/B-dimethylamino propionitrile about 1.0 to 4.0% by weight of the acrylamide was used 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 specifled 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 9 EXAMPLE SET 2-Cominued CROSS CROSS SWELL SWELLlNG lNG EXP MONO- LlNKER LlNKER RATIO TIME MER 10 10.0 TBS A 1.0 13.3 7 7 days 11 10.0 TEGDA 1.0 13.3 7 days 12 10.0 TEGDA 0.8 13.9 7 days 10.0 PEGDA 0.2 15.4

2 days Example set No. 2 experiments were prepared by redox initiated polymerization of glycerol monometh- EXAMPLE SET 4 acrylate in water solution of monomer refers to SWELL SWELUNG weight percentage of the aqueous solution), and in the XP lNG presence of a diacrylate used as a cross-1inker. The spe- E MONOMER UNKER RATIO TIME cific cross-linking agents used included diethylene gly- 1 (H2 2 days col diacrylate (DEGDA), tetraethylene glycol diacryg g8 382 g g 3 0 late (TEGDA) and polyethylene glycol diacrylate 4 i g; (PEGDA). Ammonium persulfate and SOdlUITl bisulfite 5 2 y were used as a catalyst and each had an approximate g 2:8 883% 3:3 weight percentage of 0.2% by weight of the monomer. 8 3.0 0.08 5.8 days Monomer solution, cross-linker and ammonium per- 9 2 days 10 3.0 0.16 7.6 2 days sulfate were introduced into a series of polyethylene 11 2.0 0.08 mold tubes. Concurrent with the passage of nitrogen g-g 88% through the mold tubes, sodium bisulflte solution was V introduced. The tubes were sealed with sleeve-type P l l l h l I k d rubber stoppers and heated at approximately 50C. for o yvmy o m was i several hours. The resulting gels were soaked in dis- L g g Y fi$ g tilled water for a period of 8-12 hours. The gels were y e um er S lg y con Ions as 7 own ample set 4. The per cent of monomer is the weight then dehydrated under vacuum. Swelling ratios and ercent ofthe 1 Vin la] ho] with res act to the swelling times were measured as has been previously p age p0 y y co p described aqueous solutlon. 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 EXAMPLE SET 3 was incorporated into 10.0 ml. of the reaction mixture.

Additionally, experiments were run using high molecu- EXP MONOMER SWELLING SWELLING TIME lar weight polyethylene oxide compositions such as Po- RATIO lyox commerclally available from Union Carbide Corp. 1 15.0 In such cases radiation was used for cross-linking. 2 110 107 5 days 40 A solution of polyvinyl alcohol was made by initially 3 10.0 12.8 5 days h l d. d h h h 4 100 162 sdays swe mgt epo ymer 1n 1st1 e watert roug eating. 5 9.0 8.3 2 days The resulting mixture was homogenized in a blender g 38 332;: and reheated to a homogeneous solution that was trans- 3 :0 20:4 2 days parent. The polyvinyl alcohol solution, dilute sulfuric acid and varying amounts of glutaraldehyde solution h were put into a plurality of appropriately sized mold tubes. The tubes were sealed and placed into an oven maintained at C. for several hours. The resulting Experiment set 3 was initiated to prepare a hydrogel gels were immersed in water for between 8-12 hours. composition by polymerization of polyethylene glycol 50 As previously described the gels were dehydrated. 4000 diacrylate (monomer) in aqueous solution with Where a 2.0% polyvinyl alcohol solution was used, it ammonium persulfate and sodium bisulfate as a redox was found that the resulting gels were very soft and initiator. No cross-linking agent was used as the monowere difficult to dry into a rod shape. The 3.0 and 4.0% mer is found to be difunctional. The method of prepapolyvinyl solutions showed good rod structure after the i?" f h $9 25?? lilii fi sti zs a drying Process EXAMPLE SET 5 MONOMER MONO- SWELL- MONQMER MER ING EXP I II MONO- RATIO MER ll (3 hours) 1 PEGDA4000 40 acrylamide 4.0 300 2 PEGDA4000 15 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 their dehydration is similar in nature to the processes as hereinbefore described in experiment sets 1 and 2.

In each experiment a particular weight percentage of either lys hy ses slysq 5. 999 .diasr ts (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 50C. 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 40C.

EXPERIMENT SET 6 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.

What is claimed is:

l. 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 bisulfiteQsaid weight percentages of said ammonium persulfate and said sodium bisulfite being taken with respect to said glyceryl monomethacrylate in said aqueous solution.

2. The hydrogel composition as recited in claim 1 wherein composition (B) is diethylene glycol diacrylate.

3. The hydrogel composition as recited in claim 2 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating 10.0% of said aqueous solution.

4. The hydrogel composition as recited in claim 2 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating 20.0% of said aqueous solution.

5. The hydrogel composition as recited in claim 1 wherein composition (B) is tetraethylene glycol diacry late.

6. The hydrogel composition as recited in claim 5 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating l0.0% of said aqueous solution.

7. The hydrogel composition as recited in claim 5 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating 20.0% of said aqueous solution.

8. The hydrogel composition as recited in claim 1 wherein composition (B) is polyethylene glycol diacrylate.

9. The hydrogel composition as recited in claim 8 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating l0.0% of said aqueous solution.

10. The hydrogel composition as recited in claim 8 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating 20.0% of said aqueous solution.

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 polyethylene glycol 4000 diacrylate in said aqueous solution.

12. The hydrogel composition as recited in claim 11 wherein composition (A) includes an approximate polyethylene glycol 4000 diacrylate weight percentage approximating 5.0% of said aqueous solution.

13. The hydrogel composition as recited in claim 11 wherein composition (A) includes an approximate polyethylene glycol 4000 diacrylate weight percentage approximating 30.0% of said aqueous solution.

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 monomer and said comonomer.

15. The hydrogel composition as recited in claim 14 wherein composition (A) is polyethylene glycol 4000 diacrylate. I

16. The hydrogel composition as recited in claim 15 wherein composition (B) is acrylamide in said aqueous solution.

17. The hydrogel composition as recited in claim 16 wherein said weight of polyethylene glycol 4000 diacrylate approximates 4.0% by weight of said aqueous solution.

18. The hydrogel composition as recited in claim 17 wherein said weight of acrylamide approximates 4.0% by weight of said aqueous solution.

wherein said weight of said polyethylene glycol 6000 diacrylate approximates 1.75% by weight of said aqueous solution.

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 said aqueous solution.

26. The hydrogel composition as recited in claim 25 wherein said weight of said acrylamide approximates 1.5% by weight of said acqueous solution.

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 SOLUTION.

5. The hydrogel composition as recited in claim 1 wherein composition (B) is tetraethylene glycol diacrylate.

6. The hydrogel composition as recited in claim 5 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating 10.0% of said aqueous solution.

9. The hydrogel composition as recited in claim 8 wherein composition (A) includes an approximate glyceryl monomethacrylate weight percentage approximating 10.0% of said aqueous solution.

15. The hydrogel composition as recited in claim 14 wherein composition (A) is polyethylene glycol 4000 diacrylate.

19. The hydrogel composition as recited in claim 16 wherein said weight of polyethylene glycol 4000 diacrylate approximates 1.5% by weight of said aqueous solution.

20. The hydrogel composition as recited in claim 19 wherein said weight of acrylamide approximates 1.5% by weight of said aqueous solution.

21. The hydrogel composition as recited in claim 14 wherein composition (A) is polyethylene glycol 6000 diacrylate in said aqueous solution.

22. The hydrogel composition as recited in claim 21 wherein composition (B) is acrylamide in said aqueous solution.

23. The hydrogel composition as recited in claim 22 wherein said weight of said polyethylene glycol 6000 diacrylate approximates 1.75% by weight of said aqueous solution.