Intraluminal Devices and Polymers

Abstract

Various embodiments relate to compositions for use in intraluminal devices and methods of using the compositions in intraluminal devices. The compositions include two parts: a first part including a first solution and a second part including a second solution, wherein the first solution includes one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders and additives, and the second solution includes a polymerization initiator or co-initiator, a non-aqueous solvent, and optionally one or more chain extenders and additives.

Description

[Technical Field]

[0001] Cross-reference to related patent applications This application claims priority to U.S. Provisional Patent Application No. 62 / 575,827, filed October 23, 2017, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION The embodiments disclosed herein generally relate to compositions for use in intraluminal devices and methods of using the compositions in intraluminal devices. Various embodiments relate to biostable organogels and methods of treating aneurysms. [Background technology]

[0002] An aneurysm is a swelling or bulge in a blood vessel that is often prone to rupture and therefore poses a significant risk to the patient. Aneurysms can occur in any blood vessel, but are of particular concern when they occur in the cerebral vasculature or a patient's aorta. Abdominal aortic aneurysms (AAAs) are classified based on their location within the aorta and their shape and complexity. Aneurysms found below the renal arteries are called infrarenal abdominal aortic aneurysms. Suprarenal abdominal aortic aneurysms occur above the renal arteries. Thoracic aortic aneurysms (TAA) occur in the ascending, arch, or descending portions of the upper aorta. Infrarenal aneurysms are the most common, representing approximately 70% of all aortic aneurysms. Suprarenal aneurysms are less common, representing approximately 20% of aortic aneurysms. Thoracic aortic aneurysms are the least common and are often the most difficult to treat. The most common form of aneurysm is the "fusiform" form, in which the swelling extends around the entire circumference of the aorta. Less commonly, aneurysms may be characterized by a bulge attached to a constriction on one side of the vessel. Thoracic aortic aneurysms are often dissecting aneurysms resulting from hemorrhagic separation of the aortic wall, usually the medial layer. The common treatment for each of these types and forms of aneurysm is open surgical repair. Open surgical repair has been completely successful in patients who are otherwise reasonably healthy and have no significant comorbidities. However, such open surgical procedures are problematic because access to the abdominal and thoracic aorta is difficult to achieve and the aorta must be clamped, placing significant strain on the patient's heart. Recently, endoluminal grafts have become widely used to treat aortic aneurysms in patients. Generally, in endoluminal repair, the aneurysm is accessed "intraluminally" through one or both of the common iliac arteries. A graft is then implanted. A successful endoluminal approach has a much shorter recovery period than an open surgical approach.

[0003] A typical endograft procedure utilizes the placement of a stent-graft to treat aneurysms. It would be desirable to provide improved compositions, methods, systems, and graft prostheses that result in minimal or no leakage, resist migration, are relatively easy to deploy, and are capable of treating most or all aneurysm morphologies. It would further be desirable to provide endoluminal graft filling structures and compositions that have biocompatibility, biodegradability, viscosity, stability, and a balanced set of mechanical properties of flexibility and strength suitable for withstanding the in vivo environment. At least some of these objectives will be achieved by the techniques described below. Summary of the Invention

[0004] Various embodiments relate to a composition comprising two parts, a first part comprising a first solution and a second part comprising a second solution, wherein the first solution comprises one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders and additives, and the second solution comprises a polymerization initiator or co-initiator, a non-aqueous solvent, and optionally one or more chain extenders and additives. Various embodiments relate to an organogel comprising the composition. In various embodiments, the prepolymer comprises a compound having at least two functional groups selected from acrylate, methacrylate, or vinyl functional groups. In various embodiments, the prepolymer is selected from the group consisting of ethoxylated (3) bisphenol A diacrylate, ethoxylated (30) bisphenol A diacrylate (EBPADA), ethoxylated (9) trimethylolpropane triacrylate, ethoxylated (15) trimethylolpropane triacrylate, ethoxylated (20) trimethylolpropane triacrylate (PEG-T), propoxylated (3) trimethylolpropane triacrylate (PTMPTA), pentaerythriol triacrylate, ethoxylated (4) pentaerythritol tetraacrylate, pentaerythritol tetraacrylate, and methacrylic variants thereof, divinyl adipate, 1,4-dibutanediol divinyl ether, di- and triethylene glycol divinyl ether, allyl ether, diallyl maleate, trimethylpropane diallyl ether, and combinations thereof.

[0005] In various embodiments, the non-aqueous solvent comprises an aliphatic and aromatic solvent selected from the group consisting of alcohols, aldehydes, amides, carbonates, ethers, esters, glycols, glycol ethers, glycol esters, hydrocarbons, ketones, sulfoxides, and vegetable oils. In various embodiments, the non-aqueous solvent is selected from the group consisting of methanol, glycerin, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, tripropylene glycol, polyethylene glycol, ethyl ether, tripropylene glycol methyl ether, di(propylene glycol) butyl ether, propylene carbonate, butylene carbonate, benzene, toluene, xylene, methyl ethyl ketone, castor oil, linseed oil, sesame oil, soybean oil, olive oil, and combinations thereof.

[0006] In various embodiments, the chain extender comprises a mono- or di-functional compound having acrylate, methacrylate, or vinyl functionality. In various embodiments, the chain extender is selected from the group consisting of polyethylene glycol monoacrylate (PEGMA), polypropylene glycol monoacrylate (PPGMA), polyethylene glycol diacrylate (PEGDA), polypropylene glycol diacrylate (PPGDA), dipropylene glycol diacrylate (DPGDA), tetraethylene glycol diacrylate (TEGDA), tripropylene glycol diacrylate (TPGDA), polyethylene glycol monomethacrylate (PEGMMA), polypropylene glycol monomethacrylate (PPGMMA), polyethylene glycol methyl ether methacrylate (PEGMEMA), polyethylene glycol dimethacrylate (PEGDMA), polypropylene glycol dimethacrylate (PPGDMA), and combinations thereof.

[0007] In various embodiments, polymerization initiators include peroxides and hydroperoxides. In various embodiments, the polymerization initiator is selected from the group consisting of benzoyl peroxide (BPO), cumene hydroperoxide (CHP), dicumyl peroxide (CPO), lauryl peroxide, tert-amyl hydroperoxide (t-AHP), tert-butyl hydroperoxide (t-BHP), di-tert-butyl peroxide (DTBP), tributyl hydroperoxide (TBPH), tetra-methylbutyl hydroperoxide (MBHP), and combinations thereof. In various embodiments, the polymerization co-initiator is selected from the group consisting of triethanolamine (TEA), 1-(2-pyridyl)-2-thiourea (PTU), 1-acetyl-2-thiourea (ATU), N,N-dihydroxyethyl-p-toluidine (DHEPT), 4-(di-methylamino)phenethyl alcohol (DMAPE), 4-(dimethylamino)ethyl benzoate (EDMAB), 2-[4-(dimethylamino)phenyl]ethanol, N,N-dimethyl-p-toluidine (DMPT), bis(hydroxyethyl)-p-toluidine, and combinations thereof. In various embodiments, either or both of the first and second solutions further comprise a co-solvent. In various embodiments, the co-solvent is selected from the group consisting of nonanol, dimethyl sulfoxide, butylene carbonate, diethylene glycol ethyl ether, dipropylene glycol methyl ether, dipropylene glycol butyl ether, tripropylene glycol methyl ether and tripropylene glycol butyl ether, and combinations thereof.

[0008] In various embodiments, the composition further comprises one or more additives. In various embodiments, the one or more additives are selected from the group consisting of fillers, contrast agents, processing aids, plasticizers, and viscosity reducers. Various embodiments relate to a method of forming an organogel, comprising: delivering a composition comprising a first solution and a second portion comprising a second solution to a site where the organogel is intended to form; contacting the first solution with the second solution; and initiating polymerization of prepolymers to form the organogel, wherein the first solution comprises one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders and additives, and the second solution comprises a polymerization initiator or co-initiator, a non-aqueous solvent, and optionally one or more chain extenders and additives. In various embodiments, the one or more additives are selected from the group consisting of fillers, contrast agents, processing aids, plasticizers, and viscosity reducers.

[0009] In various embodiments, the composition exhibits a compressive modulus of from about 1 MPa to about 18 MPa. In various embodiments, the composition exhibits a gel time of from about 1 minute to about 20 minutes. Various embodiments relate to a system for treating aneurysms comprising a filling structure filled with a composition comprising two parts, a first part comprising a first solution and a second part comprising a second solution, wherein the first solution comprises one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders and additives, and the second solution comprises a polymerization initiator or co-initiator, a non-aqueous solvent, and optionally one or more chain extenders and additives. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 illustrates a prosthetic system mounted on a delivery catheter and including a filling structure that can be filled with the composition of the present technology. [Figure 2] FIG. 2 illustrates the use of the prosthetic system of the embodiment of FIG. 1 to treat an infrarenal abdominal aortic aneurysm. [Figure 3]3 illustrates a system including a pair of prostheses for delivery to an infrarenal abdominal aortic aneurysm, where each prosthesis is mounted on a delivery catheter and includes a filling structure that can be filled with a composition of the present technology. [Figure 4] FIG. 4 illustrates the use of an embodiment of the prosthetic system of FIG. 1 to treat an infrarenal abdominal aortic aneurysm. [Figure 5] Figures 5A, 5B, 5C, and 5D illustrate prepolymers with various functional groups in accordance with embodiments of the present technology. Figure 5E provides a legend for the shapes in Figures 5A, 5B, 5C, and 5D. [Figure 6] FIG. 6 illustrates the formation of an organogel composition according to an embodiment of the present technology. DETAILED DESCRIPTION OF THE INVENTION

[0011] Various embodiments are described below. It should be noted that these specific embodiments are not intended to be exhaustive or limiting of the broader aspects described herein. An aspect described in connection with a particular embodiment is not necessarily limited to that embodiment and may be practiced in any other embodiment.

[0012] As used herein, "about" is understood by those of ordinary skill in the art and will vary to some extent depending on the context in which it is used. If there are uses of the term that would not be clear to persons of ordinary skill in the art given the context in which it is used, "about" will mean up to plus or minus 10% of the particular term. The use of the terms "a," "an," "the," and similar referents in the context of describing elements (particularly in the context of the claims below) should be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated herein as if it were individually recited herein. All methods described herein may be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to facilitate understanding of the embodiments and does not impose limitations on the scope of the claims, unless otherwise stated. No language in the specification should be construed as indicating any non-claimed element as essential. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0013] Ratios, concentrations, amounts, and other numerical data may be presented in range format herein. It should be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values ​​stated as the limits of the range, but also all individual numerical values ​​or subranges subsumed within the range, as if each numerical value and subrange were expressly stated. For example, 5 to 40 mole % should be interpreted not only to include the express limit of 5 to 40 mole %, but also to include subranges such as 10 mole % to 30 mole %, 7 mole % to 25 mole %, etc., and individual amounts within the stated range, including fractions such as 15.5 mole %, 29.1 mole %, and 12.9 mole %.

[0014] As used herein, the term "organogel" refers to a type of gel consisting of a liquid organic phase within a three-dimensional crosslinked network. As used herein, the term "initiator" refers to an element that initiates the gelation process of a hardenable composition. In some cases, the term "initiator" as used herein refers to one part of an initiator system. For example, a two-part initiator system can be used, where one part is included in the hardenable composition and the other part is provided separately. This other part, provided separately, is referred to as a "co-initiator" in the present invention. As used herein, "substantially water-free" means that the water content of the composition is less than about 1% of the total weight of the composition. "Substantially non-aqueous" or "having a low water content" means that the amount of water in the composition, if any, is small, less than about 1.0%, preferably less than about 0.5%, more preferably less than about 0.2%. For example, the compositions described herein may be substantially water-free, or substantially non-aqueous, or have a low water content. Water is not an intended component of the composition, but may be present in small amounts as an impurity. However, typically, the compositions described herein do not contain water.

[0015] Methods for using endobags or fillable structures to treat AAA generally involve generating a material in situ by increasing the volume of the expandable member of a medical device. The expandable member is typically filled with a filler material, such as polyethylene glycol (PEG) or another polymer, that can polymerize in situ in the presence of water to form a hydrogel. The hydrogel material conforms to the aneurysm being treated and also serves to secure the medical device in place. The material is generated by polymerization of a polymer precursor (prepolymer) mixed with a crosslinker and one or more free-radical initiators and / or co-initiators. Polymerization can be performed, for example, inside an endograft, including a single- or double-walled bag such as an endobag. It has now been discovered that organogel materials with excellent stability and desirable mechanical properties can be produced and used as a filler material for the expandable member of a medical device.

[0016] In various embodiments, the present technology provides biocompatible organogels for therapeutic applications, such as the treatment of abdominal and thoracic aortic aneurysms. The organogels are formed from a hardenable composition, which includes one or more gellable prepolymers that can harden or denature in situ at the intended application site in response to an initiator system, and are configured to undergo a change in its physical state to retain a desired shape and position. The hardenable composition formed from the prepolymers, and optionally other components, can be delivered to the intended application site. The properties of the hardenable composition, such as viscosity, vary depending on the intended end use of the composition. The composition is delivered to the intended site by an appropriate delivery device, such as a catheter or syringe. Before, during, or after delivery, the composition is exposed to an initiator system and undergoes one or more of hardening, crosslinking, and gelation to provide an organogels-containing device.

[0017] In one embodiment, a composition is provided that includes two parts, at least one of which includes a prepolymer in a non-aqueous solvent that forms an organogel when the two parts are mixed together. The composition includes a prepolymer that can rapidly crosslink to form an organogel after delivery to the intended site. The composition includes one or more non-aqueous solvents, a polymerization aid, such as a redox component, and may further include additives and active agents. The composition is suitable for forming an organogel in situ at the intended application site. Typically, all components that contribute to the formation of the organogel are soluble in the non-aqueous solvent.

[0018] In various embodiments, a composition is provided that includes two parts: a first part containing a first solution and a second part containing a second solution. In various embodiments, the composition includes two parts: a first part containing a first solution and a second part containing a second solution, where the first solution includes one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders and additives, and the second solution includes a polymerization initiator or co-initiator, a non-aqueous solvent, and optionally one or more chain extenders and additives. Although various embodiments are generally described with respect to two solutions, the present technology may also include a composition that includes a first part containing a solution and a second part containing a solid (e.g., a powder), or both parts may contain solids rather than solutions of the respective components.

[0019] The prepolymer may include a multifunctional crosslinkable prepolymer. The multifunctional prepolymer may include similar or different functional groups. In various embodiments, the prepolymer includes a compound including at least one functional group selected from acrylate, methacrylate, vinyl, or allyl functional groups. In various embodiments, a compound including at least one functional group may react with another compound containing a functional group selected from acrylate, methacrylate, vinyl, or allyl functional groups to form a covalent bond. In various embodiments, the prepolymer includes a compound including at least two functional groups selected from acrylate, methacrylate, vinyl, or allyl functional groups. In at least one embodiment, suitable prepolymers include, but are not limited to, acrylate, methacrylate, vinyl, and allyl compounds based on polyethylene glycol. Some examples of such compounds include PEG acrylates and methacrylates selected from ethoxylated (3) bisphenol A diacrylate, ethoxylated (30) bisphenol A diacrylate (EBPADA), ethoxylated (9) trimethylolpropane triacrylate, ethoxylated (15) trimethylolpropane triacrylate, ethoxylated (20) trimethylolpropane triacrylate (PEG-T), propoxylated (3) trimethylolpropane triacrylate (PTMPTA), pentaerythritol triacrylate, pentaerythritol tetraacrylate, ethoxylated (4) pentaerythritol tetraacrylate, and methacrylic variants thereof, as well as vinyl and allyl compounds selected from divinyl adipate, 1,4-dibutanediol divinyl ether, di- and triethylene glycol divinyl ether, allyl ether, diallyl maleate, trimethylpropane diallyl ether, and the like, and mixtures thereof. In an illustrative embodiment, the prepolymer comprises ethoxylated (20) trimethylolpropane triacrylate. In at least one embodiment, the prepolymer has an average molecular weight ranging from 100 to 8000. Exemplary prepolymers with various functional groups are illustrated in Figures 5A, 5B, 5C, and 5D.Figure 5E shows a legend for the shapes in Figures 5A, 5B, 5C, and 5D. Although the exemplary dimer, trimer, and tetramer compositions depicted in some of the figures have identical functional groups, the functional groups on the dimers, trimers, and tetramers could all be the same type or any combination of the various functional groups disclosed herein.

[0020] The prepolymer can be added in an amount suitable to obtain an organogel with the desired properties. The prepolymer can be present in an amount of about 1% to about 80% by weight of the total weight of the composition, including about 5% to about 75%, about 10% to about 70%, about 15% to about 65%, about 20% to about 60%, about 25% to about 55%, about 30% to about 50%, or about 35% to about 45% by weight of the total weight of the composition, including any two of these values, or a range less than any one of these values. In an illustrative embodiment, the prepolymer is present in an amount of about 10% to about 40% by weight of the total weight of the composition.

[0021] The first solution and optionally the second solution may or may not contain a non-aqueous solvent. The non-aqueous solvent may be one that dissolves the prepolymer and other components while being inert to all reactants. Suitable non-aqueous solvents include, but are not limited to, aliphatic and aromatic solvents, such as, but not limited to, alcohols, aldehydes, amides, carbonates, ethers, esters, glycols, glycol ethers, glycol esters, hydrocarbons, ketones, and sulfoxides, vegetable oils and fats, and the like, and combinations thereof, as well as other non-aqueous solvents known to those skilled in the art. Illustrative solvents include, but are not limited to, methanol, glycerin, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, tripropylene glycol, polyethylene glycol, ethyl ether, tripropylene glycol methyl ether, di(propylene glycol) butyl ether, propylene carbonate, butylene carbonate, benzene, toluene, xylene, methyl ethyl ketone, dimethyl sulfoxide, castor oil, linseed oil, sesame oil, soybean oil, olive oil, and the like, as well as mixtures thereof.

[0022] The non-aqueous solvent may be present in the composition in an amount of about 1% to about 90% by weight, which may include about 5% to about 80%, about 10% to about 70%, about 15% to about 65%, about 20% to about 60%, about 25% to about 55%, about 30% to about 50%, or about 35% to about 45% by weight of the non-aqueous solvent based on the total weight of the composition. In various embodiments, the first and second solutions can comprise about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90% by weight of non-aqueous solvent, inclusive of any two of these values, or in a range less than any one of these values. In illustrative embodiments, the first solution comprises about 20% to about 80% by weight of one or more non-aqueous solvents. In illustrative embodiments, the second solution comprises about 20% to about 80% by weight of one or more non-aqueous solvents. In illustrative embodiments, the non-aqueous solvent is present in an amount of about 10% to about 40% by weight of the total weight of the composition.

[0023] In addition to the prepolymer and solvent, the composition may optionally contain one or more chain extenders. The properties of the organogel can be modified by the appropriate selection of the chain extender. For example, a chain extender can be used to penetrate the tightly crosslinked network of the organogel and increase its toughness. Suitable chain extenders are soluble in non-aqueous solvents and can co-polymerize with the prepolymer or form a separate network within the organogel structure. Chain extenders can include difunctional and / or monofunctional extending monomers. In various embodiments, suitable chain extenders include any mono- or difunctional acrylate, methacrylate, vinyl, or allyl compound. Examples of such suitable chain extenders include, but are not limited to, polyethylene glycol monoacrylate (PEGMA), polypropylene glycol monoacrylate (PPGMA), polyethylene glycol diacrylate (PEGDA), polypropylene glycol diacrylate (PPGDA), dipropylene glycol diacrylate (DPGDA), tetraethylene glycol diacrylate (TEGDA), tripropylene glycol diacrylate (TPGDA), polyethylene glycol monomethacrylate (PEGMMA), polypropylene glycol monomethacrylate (PPGMMA), polyethylene glycol methyl ether methacrylate (PEGMEMA), polyethylene glycol dimethacrylate (PEGDMA), polypropylene glycol dimethacrylate (PPGDMA), and the like, and mixtures thereof.

[0024] The chain extender may suitably have a number average molecular weight (Mn) in the range of about 200 to about 25,000 daltons. This includes number average molecular weights of about 200 daltons, about 400 daltons, about 600 daltons, about 800 daltons, about 1,000 daltons, about 2,000 daltons, about 3,000 daltons, about 4,000 daltons, about 5,000 daltons, about 6,000 daltons, about 7,000 daltons, about 8,000 daltons, about 9,000 daltons, about 10,000 daltons, about 11,000 daltons, about 12,000 daltons, about 13,000 daltons, about 14,000 daltons, about 15,000 daltons, about 20,000 daltons, about 25,000 daltons, as well as values ​​between, inclusive, any two of these values ​​or less than any one of these values. In at least one embodiment, the chain extender may have a number average molecular weight of from about 200 to about 15,000 daltons. In at least one embodiment, the chain extender can have a number average molecular weight ranging from about 200 to about 10,000 daltons. In at least one embodiment, the chain extender can have a number average molecular weight ranging from about 200 to about 2000 daltons. Accordingly, illustrative chain extenders include, but are not limited to, PEGMMA 500, PEGMEMA 950, PEGDA 500, PEGDA 1000, PEGDA 2000, PEGDMA 300, PEGDMA 700, PEGDMA 1000, PEGDMA 2000, PPGDMA 1000, PPGDMA 2000, PEGDMA 10,000, and the like, and mixtures thereof.

[0025] In at least one embodiment, the chain extender is present in the composition at a concentration of about 0% to about 70% by weight, which may include about 1% to about 60%, about 5% to about 50%, about 10% to about 40%, about 15% to about 30%, or about 20% to about 25% of the chain extender by weight of the total weight of the composition. In various embodiments, the first and / or second solution may contain one or more chain extenders in an amount of 0%, about 1%, about 2%, about 5%, about 8%, about 10%, about 12%, about 15%, about 18%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, or a range between or less than any one of these values, inclusive of any two of these values. In an illustrative embodiment, the first solution contains from about 0% to about 40% by weight of chain extender, based on the total weight of the composition. In other embodiments, the first solution contains from about 5% to about 30% by weight of chain extender, based on the total weight of the composition.

[0026] Gelation and crosslinking of the prepolymer can occur through several mechanisms, such as chemical or physical crosslinking, including, but not limited to, free radical polymerization, condensation polymerization, complexation, hydrogen bonding, etc. In various embodiments, the organogel can further include an initiator / co-initiator pair to facilitate free radical polymerization of the prepolymer at physiological temperatures. The initiator and co-initiator are contained in separate solutions of the two-part composition. Initiators can include peroxides, hydroperoxides, and any other peroxide-containing compounds. Suitable polymerization initiators include, but are not limited to, benzoyl peroxide (BPO), cumene hydroperoxide (CHP), dicumyl peroxide (CPO), lauryl peroxide, tert-amyl hydroperoxide (t-AHP), tert-butyl hydroperoxide (t-BHP), di-tert-butyl peroxide (DTBP), tributyl hydroperoxide (TBPH), tetra-methylbutyl hydroperoxide (MBHP), and the like, and mixtures thereof.

[0027] The composition also includes a co-initiator that, when combined with the initiator, causes the prepolymer to cure at physiological temperatures. In at least one embodiment, the co-initiator can be a secondary or tertiary amine. Suitable co-initiators include, but are not limited to, N,N-dimethylaniline, triethanolamine (TEA), 1-(2-pyridyl)-2-thiourea (PTU), 1-acetyl-2-thiourea (ATU), N,N-dihydroxyethyl-p-toluidine (DHEPT), 4-(di-methylamino)phenethyl alcohol (DMAPE), 4-(dimethylamino)ethyl benzoate (EDMAB), 2-[4-(dimethylamino)phenyl]ethanol, N,N-dimethyl-p-toluidine (DMPT), bis(hydroxyethyl)-p-toluidine, and the like, and mixtures thereof.

[0028] The amount of polymerization initiator and coinitiator can be varied depending on the desired level of crosslinking and the rate of polymerization. Examples of amounts of the one or more polymerization initiators and one or more coinitiators in the total weight percent of the composition include about 0.005%, about 0.001%, about 0.01%, about 0.05%, about 0.1%, about 0.2%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 10%, about 15%, about 20%, about 25%, about 30%, and ranges between, inclusive of, or less than any one of any two of these values. In at least one embodiment, the first solution contains about 0.01% to about 3% by weight of initiator. In other embodiments, the second solution contains about 0.01% to about 3% by weight of coinitiator. In an illustrative embodiment, the first solution comprises about 0.5% to 1.5% by weight of cumene hydroperoxide. In another illustrative embodiment, the second solution comprises about 0.5% to 1.5% by weight of 1-(2-pyridyl)-2-thiourea.

[0029] In at least one embodiment, the composition of the present technology may also include a polymerization inhibitor, which may be included in one or both of the solutions of the two-part organogel formulation. The inhibitor's role is to prevent premature polymerization of the prepolymer and chain extender. The inhibitor's action may not be permanent; in exemplary embodiments, the inhibitor ensures the stability of the composition during storage. When the two components of the formulation are combined, a polymerization reaction begins, resulting in the formation of the organogel. Examples of suitable polymerization inhibitors include, but are not limited to, hydroquinone (HQ), methyl ether hydroquinone (MEHQ), butylated hydroxytoluene (BHT), 4-tert-butylpyrocatechol, tert-butylhydroquinone, 1,4-benzoquinone, 6-tert-butyl-2,4-xylenol, 2,6-di-tert-butylphenol, 1,1-diphenyl-2-picrylhydrazyl, and phenothiazine.

[0030] The inhibitor may be present in the formulation in an amount of less than 3%, less than about 1%, or less than about 0.1% by weight of the reactive components. The compositions of the present technology may further comprise one or more additives to modify or improve properties such as density, viscosity, dispensability, mechanical properties, or visual characteristics, such as illumination aids under scanning. In various embodiments, the compositions may comprise one or more additives such as fillers, contrast agents, processing aids, plasticizers, viscosity-reducing agents, high molecular weight polymers, bulking agents, stabilizers, microspheres, fibers, powders, gases, radiopaque materials, drugs, and the like. Exemplary additives include dimethyl 3,3'-thiodipropionate, sodium diatrizoate, butylene carbonate, polyurethane, collagen, polyethylene glycol, microspheres, and the like. In at least one embodiment, one or more additives may be included in the first solution, the second solution, or both solutions. In at least one embodiment, the first solution further comprises one or more additives. In at least one embodiment, the second solution further comprises one or more additives. In at least one embodiment, the one or more additives are selected from the group consisting of fillers, contrast agents, processing aids, plasticizers, and viscosity-reducing agents.

[0031] In at least one embodiment, the compositions of the present technology may further comprise one or more pharmacologically active agents in an effective amount suitable for administration to induce a desired systemic or local effect. Suitable pharmacologically active agents will be apparent to those skilled in the art and include, but are not limited to, enzymes, proteins, anti-inflammatory agents, antibiotics, antiseptics, antitumor agents, cytotoxins, antibacterial agents, antiviral agents, analgesics, growth factors, vasodilators, anesthetics, etc., or combinations thereof.

[0032] The viscosity of the first and / or second solutions of the two-part composition may optionally be modified using viscosity modifiers, emulsifiers, or miscible cosolvents to facilitate dispensing of the organogel. Suitable viscosity-modifying cosolvents include aliphatic and aromatic solvents, such as hydrocarbons, alcohols, aldehydes, amides, carbonates, ethers, esters, glycols, glycol ethers, glycol esters, ketones, sulfoxides, and other non-aqueous solvents known to those skilled in the art. Examples of such solvents include, but are not limited to, nonanol, dimethyl sulfoxide, butylene carbonate, diethylene glycol ethyl ether, dipropylene glycol methyl ether, dipropylene glycol butyl ether, tripropylene glycol methyl ether, tripropylene glycol butyl ether, and the like, or combinations thereof. In an illustrative embodiment, the composition includes nonanol as a cosolvent.

[0033] The composition may include a biocompatible contrast agent or other additive to achieve in vivo visualization and enable imaging of the device for delivery, tracking, location, and other purposes. If the composition includes a contrast agent, illustrative contrast agents include, but are not limited to, ionic and non-ionic agents such as iocarmic acid, iodipamide, iodoxamic acid, ioxaglic acid, acetolizoic acid, diatrizoic acid, iodamic acid, ioglycic acid, iopanoic acid, iopronic acid, iothalamic acid, ioxithalamic acid, ipodic acid, metrizoic acid, and pharmaceutically acceptable salts thereof, iodixanol, ioforminol, iotrolan, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, iosimide, ioversol, ioxilan, and metrizamide, and combinations thereof. In at least one embodiment, the contrast agent includes sodium diatrizoate hydrate (NaDi), sodium amidotrizoate, sodium tyropanoate, phentethiotarain sodium, calcium sodium edetate, meglumine amidotrizoate, meglumine diatrizoate, triphenylbismuth, zirconium oxide, aluminum oxide, barium sulfate, metrizamide, metrizoic acid, fenobuthiodil, lodixanol, or the like, or combinations thereof.

[0034] The composition may further comprise a viscosity-lowering agent in an amount sufficient to reduce the viscosity of the polymeric composition while maintaining suitable fluidity to facilitate its delivery to the intended application site. Suitable viscosity-lowering agents include, but are not limited to, polyethylene glycol polymers, hydrophilic, hydrophobic, or amphiphilic surfactants, organic solvents, and the like, or combinations thereof.

[0035] In various embodiments, additives and pharmacologically active agents, if present, can be incorporated into the composition at concentrations ranging from about 0.001%, about 0.01%, about 0.02%, about 0.05%, about 0.1%, about 0.5%, about 1.0%, about 2%, about 5%, about 10.0%, about 15.0%, about 20.0% by weight, as well as ranges between any two of these values ​​or less than any one of these values. For example, the composition can include about 0.1% to 10.0% by weight of the contrast agent.

[0036] In one embodiment, a composition is provided that includes two parts, the first part including a multifunctional crosslinkable prepolymer and a difunctional chain extender, a tertiary amine coinitiator, a non-aqueous solvent, and optionally a co-solvent, and the second part including a peroxide initiator, a non-aqueous solvent, and optionally a co-solvent. Suitable multifunctional crosslinkable prepolymers, difunctional chain extenders, peroxide initiators, amine coinitiators, non-aqueous solvents, and co-solvents are as described herein. In at least one embodiment, the multifunctional crosslinkable prepolymer includes ethoxylated trimethylolpropane triacrylate. In at least one embodiment, the difunctional chain extender is selected from the group consisting of polyethylene glycol monomethacrylate, polyethylene glycol dimethacrylate, polyethylene glycol methyl ether methacrylate, polypropylene glycol diacrylate, and polypropylene glycol dimethacrylate. In at least one embodiment, the non-aqueous solvent is selected from the group consisting of propylene glycol, dipropylene glycol, tripropylene glycol, tripropylene glycol methyl ether, di(ethylene glycol) ethyl ether, di(propylene glycol) butyl ether, butylene carbonate, and combinations thereof. In at least one embodiment, the co-solvent includes nonanol. In at least one embodiment, the peroxide initiator is selected from cumene hydroperoxide and benzoyl peroxide. In at least one embodiment, the tertiary amine coinitiator is selected from the group consisting of 1-(2-pyridyl)-2-thiourea, N,N-dihydroxyethyl-p-toluidine, and 1-acetyl-2-thiourea. In at least one embodiment, the composition includes a first solution including ethoxylated (20) trimethylolpropane triacrylate, polyethylene glycol dimethacrylate, 1-(2-pyridyl)-2-thiourea, and propylene glycol, and a second solution including cumene hydroperoxide and propylene glycol. In at least one embodiment, the first solution and / or the second solution further comprise a contrast agent, hi at least one embodiment, the contrast agent is sodium diatrizoate hydrate.

[0037] In various embodiments, organogels prepared using the compositions described herein are provided. In exemplary embodiments, organogels are provided, including compositions comprising two parts: a first part comprising a first solution and a second part comprising a second solution, wherein the first solution comprises a prepolymer, a non-aqueous solvent, a polymerization co-initiator, and optionally a chain extender; and the second solution comprises a polymerization initiator and a non-aqueous solvent. In various embodiments, organogels are provided, including a crosslinkable or curable prepolymer selected from ethoxylated (9) trimethylolpropane triacrylate, ethoxylated (15) trimethylolpropane triacrylate, ethoxylated (20) trimethylolpropane triacrylate (PEG-T), and propoxylated (3) trimethylolpropane triacrylate (PTMPTA) in a non-aqueous solvent, along with a redox initiator and a co-initiator pair. The organogels do not substantially swell or shrink, and the mass of the swollen organogels remains unchanged over time.

[0038] In various embodiments, organogel prepared using the methods described herein is provided. In at least one embodiment, the method includes delivering a composition comprising a first portion comprising a first solution and a second portion comprising a second solution to a site where the organogel is intended to form, contacting the first solution with the second solution, and initiating polymerization of the prepolymer to form the organogel. The first and second solutions are as described herein. In various embodiments, the first solution comprises a prepolymer, a non-aqueous solvent, a polymerization co-initiator, and optionally a chain extender, and the second solution comprises a polymerization initiator and a non-aqueous solvent. In another aspect, a method is provided for providing a system including a filling structure that can be filled with a composition adapted to polymerize to form a matrix suitable for in vivo application. The method includes delivering a filling structure that can be filled with a composition including a two-part composition described herein and initiating polymerization of the prepolymer in vivo to form an organogel. Suitable delivery protocols used to deliver the composition can include, but are not limited to, a delivery catheter having a balloon or other inflatable support for carrying the filling structure. In various embodiments, the method includes filling the filling structure with a two-part composition described herein and initiating polymerization of the prepolymer in vivo to form an organogel. In various embodiments, the filling structure is filled via a filling line.

[0039] Polymerization can be initiated by methods such as, but not limited to, free radical initiation, thermal initiation, or exposure to visible light. In at least one embodiment, polymerization can be initiated using redox radical initiated solution polymerization. Thus, in at least one embodiment, polymerization and crosslinking are initiated using a polymerization initiator and co-initiator system. Suitable prepolymers, chain extenders, solvents, initiators, and co-initiators are as described herein.

[0040] Organogels can be formed by injecting a two-part composition into an implantable device, where the composition hardens to yield a durable and biostable organogel. In one embodiment, a method for forming an organogel in situ is provided. The method includes delivering an implantable device containing the two-part composition to a site where organogel formation is intended. The composition can be delivered as a liquid, gel, foam, slurry, or the like. The composition includes a prepolymer described herein, which has a fixed shape after hardening. In at least one embodiment, the filling material can include a two-part composition system described herein. In other embodiments, the filling material can include a single composition that hardens or solidifies over time upon exposure to a physiological environment. The method for hardening or solidifying the filling material depends on the type of filling material. For example, some prepolymers can be hardened by the application of energy such as ultrasonic energy or visible light. Other prepolymers can harden when exposed to body temperature or other conditions that cause the composition to polymerize. Still other compositions are such that the components can be mixed immediately before use and hardened after a set time.

[0041] In various embodiments, each portion of the composition is initially fluid and curable or otherwise solidifiable to enable delivery to the intended site, such that once in place, the composition and the filling structure into which it is loaded or incorporated remain in place after the delivery system is removed. Certain aspects of the present technology provide compositions for intraluminal applications that are easily delivered and have stable properties.

[0042] In various embodiments, the compositions provide improved properties compared to previously known compositions, such as an improved combination of properties such as compressive strength, hardness, setting characteristics, acceptable exotherm of reaction, ease of sterilization, room temperature storage stability, biocompatibility, durability during use, and low shrink-swell. The improvements can be achieved without adversely affecting other desirable properties, including those that occur before or during delivery, during or after setting, and over the course of extended in vivo use. The properties of the final organogel can be varied, for example, by selecting appropriate specific gravities and viscosities of the first and second parts of a two-part composition. The properties of the first and / or second solutions can be varied to provide organogel with properties desired for the application. For example, the first and / or second solutions can have a high specific gravity and low viscosity for ease of delivery to the intended application site. Various embodiments relate to organogel compositions comprising the compositions. In an exemplary embodiment, provided herein is an organogel comprising a supernetwork comprising a prepolymer network comprising a prepolymer described herein, wherein the network is covalently linked by a chain extender, for example, as shown in FIG. 6.

[0043] The organogel can have a viscosity of about 100 cP or less, for example, but not limited to, about 80 cP or less, about 50 cP or less, e.g., about 45 cP or less, about 40 cP or less, about 35 cP or less, about 30 cP or less, about 25 cP or less, about 20 cP or less, or about 10 cP or less. In at least one embodiment, the viscosity of the organogel is about 5 cP to about 50 cP, e.g., about 10 cP to about 30 cP, or about 15 cP to about 25 cP, as measured in centipoise (cP) for a 30% solution at 25°C. The organogel can have a specific gravity ranging from about 0.1 to about 5, for example, but not limited to, about 0.2 to 2, about 0.3 to 1.8, about 0.5 to 1.5, or about 0.8 to 1.3. In at least one embodiment, the organogel has a specific gravity of about 0.85 to about 1.25. In at least one embodiment, the organogel generally has the same specific gravity as blood or a thrombus. The organogel can have a Shore hardness ranging from about 1 durometer to about 400 durometer, for example, but not limited to, from about 2 durometer to about 300 durometer, from about 5 durometer to about 200 durometer, from about 10 durometer to about 140 durometer, or from about 50 durometer to about 100 durometer.

[0044] When the first and second solutions of a two-part composition are mixed together, hardening can occur rapidly but through various stages as the composition progresses from a liquid to a plastic or elastomeric consistency and then to an organogel consistency. Organogel compositions are injectable solutions, and the clinically relevant time is the operating time, defined as the time it takes to inject or pump the solution through a narrow tube. The time required for the gel to harden and acquire its maximum mechanical properties is the total setting time. As a result, in at least one embodiment, the organogel has a gel set time of about 30 seconds to about 30 minutes, including gel set times of about 30 seconds to about 20 minutes, about 45 seconds to about 15 minutes, about 1 minute to about 10 minutes, and ranges therebetween, inclusive, or less than any one of any two of these values. In at least one embodiment, the organogel has a cure time of less than about 25 minutes, including cure times of less than about 20 minutes, less than about 15 minutes, or less than about 10 minutes. In at least one embodiment, the organogel has a cure time ranging from about 30 seconds to about 10 minutes, from about 1 minute to about 8 minutes, from about 3 minutes to about 5 minutes, and inclusive of any two of these values, or less than any one of these values.

[0045] The organogel of the present technology desirably exhibits low solvent loss. The volatility of the composition depends on the vapor pressure of the solvent used. In various embodiments, the organogel composition comprises at least one solvent having a vapor pressure of less than 24 mmHg at room temperature. In at least one embodiment, the organogel composition comprises at least one solvent having a vapor pressure of about 0.01 mmHg to about 23.8 mmHg, about 0.05 mmHg to about 20 mmHg, about 0.1 mmHg to about 10 mmHg, about 0.5 mmHg to about 5 mmHg, or about 0.01 mmHg to about 1.0 mmHg, and a range between, inclusive of, any two of these values, or less than any one of these values. In at least one embodiment, the organogel composition comprises at least one solvent having a vapor pressure of about 0.01 mmHg to about 1.0 mmHg.

[0046] According to embodiments of the present technology, the organogel adequately maintains its mechanical strength during and after the implantation process to maintain the implant in the desired position. Accordingly, the organogel has a static compressive modulus greater than about 0.1 MPa. This includes compressive moduli of about 0.5 MPa to about 18 MPa, about 2 MPa to about 15 MPa, about 3 MPa to about 12 MPa, about 5 MPa to about 10 MPa, and values ​​between, inclusive of, any two of these values, or less than any one of these values. In at least one embodiment, the organogel has a compressive modulus in the range of about 1 MPa to about 50 MPa, about 5 MPa to about 40 MPa, about 10 MPa to about 30 MPa, about 15 MPa to about 25 MPa, and values ​​between, inclusive of, any two of these values, or less than any one of these values. The static compressive modulus and dynamic compressive modulus refer to the ratio of stress to strain during compression under static and vibration conditions, respectively. In at least one embodiment, the composition has a static compressive modulus of about 1 MPa to about 15 MPa. In at least one embodiment, the composition has a shear modulus of about 0.5 MPa to about 2.5 MPa. In some other embodiments, the composition has a shear modulus of about 0.1 MPa to about 3 MPa.

[0047] In various embodiments, the organogels of the present technology may desirably exhibit low shrinkage-swelling properties. For example, the volume of the organogels may shrink by less than about 15%, less than about 10%, or less than about 5% after curing. In various embodiments, the organogels of the present technology may exhibit improved stability compared to other comparable compositions. For example, the modulus of the organogels changed only slightly during accelerated aging tests performed according to the stability and / or accelerated stability tests described herein. The compositions described herein may be used in implantable prostheses generally, and in particular as sealing compositions for sealing intraluminal devices to blood vessel walls or filling intraluminal filling structures such as aneurysmal sacs, which facilitate the maintenance of blood flow through the device.

[0048] In one embodiment, a method for forming an organogel is provided. The method includes delivering a composition comprising a first portion containing a first solution and a second portion containing a second solution to a site where the organogel is intended to form, contacting the first solution with the second solution, and initiating polymerization of the prepolymer to form the organogel. The first and second solutions are as described herein. In at least one embodiment of the method, the first solution can comprise one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders, while the second solution can comprise a polymerization initiator or co-initiator, a non-aqueous solvent, and optionally one or more chain extenders. In at least one embodiment of the method, the first solution, the second solution, or both solutions can further comprise one or more additives. Suitable additives are as described herein above and can be selected from the group consisting of fillers, contrast agents, processing aids, plasticizers, and viscosity-reducing agents. It will be appreciated that when the first solution contains an initiator, the second solution may contain a coinitiator, and vice versa.

[0049] In one aspect, a method of using an organogel in a system for endoluminal treatment of aneurysms is provided. In one aspect, a device is provided that includes or is filled with a composition described herein. The device can be a graft system and can include a support or scaffold. In at least one embodiment, the device includes a system for endoluminal treatment of aneurysms, including both abdominal aortic aneurysms (AAA) and thoracic aortic aneurysms (TAA). The system includes a prosthesis including a double-walled filling structure that, when filled, substantially fills the aneurysm's expanded volume and leaves the lumen in place for blood flow. In various embodiments, the system can include a prosthesis including a double-walled filling structure that, when filled, is pre-shaped or otherwise adapted to fully fill the aneurysm's expanded volume and leaves the lumen in place for blood flow. In some embodiments, fully filled can include, for example, filling sufficiently to avoid migration, support the lumen, etc. An example of such a system and method is described in US Pat. No. 8,048,145, the entire disclosure of which is incorporated herein by reference.

[0050] In one aspect, the present technology provides methods and systems for the endoluminal treatment of aneurysms, particularly aortic aneurysms, including both abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs). The systems include prostheses that include double-walled filling structures that, when filled, are pre-shaped or otherwise adapted to substantially fill or sufficiently fill the increased volume of the aneurysm, particularly a fusiform aneurysm, leaving the lumen in place for blood flow. An exemplary single prosthetic system including a filling structure mounted on a delivery catheter is shown in FIG. 1. The system 10, designed to deliver the double-walled filling structure 12 to an aneurysm, includes a delivery catheter 14 having the filling structure 12 and an expandable element 16, typically an inflatable balloon, at its distal end. The catheter 14 includes a guidewire lumen 18, a balloon inflation lumen (not shown) or other structure for expanding other expandable components, and a filling tube 20 for delivering a filling medium or material to an interior space 22 of the double-walled filling structure 12. The interior space 22 is defined between an outer wall 24 and an inner wall 26 of the filling structure 12. Upon inflation with a filling material or medium, the outer wall 24 expands radially outward, as shown by the dashed lines, as does the inner wall 26, also shown by the dashed lines. The expansion of the inner wall 26 defines an interior lumen 28. The expandable element 16, such as a balloon or other structure, is expandable and supports the interior surface of the lumen 28, as also shown by the dashed lines in FIG. 1.

[0051] The treatment system 10 of FIG. 1 can be used to treat complex morphologies of transmural abdominal aortic aneurysms (AAAs) by first positioning a delivery catheter 14 to deploy a double-walled filling structure 12 (in its unfilled state) across the aneurysm, typically from the aortic region below the renal arteries (RA) to the region beyond the iliac arteries (IA), as shown in FIG. 2 . Typically, the delivery catheter 14 is introduced over a guidewire (GW) through a patient's groin opening, accessing the iliac arteries via the Seldinger technique. After the double-walled filling structure 12 is properly positioned, an organogel-forming precursor of the present technology is introduced into the interior space 22. Filling the interior space 22 causes the outer wall 24 of the structure to expand outward, thereby conforming to the inner surface (S) of the aneurysmal space. Before, during, or after filling the double-walled filling structure 12 with an inflation medium, an expandable element 16, such as a balloon or other expandable structure, is also inflated or expanded to open the tubular lumen defined by the inner surface of the inner wall 26.

[0052] In at least one embodiment, a pair of double-walled filling structures can be used to treat an infrarenal abdominal aortic aneurysm instead of just the single filling structure illustrated in FIG. 2. A system including such a pair of filling structures is illustrated in FIG. 3, which includes a first filling structure 112 and a second filling structure 212. Each filling structure 112 and 212 is mounted on a delivery catheter 114 and 214, respectively. The components of the filling structures 112 and 212 and the delivery catheters 114 and 214 are generally the same as those previously described with respect to the single filling structure system 10 of FIG. 1, and corresponding parts of each filling system 112 and 212 are numbered the same, with either the base number 100 or the base number 200. As shown in FIG. 3, the delivery catheter 114 includes a guidewire lumen 118 and a filling tube 120. The delivery catheter 214 includes a guidewire lumen 218 and a filling tube 220. The first filling structure 112 includes an outer wall 124. Second filling structure 212 includes an outer wall 224. Outer walls 124 and 224 are expandable to allow filling of first filling structure 112 and second filling structure 212, respectively, as shown by the dashed lines. Expandable element 116, such as a balloon or other structure, is expandable to support the inner surface of lumen 128, as shown by the dashed lines in FIG. 3, and expandable element 216, such as a balloon or other structure, is expandable to support the inner surface of lumen 228, also shown by the dashed lines in FIG. 3.

[0053] On the other hand, the primary difference between the filling structures 112 and 212 of Figure 3 and the filling structure 12 of Figure 1 is that the pair of filling structures has a generally asymmetrical shape, meaning that they are positioned adjacent to each other within the aneurysm space and together fill the space. After the filling structures 112 and 212 of Figure 3 are filled with the two-part composition of the present technology, the composition cures or otherwise solidifies to form the organogel of the present technology, and the delivery catheters 114 and 214, respectively, are removed. The solidified filling structures then provide a pair of tubular lumens opening from the aorta below the renal arteries to the left and right iliac arteries. The ability of the filling structures 112 and 212 to conform to the inner surface of the aneurysm helps them remain anchored within the aneurysm with little or no migration.

[0054] In addition to the filling structure described hereinabove, the system may further include at least a first scaffold, separate from the filling structure, that is generally expandable within the tubular lumen and capable of providing blood flow after the filling structure is deployed within the aneurysm. The first scaffold is adapted to expand within at least a first portion of the tubular lumen of the filling structure and may provide one or more specific advantages. For example, the scaffold may support and smooth the inner wall of the tubular lumen, which may become uneven during solidification of the polymeric filler material. The scaffold may also provide anchoring for the filling structure at the aortic end of the graft, particularly when placed within an AAA. The scaffold may be partially or entirely covered with a membrane to form a graft. In such cases, the graft structure may serve to provide a transition from the aortic end of the blood vessel generally into the tubular lumen of the filling structure. Alternatively, the graft structure may provide one or a pair of transitions from the iliac end of the filling structure. In certain instances, the graft structure may be used on both sides of the filling structure to treat additional or consecutive aneurysmal regions in adjacent blood vessels. In at least one embodiment, the system can include multiple scaffold structures. For example, the system can include at least first and second scaffolds, one for each of the tubular lumens defined by the first and second double-walled filling structures, respectively. The scaffolds can be adapted to be arranged contiguously, often overlapping, or spaced apart at either or both ends, optionally in the region between the ends.

[0055] An example of a short, stent-like scaffold structure for a single prosthetic system is shown in Figure 4. A scaffold 60 can be implanted within the upper opening 52 of the tubular lumen of the filling structure 12 to anchor the upper end of the filling structure 12, help prevent blood from entering the area between the outer wall 24 and the inner surface (S) of the aneurysm, and generally improve the transition from the aorta into the tubular lumen. The locations of the renal arteries (RA) and iliac arteries (IA) relative to the thoracic aorta (TA) and the location of the filling structure 12 are shown in Figure 4 for one embodiment. The filling structure 12 includes an outer wall 24 and an inner wall 26, defining an interior space 22 therebetween. The tubular lumen of the filling structure 12 also has a lower end 50.

[0056] Stent-like structures for the filling structure 12 or other stent-grafts that can be used to treat aneurysms can include conventional stents, grafts, or other expandable luminal support structures known in the art. For example, a graft can include one or more circumferential inflation channels extending around the entire circumference of the graft body, or extending around a portion of the circumference of the graft body. The circumferential inflation channels can be connected to one another via longitudinal inflatable filling channels. The network of inflation channels can optionally be filled with a settable material that can solidify, harden, or otherwise be configured to increase viscosity or become more rigid after being injected into the channels. Settable inflation materials, such as gels, liquids, or other flowable materials that can set to a denser, firmer, or substantially solidified state, can be used to provide mechanical support to the graft body due to the mechanical properties of the solidified material disposed within the channels. An example of such a system and method is described in U.S. Patent Application Publication No. 2014 / 0100650, the entire disclosure of which is incorporated herein by reference. In at least one embodiment, the expandable channels may be filled with the organogel composition of the present technology.

[0057] The technology, having been broadly described above, will be more readily understood by reference to the following examples, which are provided by way of illustration and are not intended to limit the technology. [Example]

[0058] The following examples are illustrative only and are not intended to limit the scope of the other embodiments described in any way.

[0059] The following abbreviations are used in all examples: ATU: 1-acetyl-2-thiourea BPO: Benzoyl peroxide CHP: Cumene hydroperoxide DHEPT: N,N-dihydroxyethyl-p-toluidine PTU: 1-(2-pyridyl)-2-thiourea PEG-T: Ethoxylated (20) trimethylolpropane triacrylate PEGDMA 1000: Poly(ethylene glycol) dimethacrylate MW1000 PEGDMA 8000: Poly(ethylene glycol) dimethacrylate MW8000 PEGDMA 10,000: Poly(ethylene glycol) dimethacrylate MW 10,000 PEGMEMA 950: Poly(ethylene glycol) methyl ether methacrylate MW950 PEGMEMA 500: Poly(ethylene glycol) methyl ether methacrylate MW500 PEGMEMA 300: Poly(ethylene glycol) methyl ether methacrylate MW300 PEGMMA 2000: Poly(ethylene glycol) monomethacrylate MW2000 PG: Propylene glycol DPG: Dipropylene glycol TPG: Tripropylene glycol TPGME: Tripropylene glycol methyl ether DEGEE; Di(ethylene glycol) ethyl ether DPGBE: Di(propylene glycol) butyl ether BC: Butylene carbonate DMTDP: dimethyl 3,3'-thiodipropionate NaDi: sodium diatrizoate hydrate PPGDA 2000: Poly(propylene glycol) diacrylate MW2000 PPGDMA 2000: Poly(propylene glycol) dimethacrylate MW2000 HQ Hydroquinone MEHQ Methyl ether hydroquinone BHT Butylated Hydroxytoluene DMSO dimethyl sulfoxide

[0060] Example 1 Preparation of organogel Organogels were prepared by mixing two solutions, C1 and C2, together. First, C1 and C2 solutions were prepared separately by mixing the appropriate amounts of the appropriate components together until the solution was homogenous and any solids that were part of the formulation were completely dissolved. C1 was then added to C2 (or C2 was added to C1), and the two components were mixed together with constant stirring for 5–15 seconds. Alternatively, two barrel cartridges, barrel 1 and barrel 2, were filled with C1 and C2, respectively, and the solutions were mixed together while dispensing the solution into the appropriate containers through a static mixer. The final mixed solution was placed in a 37°C water bath and monitored until gelation was complete. An illustration of the formation of the organogel composition is shown in Figure 6.

[0061] [Table 1] Additional organogels are prepared using the methods described above.

[0062] [Table 2]

[0063] [Table 3]

[0064] Table 4

[0065] Table 5

[0066] Table 6

[0067] Table 7

[0068] Table 8

[0069] Table 9

[0070] Table 10

[0071] Table 11 Table 12

[0072] Table 13 Table 14

[0073] Table 15 Table 16

[0074] Table 17

[0075] Table 18 Table 19

[0076] Table 20 Table 21

[0077] Table 22

[0078] Table 23

[0079] Table 24

[0080] Table 25

[0081] [Table 26]

[0082] [Table 27]

[0083] [Table 28]

[0084] [Table 29]

[0085] Example 2 Characterization of organogel The compressive modulus of the prepared organogels was measured using a single column material testing system (Instron model number 3343) using ASTM Standard D575-91 Standard Test Method for Rubber in Compression (incorporated herein by reference). Table 1 summarizes the gel setting times and compressive moduli for the prepared organogels.

[0086] [Table 30]

[0087] Example 3 Stability testing The organogels prepared above were screened for shelf-life stability of the individual polymer system components (C1 and C2 solutions) under accelerated conditions at 60 °C for an equivalent time corresponding to 18 months at room temperature. The results showed that the individual component solutions were stable and, when combined, formed organogels suitable for the intended application. The organogel of Composition 1 was tested with an endobag (Endologix) as a component of an endovascular aneurysm repair system surrounding a stent placed within an abdominal aortic aneurysm (AAA). The endobag was prefilled and flushed with saline to remove air and determine the fill volume. After flushing, the two-component polymer system from Composition 1 was injected into the endobag using a two-barrel cartridge dispensed at 180 mmHg pressure with a ratchet gun. The endobag maintained its preset shape, thereby demonstrating the stability of the organogel.

[0088] The embodiments disclosed herein are to be considered in all respects as illustrative and not restrictive of the present invention. The present invention is in no way limited to the above-described embodiments. Various modifications and changes can be made to these embodiments without departing from the spirit and scope of the present invention. The embodiments described herein as examples may suitably be practiced without any element or elements, limitations, not specifically disclosed herein. Thus, for example, the terms "comprise," "include," "contain," and the like should be read expansively and without limitation. Furthermore, the terms and expressions used herein are used for descriptive purposes only and are not intended to be limiting. The use of such terms and expressions is not intended to exclude equivalents of the features or portions thereof shown and described, and various modifications are recognized within the scope of the present technology. Additionally, the phrase "essentially consisting of" should be understood to include the elements specifically described and additional elements that do not materially affect the basic and novel characteristics of the present technology. The phrase "consisting of" excludes any elements not specified.

[0089] The present disclosure is not limited to the particular embodiments described in this application. It will be apparent to those skilled in the art that many modifications and variations can be made without departing from the spirit and scope of the present disclosure. From the foregoing description, functionally equivalent methods and compositions within the scope of the present disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is limited only by the terms of the appended claims, including the full range of equivalents to which such claims are entitled. It is to be understood that the present disclosure is not limited to particular methods, reagents, compounds, compositions, or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0090] As will be understood by those skilled in the art, for all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges. Any recited range can readily be recognized as fully descriptive and enabling the same range broken down into at least equal ½, ⅓, ¼, ⅕, ⅙, etc. As a non-limiting example, each range set forth herein can be readily broken down into a lower ⅓, a middle ⅓, an upper ⅓, etc. As will also be understood by those skilled in the art, terms such as "up to," "at least," "greater than," "less than," and the like, all refer to ranges that are inclusive of the recited numbers and can subsequently be broken down into subranges, as described above. Finally, as will be understood by those skilled in the art, a range includes each individual member.

[0091] All publications, patent applications, issued patents, and other documents mentioned herein are incorporated by reference herein to the same extent as if each individual publication, patent application, issued patent, or other document was specifically and individually indicated to be incorporated by reference in its entirety. To the extent that any definitions contained in the text incorporated by reference conflict with definitions in the present disclosure, they are excluded.

[0092] The embodiments disclosed herein are to be considered in all respects as illustrative and not restrictive of the present invention. The present invention is in no way limited to the above-described embodiments. Various modifications and changes can be made to the embodiments without departing from the spirit and scope of the present invention. Various modifications and changes that come within the meaning and range of equivalency of the claims are intended to be within the scope of the present invention.

Claims

1. A composition comprising two parts, a first part comprising a first solution and a second part comprising a second solution, a first solution comprising one or more prepolymers, a non-aqueous solvent, a polymerization co-initiator or initiator, and optionally one or more chain extenders and additives; a second solution comprising a polymerization initiator or coinitiator, a non-aqueous solvent and optionally one or more chain extenders and additives, but no prepolymer; the polymerization initiator and the coinitiator are contained in separate solutions, a first solution and a second solution; the prepolymer is selected from the group consisting of ethoxylated (3) bisphenol A diacrylate, ethoxylated (30) bisphenol A diacrylate (EBPADA), ethoxylated (9) trimethylolpropane triacrylate, ethoxylated (15) trimethylolpropane triacrylate, ethoxylated (20) trimethylolpropane triacrylate (PEG-T), propoxylated (3) trimethylolpropane triacrylate (PTMPTA), pentaerythritol triacrylate, ethoxylated (4) pentaerythritol tetraacrylate, pentaerythritol tetraacrylate, and methacrylic variants thereof, divinyl adipate, 1,4-dibutanediol divinyl ether, di- and triethylene glycol divinyl ether, allyl ether, diallyl maleate, trimethylpropane diallyl ether, and combinations thereof; the non-aqueous solvent is selected from the group consisting of methanol, glycerin, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, tripropylene glycol, polyethylene glycol, ethyl ether, tripropylene glycol methyl ether, di(propylene glycol) butyl ether, propylene carbonate, butylene carbonate, benzene, toluene, xylene, methyl ethyl ketone, castor oil, linseed oil, sesame oil, soybean oil, olive oil, and combinations thereof; the polymerization initiator is selected from the group consisting of benzoyl peroxide (BPO), cumene hydroperoxide (CHP), dicumyl peroxide (CPO), lauryl peroxide, tert-amyl hydroperoxide (t-AHP), tert-butyl hydroperoxide (t-BHP), di-tert-butyl peroxide (DTBP), tributyl hydroperoxide (TBPH), tetra-methylbutyl hydroperoxide (MBHP), and combinations thereof; the polymerization co-initiator is selected from the group consisting of triethanolamine (TEA), 1-(2-pyridyl)-2-thiourea (PTU), 1-acetyl-2-thiourea (ATU), N,N-dihydroxyethyl-p-toluidine (DHEPT), 4-(di-methylamino)phenethyl alcohol (DMAPE), 4-(dimethylamino)ethyl benzoate (EDMAB), 2-[4-(dimethylamino)phenyl]ethanol, N,N-dimethyl-p-toluidine (DMPT), bis(hydroxyethyl)-p-toluidine, and combinations thereof; A composition for an intraluminal device, the composition comprising 25 to 80% by weight of a non-aqueous solvent.

2. The composition of claim 1 , wherein the chain extender comprises a mono- or di-functional compound having acrylate, methacrylate, or vinyl functionality.

3. 3. The composition of claim 2, wherein the chain extender is selected from the group consisting of polyethylene glycol monoacrylate (PEGMA), polypropylene glycol monoacrylate (PPGMA), polyethylene glycol diacrylate (PEGDA), polypropylene glycol diacrylate (PPGDA), dipropylene glycol diacrylate (DPGDA), tetraethylene glycol diacrylate (TEGDA), tripropylene glycol diacrylate (TPGDA), polyethylene glycol monomethacrylate (PEGMMA), polypropylene glycol monomethacrylate (PPGMMA), polyethylene glycol methyl ether methacrylate (PEGMEMA), polyethylene glycol dimethacrylate (PEGDMA), polypropylene glycol dimethacrylate (PPGDMA), and combinations thereof.

4. The composition of claim 1 , wherein either or both of the first and second solutions further comprise a co-solvent.

5. 5. The composition of claim 4, wherein the co-solvent is selected from the group consisting of nonanol, dimethyl sulfoxide, butylene carbonate, diethylene glycol ethyl ether, dipropylene glycol methyl ether, dipropylene glycol butyl ether, tripropylene glycol methyl ether, and tripropylene glycol butyl ether, and combinations thereof.

6. The composition of claim 1 further comprising one or more additives.

7. 7. The composition of claim 6, wherein the one or more additives are selected from the group consisting of fillers, contrast agents, processing aids, plasticizers, and viscosity reducers.

8. 10. An organogel for an intraluminal device comprising the composition of claim 1.

9. 10. A system for treating an aneurysm comprising a filling structure filled with the composition of claim 1.

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