Patent Application
20190153150
This invention relates to hydrogels, and more particularly to improved elastic epoxy hydrogel polymers and their use.
Hydrogels are a class of polymer chain products that are water-insoluble. Hydrogels are highly absorbent polymer materials and are used in various applications, including biomedical applications.
The present invention provides improvements in hydrogel polymers by providing unique super elastic epoxy hydrogel polymers formed by reacting a polyetheramine with a polyglycidyl ether. The resulting polymer is a super elastic hydrogel having various applications.
Further features and advantages of the present invention will be seen from the following detailed description, taken in conjunction with the accompanying drawings, wherein like numerals depict like parts, and wherein
The epoxy hydrogel of the present invention can be produced by mixing ratios of ether reactants such as polyethylene glycol diglycidyl ether and polyoxyalkyleneamines and H2O resulting in an aqueous polymerization of the materials. Particularly preferred are polyoxyalkyleneamines such as commercially available from Huntsman Corporation under the brand name JEFFAMINE® and other polyether amines as an epoxy component that is reacted with various ethers to form epoxy hydrogels. The polyoxyalkyleneamines contain primary amino groups attached to the terminus of a polyether backbone. They are thus “polyether amines.” The polyether backbone is based either on propylene oxide (PO), ethylene oxide (EO), mixed propylene oxide/ethylene oxide or may contain other backbone segments and varied reactivity provided by hindering the primary amine or through secondary amine functionality. The material can be cured using heat to speed up the reaction or cured at room temperature over, e.g. 24 hrs. This produces a very wide material handling time window for manufacturing purposes and in the liquid state can be easily poured into molds of various shapes. When the polymer has cured it is extremely flexible, elastic and has expansion ratios of over 1,000% of its dry state volume. Aqueous solutions or solvents may be used for polymerization, and the solvent may be selected from the group consisting of a monomer, polyether amine, a glycidyl ether, and a combination thereof.
The polyether amine may be selected from the group consisting of polyoxyalkyleneamine, and a (poly)alkylene glycol having amino or alkylamino termini selected from the group consisting of polyethylene glycol amine, di-(3-aminopropyl) diethylene glycol, polyetherdiamine, polyoxypropylenediamine, polyoxyethylenediamine, and triethyleneglycol diamine. Furthermore, the polyether amine may have a molecular weight ranging from 1 to 5,000 and may be selected from the group consisting of a monoamine, a diamine, a triamine, a quaternary amine and a mixture thereof.
The polyglycidyl ether may be selected from the group consisting of diethylene glycol diglycidyl ether; ethylene glycol diglycidyl ether; 1,3-butanediol diglycidyl ether; poly(propylene glycol) diglycidyl ether; poly(dimethylsiloxane), diglycidyl ether terminated; neopentyl glycol diglycidyl ether; neopentyl glycol diglycidyl ether, brominated; cyclohexanedimethanol diglycidyl ether, mixture of cis and trans, glycerol diglycidyl ether; diglycerol polyglycidyl ether; glycerol polyglycidyl ether; bisphenol A diglycidyl ether, bisphenol A diglycidyl ether, brominated; bisphenol S diglycidyl ether; bisphenol F diglycidyl ether; bis[4-(glycidyloxy)phenyl]methane; 1,4-butanediyl diglycidyl ether; 4-butanediol diglycidyl ether; bisphenol A propoxylate diglycidyl ether; 1,3-bis(2,3-epoxypropoxy)benzene; 1,3-diglycidyloxybenzene; resorcinol diglycidyl ether; diglycidylresorcinol; diglycidyl resorcinol ether; resorcinol diglycidyl ether; hydroquinone diglycidyl ether; 2,2′-[1,3phenylenebis(oxymethylene)]bisoxirane; m-bis(2,3-epoxypropoxy)benzene; meta-bis(glycidyloxy)benzene; resorcinol bis(2,3-epoxypropyl)ether; trimethylolpropane triglycidyl ether; sorbitol polyglycidyl ether; polyglycerol polyglycidyl ether; pentaerythritol polyglycidyl ether; trimethylolpropane polyglycidyl ether; polyethylene glycol diglycidyl ether; glycidyl ester ether of p-hydroxy benzoic acid; 1,6-hexanediol diglycidyl ether; terephthalic acid diglycidyl ester, and a mixture thereof prior to curing, both the polyether amine and the polyglycidyl ether may be hydrophilic; or alternatively, one of the polyether amine and polyglycidyl ether may be hydrophilic and the other may be hydrophobic.
Other materials may be added during the liquid polymerization to produce unique epoxy polymers with added functionality or to change the physical properties of the cured epoxy hydrogel. For example, by adding an oxide, such as titanium oxide to the liquid epoxy mixture the porosity and texture volume of the polymer will change into a white sponge like material that still performs like a hydrogel. These properties can be further amplified by irradiation of the materials by wavelengths in both the visible spectrum and non visible spectrums of light. The TiO loaded epoxy hydrogel when hydrated will oxidize water or other fluids when it is exposed to UV. This same polymer also works as a glucose detection material when hydrated with blood or interstitial fluid and irradiated. The high surface area within the porous TiO loaded hydrogel structure makes a very efficient hydrogen production media that is extremely low cost and easily manufactured. The added oxide may also be selected from the group consisting of a metal oxide, a mineral oxide, a chemical oxide, and a combination thereof. Also, the oxide may be used as a chemical catalyst, photo catalyst, or electrical catalyst.
An electrically conductive material may also be added. The electrically conductive material may be selected from the group consisting of a conductive polymer, a metal, a carbon, a mineral, an oxide, an acid, a salt, and a combination thereof. The electrically conductive material may also be a nanopowder. Finally, the electrically conductive material may be a liquid solution or suspended in a liquid solution.
A photo-responsive or a photo-sensitive material may also be added. The photo-responsive or photo-sensitive material may be selected from the group consisting of a laser dye, a photo oxidizer, a photo acid generator, a photo initiator, a photosensitizing electron transport material, a hole transport material, a polyaniline, a liquid crystalline material, a photo-luminescent material, a photo-luminescent polymer, a fluorescent polyamides, a fluorescent monomer, a light emitting conjugated polymer, a poly(fluorenylene ethynylene) (PFE), a polyfluorene (PFO), a polyacetylene, a polypyridine, a polythiophene, a poly(phenylene ethynylene) (PPE), a polyphenylene vinylene (PPV), a light emitting dopant functionalized polymer, a light emitting organometallic complex, a triplet emitter, a phthalocynine dye, a porphyrin dye, a chromatography dye, and a combination thereof.
The elastic epoxy hydrogel of the present invention also works very well as an ionic actuator material and exhibits superior pressure generation from the swelling kinetics of the amines over other hydrogel or polymer gel actuators. By increasing the density or the number of the amine groups such as secondary and primary amines an increase in swelling pressure is attained in the hydrogel. This also has an effect on the swelling and deswelling times. One way of achieving this is by incorporating Polyamidoamine (PAMAM) polyether dendrimers, poly(propylene imine PPI-dendrimers, amino functionalized dendrimers, or combinations thereof, as part of the polymer structure. Dendrimers are highly branched and offer superior numbers of polymer linkage points. They also are commercially available with primary amino surface groups and core amino groups. This makes engineering of the hygrogel possible so that specific performance parameters such as the pressure the gel can produce is determined by formula ratios of materials or by controlling the organization, size and number of branches in polymer structure itself. Hydrogel density and porosity is controlled by amount of amine functionality and molecular weight of the polyether amines.
Hydrogel density and porosity is also controlled by amount of polyethylene glycol diglycidyl ether and/or by the ratio of H2O or solvent used to polymerize the materials. A preferred ether for this gel is polyethyleneglycol-dodecylether (polyEGDE), but other ethers also can be used such as cyclohexanedimethanol diglycidyl ether. These ethers produce a very clear and strong hydrogel that reacts hydrophobicly to high pH aqueous solutions and swells when exposed to low pH or acidic solutions. Hydrogel density and porosity can also be controlled by adding amount of oxidizer to the polymer during polymerization. Whether in solution or dry these oxidizers can be further activated chemically electrically or by photons during polymerization to achieve desired properties.
Ionic hydrogel swelling kinetics are achieved by the difference in pH, ions, cations or protons between the solution outside of the hydrogel and the solution inside of the hydrogel or the polymer composition of the hydrogel. These performance characteristics can be controlled several ways. For example, adding acid to the polymer during polymerization creates a hydrogel that has a higher pH swelling property. Hydrogel swelling kinetics also can be controlled by adding salts or alkali solutions to the polymer during polymerization. This is accomplished by chemical, electrical, electrochemical, photo or photochemical excitation of the epoxy polymer or solution that it is hydrated with.
It is possible to create an electro activated polymer (EAP) by hydrating the epoxy hydrogel in an electrolyte, inserting an electrode into the gel, and spacing a second electrode a short distance from the hydrogel and running low amounts of current through the electrodes. For example, epoxy hydrogel swelling may be increased in the region of a platinum electrode using saline as an electrolyte fluid. When the polarity is reversed, the hydrogel will deswell or contract. Control of hydrophobic and hydrophilic properties also can be achieved by these methods. This same material in a different configuration can also by used as an artificial muscle material or even used to construct an artificial organ.
One drawback of EAP materials for industrial actuation purposes is that the power needed to scale up the technology is prohibitive both in the sheer magnitude and cost. The development of a reversible ionic photo activated polymer (IPAP) actuator material is a way to circumvent the prohibitive power needs and gain industrial acceptance of polymer actuator materials. By doping electro active or ionic polymers with photo reversible ionic sources it is possible to create similar response characteristics to that of ionic EAP actuators. The power needed to drive a single light source would inherently be much less that needed to drive individual EAP actuators as size of application increased, this reduction in power would also be multiplied by the number of actuators in a given system. It is also theorized that the speed of actuation cycles would be increased by diffuse irradiation throughout the material. Even more attractive is the possibility of the material being activated from natural daylight irradiation and the need for electrical power eliminated.
The invention will be further described with reference to the following examples.
EAP actuator hydrogels were prepared by reacting the cross linking agent, JEFFAMINE® T-403 available from Huntsman Corporation, with a diepoxide such as an ethylene glycol diglycidyl ether alphatic difunctional epoxy monomer such as EGDGE available from Dedrich Chemical Company, or GE-PEG500-GE available from General Electric Company. The first generation of actuators consisted of cross linking EGDGE and JEFFAMINE® T-403.
This formulation took into account the 50% purity of the EGDGE. It was determined by 1H and 13C NMR spectroscopy that the impurities in the EGDGE sample from Aldrich contained no additional epoxide residues. The overall process is as follows: a test tube was charged with EGDGE (174 mg, 1.0 mmol, 348 mg of 50% EGDGE), JEFFAMINE® T-403 (391 mg, 0.89 mmol), and water (739 mg). The resulting polymer precursor was mixed thoroughly and allowed to age at room temperature for 0 or 45 minutes (see Table 1). The reaction mixture was then poured into the mold and allowed to cure at 70° C. for 1 hour. The mold, with cured material, was removed from the heat and allowed to cool to room temperature. After cooling, the molded material was hydrated to a state of equilibrium in an electrolyte and are ready to be used as an actuator, or the hydrated material can encapsulated by a flexible material to eliminate and drying out of the hydrogel actuator.
The gelation degree and degree of swelling were based on Lendlein and co-workers. The experiment was conducted as follows: the mass of the actuator (mi) was taken after it had been cured and air-dried for 24 hours. The actuators were then placed in water and allowed to soak for more than 24 hours. The mass of the hydrated actuator (mh) was then taken. These swollen actuators were then removed from the water and allowed to air-dry for 24 hours. This new dried mass (m) was then measured. The table shows the gelation degree and degree of swelling for all the actuators studied.
The formula for the gelation degree (G) is as follows:
The swelling degree (Q) of the actuators extracted in water is calculated as follows:
where ρgel is the density of the gel after extraction. The density of the gel was taken after extraction in its dry state. The actuators were almost perfect cylinders and the dimensions were used to calculate the volume, and along with the mass (m), the density (ρgel) could be determined.
aRatio of amine hydrogens to epoxide residues.
b50% (Tech.).
cGE-PEG500-GE.
dStirred during aging time.
Ionic photo activated polymers (IPAP) were prepared by the addition of the following materials to the polyether amine and polyglycidyl ether compositions due to their well known photo induced pH swings, excitation spectrum, and relative non hazardous properties, Methylene Blue 0.05% solution (Aldrich) λmax 664 nm, 7 diethylamino-4-methyl coumarin (Aldrich Chemical Company) λmax 390 and a photo acid generator (PAG) diphenyliodonium perfluoro-1-butanesulfonate (Aldrich) λmax 203 nm.
Each of the dry materials were added in varying amounts to the gel formulation typically in increments of 10 mg up 40 mg. Methylene Blue solution was also added incrementally by substituting increasing portions of the H2O with Methylene Blue solution at 50%, 100% substitution rates.
Coumarin IPAP hydrogels were formulated by adding the 7 diethylamino-4-methyl coumarin to the PolyEDGE (Aldrich Chemical Company) first then adding JEFFAMINE® T 403 (Huntsman Chemicals) and H2O, the 7 diethylamino-4-methyl coumarin dissolved well at 10 mg and 20 mg, but reside increasingly remained at the 30 mg and 40 mg formulations with large clumps forming at the bottom of the mold at 40 mg. The liquid was poured into Teflon® molds and cured for 2 hours at 70° C. The gels were then allowed to air dry for 24-48 hours. Following the cure process the gels were hydrated with distilled H2O and allowed to soak over 24 hours. The 10-20 mg gels appeared clear yellow, the 30 mg gels appeared hazy yellow and the 40 mg gels appeared hazy and speckled and fell apart at the bottom portion of the mold.
Photo acid generator IPAP hydrogels were formulated by adding 10 mg of the diphenyliodonium perfluoro-1-butanesulfonate was added to the PolyEDGE and dissolved well, JEFFAMINE® T403 was then added followed by H2O to complete the polymerization. The material was then poured into molds and cured for 2 hours at 70° C. Gels were then allowed to air dry for 24-48 hours and then hydrated with H2O for 24 hours, 2 samples were set aside and soaked in a solution of sodium perchlorate 0.1N.
Methylene Blue IPAP hydrogels were formulated using a Methylene Blue 0.05% solution following the above protocol. The Methylene Blue was added with the H2O step in the aqueous polymerization 50% substitution and then 100% substitution. The material was then poured into molds and cured for 2 hours at 70° C. Gels were then allowed to air dry for 24-48 hours, the samples were then hydrated with H2O for 24 hours, 2 samples were set aside and soaked in a solution of sodium perchlorate 0.1N.
The Methylene Blue gel and the PAG gel hydrated with the sodium solution experienced much faster contraction speed upon irradiation then the same gels in H2O. These gels experienced full contraction in less than 15 minutes and had some fracturing due to this rapid deswelling of the gel. This rapid deswelling ion flow indicates it should be possible to make a dry composite actuator using an ion exchange membrane and clear exterior polymer layer of a hydrophobic photo sensitized polymer.
Hydro gel structures of the present invention that can be engineered to have various or varying porosity for various uses such as actuators, drug delivery, drug therapy, wound healing, absorbent, filter material, filtration system, porous tissue scaffolding, porous blood vessel and capillary scaffolding, porous encasement or surface for bio implantable devices and sensors, porous encasement or surface for bio implantable prosthesis and parts, porous encasement or surface for implantable cell cultures, porous encasement or surface for cell cultures, porous encasement or surface for chemical and biological cultures, porous substrate or coating for bio and chemical sensors. A particularly advantageous application is in pulse activated pump systems as described in PCT application Nos. PCT/US04/05922 and PCT/US05/45210, the contents of which are incorporated herein in their entirety, by reference. Other uses are where a porous and flexible hydrogel substrate or coating would improve the properties or performance or features of an existing product.
The hydrogels of the present invention can be used in situ by injecting mixed epoxy components into desired area within the body, such as to replace or repair a disc between vertebrae in the spinal area. The epoxy will cure in situ and expand to the desired volume by absorbing interstitial fluid or by injecting a fluid into the epoxy once it has cured. The injected fluid can be something as simple as saline buffered to match the hydrogel pH responsive swelling. As a drug or other delivery device the epoxy can be loaded with a desired material in wet or dry form and then implanted and allowed to hydrate naturally from body fluids or have the hydration fluids injected. Once the implanted epoxy hydrogel is hydrated the drug can leach out or the epoxy hydrogel material can be stimulated via the bodies natural ph response, using electric current, photon irradiation or combination of these to contract and deliver the desired material or drug at a desired rate. The implanted material can also be refilled via injection if needed.
Epoxy and other hydrogels can be used as buoyancy devices and buoyancy control for micro and small unmanned underwater vehicles (UUV), large UUV, submarines and other submersibles, personnel floatation devices, sensor platforms, buoys, chemical or biological material release mechanisms for aqua farming etc.
By controlling flow of fluids in and out of the gel, positive, negative and neutral buoyancy can be achieved from a polymer gel. Hydrophobic control via chemical, electrical or photo activation can control the timing and amount of materials or chemicals to be released in an aqueous environment. Hydrogels swollen with water can go to great depth due to the polymer structure being surrounded by the environment it is in, and the fact that it does not contain any compressible or expandable gasses. Activation of the gel can produce ion flow out of the gel forcing the gel to swell. Activation of hydrogels with reactive dopants such as TiO also can produce gasses in or around the gel enabling the gel to rise or increase its buoyancy. The same effect can be accomplished by controlling the hydrophobic or hydrophilic properties of the gel.
Hydrogels of the present invention also can also be used as a bacteria, microbe or other biological material growing media where in the microbe produces an end product, chemical or reaction that is desired, for example, as a hydrated hydrogel containing a marine microbe that produces a chemical when exposed to light. A photo sensitive hydrogel would start to expel fluid that it is hydrated while the microbe is producing the desired chemical. This becomes an efficient pump or delivery system that needs very little to sustain it, yet can operate on a continuous cycle or in reaction to a change in its surrounding environment. In this way it becomes a living chemical, environmental or biological sensor that can produce a signal or even a counter reaction, in and around it as the surrounding changes occur. This is efficient for the hydro farming of fish and other food sources that need to be in an aqueous environment or aqueous solutions provided to them.
The pH gradient within the polymer structure is changed from its surrounding environment when exposed to irradiation in the same light spectrum the doped polymer is designed to react to, creating an ionic flow either into or out of the polymer structure that is photo activated. By sandwiching the non-transparent membrane or ionic polymer between the photo-activated layers, motion is achieved by the contraction or expansion of the opposing sides with the outer layer that is sealing the entire structure.
A similar effect can be achieved by doping the hydrating solution or electrolyte of the hydrogel with photo oxidizers, photo acid generators, photo initiators or laser dyes such as but not limited to these materials that the gel is hydrated with, creating a photolyte or photolytic solution. The solution will reversibly change its pH when irradiated with energy in an on and off manner causing the polymer to swell or deswell according to the resulting change in the pH in and around the polymer structure. The described devices and applications of the invention are not intended to limit the scope of the invention, these are only a few of the many applications possible.
The IPAP material also can be used as a new photo responsive composite and act similar to a plant, by bending towards or tracking the sunlight during a daylight cycle. A simple practical application is a pole for solar panels. The pole would bend towards the sun, being the shrinking or contracting side of the composite, and it would be exposed to direct sunlight and tip or angle the attached solar panel towards the sun. This could be done using no electricity at all and therefore increasing the efficiency of solar panels. Another possibility of commercial use is water pumps that do not need electricity and can pump in response to daylight cycles or with a simple mechanical shutter that would open and close according to the size of the actuator.
Referring now to the drawings, there is illustrated an exemplary use of a photo activated polymer gel in accordance with the present invention in a sealed structure or actuator with an external semi rigid or flexible outer layer (3) that allows a desired amount of light through to the next layer of the photo activated polymer (1) then by using a membrane (4) or another gel (2) that does not allow light through but does allow ions to pass or flow through to the photo activated polymer layers on each side of it or surrounding it. In this configuration it is possible to build an actuator or device such as a stand for a solar cell that will bend in the direction of the sun. This provides a non-electrical method of tracking the sun for the most efficient exposure angle of the photovoltaic to the sun's rays but does not use any electricity making a more energy efficient system.
There are many other products that this could be used in such as pump mechanisms that work without electricity. All that would be needed are light and dark cycles, such as day and night, to provide the movement needed to pump or composite structures that unfold when exposed to light or other radiation. This is possible by the same ion flow that is driven by electricity in the electro active polymers but by using photo oxidizers, photo acid generators, photo initiators or laser dyes but not limiting the invention to these materials, the pH gradient within the polymer structure is changed from its surrounding environment when exposed to irradiation in the light spectrum the doped polymer is designed to react to, creating an ionic flow either into or out of the polymer structure that is photo activated. By sandwiching the non-transparent membranes (4) or ionic polymer (2) between the photo activated layers (1), motion is achieved by the contraction or expansion of the opposing sides with the outer layer (3) sealing the entire structure.
Still other changes are possible without departing from the spirit and scope of the invention.
This application is a continuation patent application of U.S. patent application Ser. No. 12/373,245, filed Jan. 9, 2009, which claims benefit of PCT International Patent Application Serial No. PCT/US07/73188, filed Jul. 10, 2007, which in turns claims benefit of U.S. Provisional Application Ser. No. 60/806,918, filed Jul. 10, 2006, the entire disclosure of which is incorporated herein by reference.
This invention was made in part with Government support under contract number W81XWH-06-C-0057 awarded by the U.S. Army Medical Research Command. The Government may have certain rights in the invention.
| Number | Date | Country | |
|---|---|---|---|
| 60806918 | Jul 2006 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12373245 | Jan 2009 | US |
| Child | 16252250 | US |
