vaso-occlusive device for body cavities

专利摘要:
EMBOLIC DEVICE WITH FORMATTED WIRE. Devices for the occlusion of body cavities, such as embolization of vascular aneurysms and the like, and methods for making and using such devices. The devices can be comprised of new expandable materials, new infrastructure design, or both. The devices provided are very flexible and allow deployment with little or no damage to body tissues, conduits, cavities, etc.
公开号:BR112014012567B1
申请号:R112014012567-8
申请日:2012-11-21
公开日:2020-10-20
发明作者:Heath Bowman
申请人:Microvention, Inc；
IPC主号:

专利说明:

RELATED REQUESTS
[001] This order claims priority for U.S. Provisional Order No. 61 / 563,400 filed on November 23, 2011, entitled Embolic Device with Shaped Wire, and U.S. Provisional Order No. 61 / 669,645, filed on July 9, 2012, entitled Embolic Device with Shaped Wire, both of which are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION
[002] Occlusion of body cavities, blood vessels, and other lumens by embolization, is desired in a number of clinical situations. For example, occlusion of the fallopian tubes for sterilization purposes, and occlusive repair of heart defects, such as a patent foramen ovale, patent artery canal, and left atrial appendage, and atrial septal defects. The function of an occlusion device in such situations is to substantially block or inhibit the flow of body fluids within or through the cavity, lumen, vessel, space or defect for the patient's therapeutic benefit.
[003] Blood vessel embolization is also desired in a number of clinical situations. For example, vascular embolization has been used to control vascular bleeding, to occlude the blood supply to tumors, and to occlude vascular aneurysms, particularly intracranial aneurysms. In recent years, vascular embolization for the treatment of aneurysms has received much attention. Several different treatment modalities have been shown in the prior art. One approach that has shown promise is the use of thrombogenic microspirals. These microspirals can be made of biocompatible metal alloy (s) (typically a radiopaque material such as platinum or tungsten) or a suitable polymer. Examples of microspirals are described in the following patents: U.S. Patent No. 4,994,069 - Ritchart and others; U.S. Patent No. 5,133,731 - Butler et al; U.S. Patent No. 5,226,911 - Chee and others; U.S. Patent No. 5,312,415 - Palermo; U.S. Patent No. 5,382,259 - Phelps and others; U.S. Patent No. 5,382,260 - Dormandy, Jr. and others; U.S. Patent No. 5,476,472 - Dormandy, Jr. and others; U.S. Patent No. 5,578,074 - Mirigian; U.S. Patent No. 5,582,619 - Ken; U.S. Patent No. 5,624,461 - Mariant; U.S. Patent No. 5,654,558 - Horton; U.S. Patent No. 5,658,308 - Snyder; and U.S. Patent No. 5,718,711 - Berenstein and others; all of which are incorporated herein by reference.
[004] A specific type of microspiral that has achieved a measure of success is the Guglielmi Detachable Coil ("GDC"), described in U.S. Patent No. 5,122,136 - Guglielmi et al. GDC employs a platinum wire spiral fixed to a stainless steel distribution wire by a solder connection. After the spiral is placed inside an aneurysm, an electric current is applied to the distribution wire, which electrolytically disintegrates the weld joint, thereby separating the spiral from the distribution wire. The application of current also creates a positive electrical charge in the spiral, which attracts negatively charged blood cells, platelets, and fibrinogen, thereby increasing the spiral's thrombogenicity. Several spirals of different diameters and lengths can be packed into an aneurysm until the aneurysm is completely filled. The spirals thus create and maintain a thrombus within the aneurysm, inhibiting its displacement and fragmentation.
[005] A more recent development in the field of microspiral vaso-occlusive device is exemplified in U.S. Patent No. 6,299,629 to Greene, Jr. et al., U.S. Patent No. 6,602,261 to Greene, Jr et al., And U.S. co-pending Patent Application No. 10 / 631,981 to Martinez; all assigned to the assignee of the present invention and incorporated herein by reference. These patents describe vaso-occlusive devices comprising a microspiral with one or more expandable elements arranged on the outer surface of the spiral. The expandable elements can be formed from any of a number of expandable polymer hydrogels, or alternatively, environmentally sensitive polymers that expand in response to a change in an environmental parameter (eg temperature or pH) when exposed to a physiological environment, such as bloodstream. SUMMARY OF THE INVENTION
[006] The present invention is directed to new vaso-occlusive devices comprising a transport element, one or more new expandable elements, and a combination thereof. In general, the expandable element or elements comprise an expandable polymer. The transport element can be used to assist the distribution of the expandable element by providing a structure that, in some embodiments, allows coupling to a delivery mechanism and, in some embodiments, improves the radiopacity of the device.
[007] In one embodiment, the transport element may have a cross-sectional shape, not round. For example, the wire of the transport element may be oval, half circle, half double D oval, or arc shaped.
[008] In one embodiment, the expandable polymer is an environmentally sensitive polymer hydrogel, such as that described in U.S. Patent No. 6,878,384, issued on April 12, 2005 to Cruise et al., Incorporated herein by reference. In another embodiment, the expandable polymer is a new hydrogel comprised of sodium acrylate and a derivative of poly (ethylene glycol). In another embodiment, the expandable polymer is a hydrogel comprising a Pluronics® derivative.
[009] In one embodiment, the expandable polymer is a new hydrogel that has ionizable functional groups and is made up of macromers. Macromers can be non-ionic and / or unsaturated with ethylene.
[010] In one embodiment, macromers can have a molecular weight of about 400 to about 35,000 grams / mol. In another embodiment, macromers can have a molecular weight of about 5,000 to about 15,000 grams / mol. In yet another embodiment, macromers can have a molecular weight of about 7,500 to about 12,000 grams / mol. In one embodiment, macromers have a molecular weight of 8,000 grams / mol.
[011] In one embodiment, the hydrogel can be made of polyethers, polyurethane, derivatives thereof, or combinations thereof. In another embodiment, ionizable functional groups may comprise basic groups (for example, amines, derivatives thereof or a combination thereof) or acid groups (for example, carboxylic acids, derivatives thereof or combinations thereof). If the ionizable functional groups comprise basic groups, the basic groups can be deprotonated at pHs greater than pKa or protonated at pH less than pKa of the basic groups. If the ionizable functional groups comprise acidic groups, the acidic groups can be protonated at pHs less than pKa or deprotonated at pHs greater than pKa of acidic groups.
[012] In one embodiment, macromers may comprise vinyl, acrylate, acrylamide, or poly (ethylene glycol) methacrylate derivatives, or combinations thereof. In another embodiment, the macromer can comprise poly (elylene glycol) di-acrylamide. In another embodiment, the hydrogel is substantially free, more preferably free of unbound acrylamide.
[013] In one embodiment, macromers can be cross-linked with a compound that contains at least two fractions not saturated with ethylene. Examples of compounds unsaturated with ethylene include N, N'-methylenebisacrylamide, derivatives thereof, or combinations thereof. In another embodiment, the hydrogel can be prepared using a polymerization initiator. Examples of suitable polymerization initiators include N, N, N ', N'-tetramethylethylenediamine, ammonium peroxide, azobisisobutyronitrile, benzoyl peroxides, derivatives of the same or combinations thereof. The polymerization initiator can be soluble in aqueous or organic solvents. For example, azobisisobutyronitrile is not soluble in water; however, water-soluble derivatives of azobisisobutyronitrile, such as 2,2'-azobis (2-methylproprionamide) dihydrochloride, are available. In another fashion, the hydrogel can be substantially non-resorbable, non-degradable or both, under physiological conditions.
[014] In one embodiment, the invention comprises a method for preparing an environmentally sensitive hydrogel for implantation in an animal. The method includes combining at least one, preferably non-ionic, macromer with at least one ethylenically unsaturated fraction, at least one macromer or monomer having at least one ionizable functional group and at least one ethylenically unsaturated fraction , at least one polymerization initiator, and at least one solvent to form a hydrogel. The solvent can include aqueous or organic solvents, or combinations thereof. In another embodiment, the solvent is water. Next, the hydrogel can be treated to prepare an environmentally sensitive hydrogel, preferably one that is responsive to physiological conditions. The ionizable functional group (s) can be an acid group (for example, a carboxylic acid, a derivative thereof, or combinations thereof) or a basic group (for example, an amine, derivatives thereof, or combinations thereof). If the ionizable functional group comprises an acidic group, the treatment step may comprise incubating the hydro-gel in an acidic environment to protonate the acidic groups. If the ionizable functional group comprises a basic group, the treatment step may comprise including the hydrogel in a basic environment to deprotonate the basic groups. In certain embodiments, it is preferable that the acid groups are able to be deprotonated, or conversely, the basic groups are able to be protonated after implantation in an animal.
[015] In one embodiment, the macromer unsaturated with ethylene may have a group of vinyl, acrylate, methacrylate, or acrylamide; including derivatives thereof or combinations thereof. In another modality, the ethylenically unsaturated macromer is based on poly (ethylene glycol), derivatives thereof or combinations thereof. In another embodiment, the ethylenically unsaturated macromer is poly (ethylene glycol) di-acrylamide, poly (ethylene glycol) di-acrylate, poly (ethylene glycol) di-methacrylate, derivatives thereof, and combinations thereof. In another embodiment, the ethylenically unsaturated macromer can be used in a concentration of about 5% to about 40% by weight, more preferably about 30% to about 30% by weight. The solvent can be used in a concentration of about 20% to about 80% by weight.
[016] In one embodiment, the combination step also includes adding at least one cross-linking agent comprising an ethylenically unsaturated compound. In certain embodiments of the present invention, a cross-linking agent may not be necessary. In other words, the hydrogel can be prepared using a macromer with several unsaturated ethylene fractions. In another modality, the polymerization initiator can be a reduction-oxidation polymerization initiate. In another embodiment, the polymerization initiator can be N, N, N ', N'-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2'-azobis (2-methylproprionamide) dihydrochloride, derivatives thereof or their combinations. In another modality, the combination step also includes adding a porosigen.
[017] In one embodiment, the ethylenically unsaturated macromer includes poly (ethylene glycol) di-acrylamide, the macromer or monomer or polymer with at least one ionizable group and at least one ethylenically unsaturated group includes sodium acrylate, the initiator of polymerization includes ammonium persulfate and N, N, N ', N'-tetramethylethylenediamine, and the solvent includes water.
[018] In one embodiment, the ethylenically unsaturated macromer has a molecular weight of about 400 to about 35,000 grams / mol. In another fashion, the ethylenically unsaturated macromer has a molecular weight of about 5,000 to about 15,000 grams / mol. In one embodiment, ethylenically unsaturated macromer has a molecular weight of about 7,500 to about 12,000 grams / mol. In another embodiment, the environmentally sensitive hydrogel is substantially non-resorbable, or non-degradable or both under physiological conditions. In certain embodiments, the environmentally sensitive hydrogel can be substantially free or completely free of unbound acrylamide.
[019] In one embodiment, the transport element comprises a spiral or microspiral made of metal, plastic or similar materials. In another mode, the transport element comprises a braid or mesh made of metal, plastic or similar materials. In another embodiment, the transport element comprises a plastic or metal tube with multiple cuts or slits cut into the tube.
[020] In one embodiment, the expandable element is generally coaxially arranged within the transport element. In another embodiment, a stretch-resistant element is arranged parallel to the expandable element. In another embodiment, the stretch-resistant element is rolled, tied or twisted around the expandable element. In another embodiment, the stretch-resistant element is positioned within the expandable element. In another embodiment, the stretch-resistant element is located inside or partially surrounded by the expandable element.
[021] In one embodiment, the device comprising the expandable element and the transport element, is detachably coupled in a distribution system. In another embodiment, the device is configured for delivery by in-pumping or injecting through a conduit into a body.
[022] In one embodiment, the expandable element is environmentally sensitive and exhibits delayed expansion when exposed to body fluids. In another mode, the expandable element expands rapidly in contact with a body fluid. In another embodiment, the expandable element comprises a porous or cross-linked structure that can form a surface or framework for cell growth.
[023] In one embodiment, the expandable element expands in a dimension that is larger than the diameter of the transport element in order to provide increased filling of the lesion. In another embodiment, the expandable element expands to a size equal to or less than the diameter of the transport element to provide a framework for cell growth, release of therapeutic agents such as pharmaceuticals, proteins, genes, biological compounds such as fibrofin, or the like. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view showing an embodiment of the present invention before the expansion of the expandable element. Figure 2 is a perspective view showing a device similar to Figure 1, in an expanded state. Figure 3 is a perspective view of an alternative embodiment of the present invention. Figure 4 is a perspective view of an alternative embodiment in which the transport element comprises a fenestrated tube, braid or mesh. Figure 5 is a perspective view of an alternative embodiment incorporating a stretch-resistant element moving approximately parallel to the expandable element. Figure 6 is a perspective view of an alternative embodiment incorporating a stretch-resistant element approximately interlaced with the expandable element. Figure 7 is a perspective view of an alternative embodiment in which the expandable element has formed a loop or fold outside the transport element. Figure 8 is a perspective view of an alternative modality showing a device similar to the one shown in Figure 1 and Figure 2, in which the expandable element is not expanded to a larger diameter than the transport element. Figure 9 is a side view of an embodiment showing a device similar to that shown in Figure 1 and Figure 2. Figure 10 is an exploded perspective view of the device in Figure 9. Figure 11 is a side view of the device in Figure 9 connected to a distribution device. Figure 12 is a side view of a preferred embodiment of an implant according to the present invention. Figure 13 is a side view of a preferred embodiment of an implant according to the present invention. Figure 14 is a cross-sectional view of a transport element according to the present invention. Figure 15 is a cross-sectional view of a transport element according to the present invention. Figure 16 is a cross-sectional view of a transport element according to the present invention. Figure 17 is a cross-sectional view of a transport element according to the present invention. Figure 18 is a cross-sectional view of a transport element of Figure 14 according to the present invention. Figure 19 is a side view of a transport element according to the present invention. Figure 20 is a side view of a transport element according to the present invention. Figure 21 is a side view of a transport element according to the present invention. Figures 22-24 are side views of a transport element according to an alternative embodiment of the present invention. DETAILED DESCRIPTION
[024] As used here, the term "macromer" refers to a large molecule containing at least one active polymerization site or agglutination site. Macromers have a higher molecular weight than monomers. For example, an acrylamide monomer has a molecular weight of about 71.08 grams / mol while a poly (ethylene glycol) di-acrylamide macromer can have a molecular weight of about 400 grams / mol or greater . Preferred macromers are non-ionic, that is, they are not charged at all pHs.
[025] As used here, the term "environmentally sensitive" refers to a material (for example, a hydrogel) that is sensitive to changes in the environment including, but not limited to, pH, temperature and pressure. Many of the expandable materials suitable for use in the present invention are environmentally sensitive under physiological conditions.
[026] As used here, the term "non-resorbable" refers to a material (for example, a hydrogel) that cannot be easily and / or substantially degraded and / or absorbed by body tissues.
[027] As used here, the term "unexpanded" refers to the state in which a hydrogel is substantially unhydrated and, therefore, unexpanded.
[028] As used here, the term "ethylenically unsaturated" refers to a chemical entity (for example, a macromer, monomer or polymer) containing at least one carbon-carbon double bond.
[029] Referring to Figures 1-8, the device comprises an expandable element 1 and a transport element 2. The expandable element 1 can be made from a variety of suitable biocompatible polymers. In one embodiment, the expandable element 1 is made of a bioabsorbable or biodegradable polymer, such as those described in U.S. Patent No. 7,070,607 and 6,684,884, descriptions of which are incorporated herein by reference. In another embodiment, the expandable element 1 is made of a soft-shaped material and more preferably an expandable material such as hydrogel.
[030] In one embodiment, the material forming the expandable element 1 is an environmentally sensitive hydrogel, such as that described in U.S. Patent No. 6,878,384, the description of which is incorporated herein by reference. Specifically, the hydrogels described in U.S. Patent No. 6,878,384 are of a type that undergo controlled ex-volumetric expansion in response to changes in such environmental parameters as pH or temperature. These hydrogels are prepared by forming a liquid mixture that contains (a) at least one monomer and / or polymer, at least part of which is sensitive to changes in an environmental parameter; (b) a cross-linking agent; and (c) a polymerization initiator. If desired, a porosigen (eg, NaCl, ice crystals, or sucrose) can be added to the mixture, and then removed from the resulting solid hydrogel to provide a hydrogel with sufficient porosity to allow for cell growth. The controlled expansion rate is provided by incorporating ethylenically unsaturated monomers with ionizable functional groups (eg, amines, carboxylic acids). For example, if acrylic acid is incorporated into the reticulated network, the hydrogel is incubated in a low pH solution to protonate the carboxylic acid groups. After the excess of the low pH solution is washed and the hydrogel is dried, the hydrogel can be introduced through a microcatheter filled with saline solution at physiological pH or with blood. The hydrogel cannot expand until the carboxylic acid groups deprotonate. Conversely, if an amine-containing monomer is incorporated into the cross-linked network, the hydrogel is incubated in a high pH solution to deprotonate the amines. After the excess of high pH solution is washed and the hydrogel is dried, the hydrogel can be introduced through a microcatheter filled with saline solution at physiological pH or with blood. The hydrogel cannot be expanded until the amine groups protonate.
[031] In another embodiment, the material forming the expandable element 1 can be an environmentally sensitive hydrogel, similar to those described in U.S. Patent No. 6,878,384; however, an ethylenically unsaturated, preferably non-ionic macromer replaces or increases at least one monomer or polymer. Applicants have surprisingly found that hydrogels prepared according to this modality can be softer and / or more flexible in their unexpanded state than those prepared according to U.S. Patent No. 6,878,384. Applicants have also found that ethylenically unsaturated and non-ionic macromers (for example, poly (ethylene glycol) and derivatives thereof) can be used not only to prepare a more flexible non-expanded hydrogel; but in combination with monomers and polymers containing ionizable groups, one that can also be treated to be environmentally sensitive. The surprising increase in unexpanded flexibility allows hydrogels, for example, to be more easily deployed on an animal or deployed with little or no damage to body tissues, conduits, cavities, etc.
[032] Hydrogels prepared from non-ionic macromers in combination with monomers and polymers with non-ionizable functional groups are still capable of undergoing controlled volumetric expansion in response to changes in environmental parameters. These hydrogels can be prepared by combining in the presence of a solvent: (a) in at least one macromer, preferably non-ionic, with several ethylenically unsaturated fractions; (b) a macromer or polymer or monomer having at least one ionizable functional group and at least an ethylenically unsaturated fraction; and (c) a polymerization initiator. It is worth noting that with this type of hydrogel, a crosslinking agent may not be necessary for crosslinking since, in certain embodiments, the selected components may be sufficient to form the hydrogel. As previously described here, a porosigen can be added to the mixture and then removed from the resulting hi-drogel to provide a hydrogel with sufficient porosity to allow for cell growth.
[033] The expansion rate of hydrogels containing nonionic macromer can be provided by incorporating at least one macromer or polymer or monomer having at least one ionizable functional group (eg, amine, carboxylic acid). As discussed above, if the functional group is an acid, the hydrogel is incubated in a low pH solution to protonate the group. After the excess of low pH solution is washed and the hydrogel is dried, the hydrogel can be introduced into a microcatheter, preferably filled with saline. The hydrogel cannot expand until the acid group (s) deprotone. Conversely, if the functional group is an amine, the hydrogel is incubated in a high pH solution to deprotonate the group. After the excess of high pH solution is washed and the hydrogel is dried, the hydrogel can be introduced through a microcatheter, preferably filled with saline. The hydrogel cannot expand until the protone amine (s).
[034] More specifically, in one embodiment, the hydrogel is prepared by combining at least one nonionic macromer having at least one unsaturated fraction, at least one macromer or monomer or polymer having at least one ionizable functional group and at least one ethylenically unsaturated fraction, at least one polymerization initiator, and a solvent. Optionally, an ethylenically unsaturated crosslinking agent and / or porosigen can also be incorporated. In one embodiment, concentrations of nonionic macromers in the solvent range from about 5% to about 60% (w / w). In another embodiment, concentrations of non-ionic macromers in the solvent range from about 20% to about 30% (w / w). In one embodiment, concentrations of non-ionic macromers in the solvent is about 35% (w / w). In one embodiment, the nonionic macromer is poly (ethylene glycol), its derivatives and combinations. Derivatives include, but are not limited to, poly (ethylene glycol) di-acrylamide, poly (ethylene glycol) di-acrylate, and poly (ethylene glycol) dimethacrylate. Poly (ethylene glycol) di-acrylamide is a preferred derivative of poly (ethylene glycol) and has a molecular weight ranging from about 8,500 grams / mol to about 12,000 grams / mol. The macromer can have less than 20 polymerization sites, and more preferably about two to four polymerization sites. Poly (ethylene glycol) di-acrylamide has two polymerization sites.
[035] Preferred macromers or polymers or monomers having at least one ionizable functional group include, but are not limited to compounds having fractions of carboxylic acid or amine or, derivatives thereof, or combinations thereof. Sodium acrylate is a compound containing the preferred ionizable functional group and has a molecular weight of 94.04 g / mol. In one embodiment, concentrations of macromers or polymers or ionizable monomers in the solvent range from about 5% to about 60% (w / w). In another embodiment, the concentrations of macromers or polymers or monomers in the solvent vary from about 20% to about 30% (w / w). in one embodiment, concentrations of macromers or polymers or monomers in the solvent are about 27% (w / w). In some embodiments, at least about 10% -30% of the selected macromers or polymers or monomers must be sensitive to pH. In one embodiment, no free acrylamide is used in the macromer containing hydrogels of the present invention.
[036] When used, the crosslinking agent can be any multifunctional ethylenically unsaturated compound, preferably N, N'-methylenebisacrylamide. If biodegradation of the hydrogel material is desired, a biodegradable crosslinking agent can be selected. The concentrations of the crosslinking agent in the solvent should be less than about 1% w / w, and preferably less than about 0.1% (w / w).
[037] As described above, if a solvent is added, it can be selected based on the solubilities of the macromer (s) or monomer (s) or polymer (s), crosslinking agent, and / or porosigen used. If a liquid macromer or monomer or polymer solution is used, a solvent may not be necessary. A preferred solvent is water, but a variety of aqueous or organic solvents can be used. In one embodiment, solvent concentrations range from about 20% to about 80% (w / w). In another embodiment, solvent concentrations range from about 40% to about 60% (w / w).
[038] Density of crosslinking can be manipulated through changes in the concentration of macromer or monomer or polymer, molecular weight of the macronomer, concentration of solvent and, when used, concentration of crosslinking agent. As described above, the hydrogel can be cross-linked by means of reduction-oxidation, radiation, and / or heat. A preferred type of polymerization initiator is one that acts by reducing oxidation. Suitable polymerization initiators include, but are not limited to, N, N, N ', N'-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2'-azobis (2-methylproprionamide) dihydrochloride, derivatives thereof or their combinations. A combination of ammonium persulfate and N, N, N ', N'-tetramethylethylenediamine is a preferred polymerization initiator for use in the embodiments of the invention containing the macromer.
[039] After the polymerization is complete, the hydrogels of the present invention can be washed with water, alcohol or other suitable washing solution (s) to remove any porosigen (s), any macromer (s), monomer (s) ) and residual polymer (s) and any unincorporated oligomers. Preferably, it is carried out by initially washing the hydrogel in distilled water.
[040] Porosity can be conferred on the solid hydrogel through the use of poligens such as sodium chloride, ice crystals, or sucrose. Polymerization of the monomer solution around the suspended solid particles and subsequent removal of the solid particles from the hydrogel can provide a hydrogel with sufficient porosity to allow cell growth. A preferred porosigen is sodium chloride with particles smaller than 10 microns in diameter. Preferred concentrations of sodium chloride in the monomer solution range from 0.2 to 0.4 g of sodium chloride per g of monomer solution.
[041] The hydrogels of the present invention can be made environmentally sensitive by protonating and deprotonating the ionizable functional groups present in the hydrogel network, as discussed above. Once the hydrogel has been prepared and, if necessary, washed, the hydrogel can be treated to make the hydrogel environmentally sensitive. For hydrogel networks where the ionizable functional groups are carboxylic acid groups, the hydrogel is incubated in a low pH solution. The free protons in the solution defile the carboxylic acid groups in the hydrogel network. The duration and temperature of the incubation and the pH of the solution influence the amount of control in the rate of expansion. In general, the duration and temperature of the incubation are directly proportional to the amount of expansion control, while the pH of the incubation solution is inversely proportional to it.
[042] It has been determined that the water content in the incubation solution also affects expansion control. In this respect, the larger water content allows for greater hydrogel expansion and is thought to increase the number of carboxylic acid groups accessible to protonation. Optimization of water content and pH is required for maximum expansion rate control. Expansion control, among other things, has an effect on device positioning / repositioning time.
[043] After incubation, the excess of the treatment solution is washed off and the hydrogel material is dried. A hydrogel treated with the low pH solution was observed to dry to a smaller size than an untreated hydrogel. This effect is desirable since devices containing these hydrogels can be delivered via a microcatheter.
[044] For hydrogel networks where the ionizable functional groups are amine groups, the hydrogel is incubated in a high pH solution. Unlike functional groups of carboxylic acid, deprotonation occurs in the amine groups of the hydrogel network at high pH. In addition to the pH of the incubation solution, the incubation is carried out similarly to that of the carboxylic acid containing hydrogels. In other words, the duration and temperature of the incubation and the pH of the solution are directly proportional to the amount of expansion control. After the incubation is complete, the excess treatment solution is washed off and the hydrogel material is dried.
[045] In a preferred embodiment, the expandable element 1 is an expandable hydrogel comprised of (a) at least one macromer or preferably nonionic, ethylenically unsaturated macromer or polymer having at least two crosslinkable groups; (b) at least one monomer and / or polymer that has at least one crosslinkable group, and at least a fraction that is sensitive to changes in an environmental parameter; and (c) a polymerization initiator. In some embodiments, monomers and polymers may be soluble in water, while in other embodiments they may be non-soluble in water. Polymers suitable for component (a) include poly (ethylene glycol), poly (ethylene oxide), polyvinyl alcohol, polypropylene oxide, poly (propylene glycol), poly (ethylene oxide) - co-poly (propylene oxide) poly (vinyl pyrrolidone), poly (amino acids), dextrans, poly (ethyloxazoline), polysaccharides, proteins, glycosaminoglycans and carbohydrates and derivatives thereof. The preferred polymer is poly (ethylene glycol) (PEG), especially for component (a). Alternatively, polymers that partially or completely biodegrade can be used.
[046] One embodiment comprises combining in the presence of a solvent (a) about 5% to about 50% of a macromer or monomer or ethylenically unsaturated, non-ionic polymer; (b) about 5% to about 60% of a monomer or ethylenically unsaturated polymer with at least one ionizable functional group; and (c) a polymerization initiator. Suitable ionizable ethylenically unsaturated monomers include acrylic acid and methacrylic acid, as well as their derivatives. A suitable monomer having at least one ionizable functional group is sodium acrylate. Suitable macromers with two ethylenically unsaturated fractions include poly (ethylene glycol) di-acrylate and poly (ethylene glycol) di-acrylamide, and poly (ethylene glycol) di-acrylamide, which have molecular weights ranging between 400 and 30,000 grams / mol. The use of macromers with various ethylenically unsaturated groups allows the elimination of the crosslinking element, as the crosslinking agent functions are performed by the multifunctional polymer. In one embodiment, the hydrogel comprises about 5% to about 60% sodium acrylate, about 5% to about 50% poly (ethylene glycol) di-acrylamide.
[047] A sodium acrylate / poly (ethylene glycol) di-acrylamide hydrogel is used to improve the mechanical properties of the environmentally sensitive hydrogel previously described. As a sodium acrylate / poly (ethylene glycol) di-acrylamide hydrogel is softer than a sodium acrylate / acrylamide hydrogel (for example one used in MicroVention Hydrogel Embolic System (HES) made by MicroVention , Aliso Viejo, CA), devices that incorporate it may be more flexible. Due to the relative stiffness of the HES, MicroVention recommends pre-softening the device by immersing it in hot fluid or vaporizing the implant. In addition, devices made of acrylamide are relatively straight before pre-softening because the rigidity of the acrylamide-based hydrogel prevents the transport element (for HES, a microspiral) from assuming its secondary configuration. Devices made of a sodium acrylate / poly (ethylene glycol) di-acrylamide hydrogel may not require pre-softening techniques such as dipping in hot fluid such as saline or blood or exposing to steam in order to form in a secondary configuration heat-hardened in the transport element 2 or a similar transport element. Thus, in embodiments comprising, for example, sodium acrylate and poly (ethylene glycol) di-acrylamide, a substantially continuous length of hydrogel disposed both within lumen 3 of the transport element 2 as shown, for example, in Figure 1, as well as in a transport element, such as those shown in order '981 by Martinez or' 261 by Gre-ene, will form in the secondary configuration preformed in the transport element without pre-treatment (for example, exposure to steam , fluid or blood). This makes the device easier to use because it allows for the elimination of the pretreatment step and the device can be safer when implanted in the patient because a softer device is less likely to cause damage to the injury. Examples
[048] 3 g of acrylamide, 1.7 g of acrylic acid, 9 mg of bisacrylamide, 50 mg of N, N, N ', N'-tetramethylethylenediamine, 15 mg of ammonium persulfate, and 15.9 g of water were combined and polymerized in a 0.508 mm tube. The tube polymer was removed from the tubing to prepare Hydrogel 1 according to U.S. Patent No. 6,878,384.
[049] 4.6 g of poly (ethylene glycol) diacrylamide, 3.3 g of sodium acrylate, 100 mg of N, N, N ', N'-tetramethylethylenediamine, 25 mg of ammonium persulfate, and 15.9 g of water were combined and polymerized in a 0.50 mm tube. The tube polymer was removed from the tubing to prepare Hydrogel 2 according to a macromer-containing hydrogel embodiment of the present invention.
[050] A large platinum microspiral for the above examples has an external diameter of 0.355 mm and a 0.063 mm filar. A small platinum microspiral has an outer diameter of 0.254 mm and a 0.050 mm strand.
[051] 8.3 g of poly (ethylene glycol) diacrylamide, 9.0 of sodium acrylate, 155 mg of N, N, N ', N'-tetramethylethylenediamine, 20 mg of ammonium persulfate, and 15.9 g of water were combined and polymerized in a 0.635 mm tube. The tube polymer was removed from the tubing to prepare Hydrogel 3 in accordance with a macromer-containing hydrogel embodiment of the present invention.
[052] Hydrogel 3 is different from the examples of Hydrogel 1 and 2. Hydrogel 3 has reduced rigidity in relation to Hydrogel 1 and does not require pre-treatment before use. Such pre-treatment may sometimes require immersion in hot fluid or vaporization to obtain the desired flexibility. Hydrogel 3 also allows for increased expansion compared to Hydrogel 2.
[053] In another embodiment, monomers are used to impart fractions in the expandable element 1 that are suitable for coupling bioactive compounds, for example, anti-inflammatory agents such as corticosteroids (for example prednisone and dexamethasone); or vasodilators such as nitrous oxide or hydralazine; or anti-thrombotic agents such as aspirin and heparin; or other therapeutic compounds, proteins such as mussel adhesive proteins (MAPs), amino acids such as 3- (3,4-dihydroxyphenyl) -L-alanine (DOPA), genes or cellular material; see U.S. Patent 5,658,308, WO 99/65401, Polymer Preprints 2001, 42 (2), 147 Synthesis and Characterization of Self-Assembling Block Copolymers Containg Adhesive Moilings by Kui Hwang et al., and WO 00/27445; descriptions of which are incorporated herein by reference. Examples of fractions for incorporation into hydrogel materials include, but are not limited to, hydroxyl groups, amines and carboxylic acids.
[054] In another embodiment, the expandable element 1 can become radiopaque by incorporating monomers and / or polymers containing, for example, iodine, or by incorporating radiopaque metals such as tantalum and platinum.
[055] In some embodiments, the transport element 2 is an elongated, flexible structure. Suitable configurations for transport element 2 include helical spirals, braids and tubes with slits or spiral cut. The transport element 2 can be made of any biocompatible metal or polymer such as platinum, tungsten, PET, PEEK, Teflon, Nitinol, Nylon, steel, and the like. The conveying element can be formed in a secondary configuration such as propeller, box, sphere, flat rings, J shape, S shape or other complex shape known in the art. Examples of suitable formats are described in Horton 5,766,219; Schaefer Appl No. 10 / 043,947; and Wallace 6,860,893; all incorporated here by reference.
[056] As previously described, some embodiments of the present invention may comprise polymers that are sufficiently soft and flexible that a substantially continuous length of the expandable element 1 will form in a secondary configuration similar to the configuration originally placed on the transport element 2 without pre-soften the device or expose it to blood, fluid or vapor.
[057] In some embodiments, the transport element 2 incorporates at least one space 7 that is dimensioned to allow the expandable element 1 to expand through the space (one embodiment of this configuration is shown in Figures 1-2). In other embodiments, the transport element 2 incorporates at least a space 7 that allows the expandable element 1 to be exposed to body fluids, but the expandable element 1 does not necessarily expand through the space (one embodiment of this configuration is shown in Figure 8). In other embodiments, no substantial space is incorporated into the transport element 2. Instead, the fluid is allowed to seep through the ends of the device or is injected through a lumen into the delivery system and the expandable element 1 expands and the forces its way through transport element 2.
[058] In an embodiment shown in Figure 1, the expandable element 1 comprises an expandable hydrogel based on poly (ethylene glycol) or acrylamide. The transport element 2 comprises a spiral. At least one space 7 is formed in the transport element 2. The expandable element 1 is disposed within the lumen 3 defined by the transport element 2 in a generally co-axial configuration. A tip 4 is formed at the distal end of the device 11, for example, by a laser, solder, adhesive, or casting the hydrogel material itself. The expandable element 1 can move continuously from the proximal end to the distal extremity, or it can move to a part of the device then terminate before reaching the distal or proximal end, or both.
[059] As an example, in one embodiment, the device is sized to treat a cerebral aneurysm. Those skilled in the art will appreciate that the dimensions used in this example could be scaled to deal with major or minor injuries. In this embodiment, the expandable element 1 is about 0.152 mm - 0.177 mm before expansion and about 0.50 mm after expansion. The expandable element is, for example, approximately 52% sodium acrylate, 48% poly (ethylene glycol) di-acrylamide with a molecular weight of about 8,000 grams / mol. About 0.4 g / g of sodium chloride (particle size of about 10 microns) is used as a porosigen and about 0.6 mg / ml of ammonium persulfate and 7 mg / ml of tetramethylethylene diamine is used as an initiator. The transport element 2 in this modality is a microspiral in the range of about 0.304 mm - 0.304 mm in diameter and has a thread between about 0.050 mm - 0.057 mm. In one embodiment, the transport element 2 comprises at least a space 7 between 1 to 3 long string dimensions. In another embodiment, the transport element 2 comprises at least one space 7 which is about 2 long rows. In one embodiment, the dimension of the gap 7 is between about 0.0381 mm and 0.1905 mm long. In another embodiment, the size of the gap 7 is between 0.057 mm and 0.1905 mm long.
[060] A coupler 13 is placed close to the proximal end to allow the implant 11 to be detachably coupled to a delivery system or pushed or injected through a catheter. Examples of distribution systems are found in Co-pending Order No. 11 / 212,830 for Fitz, US 6,425,893 for Guglielmi, US 4,994,069 for Richart, US 6,063,100 for Diaz, and US 5,690,666 for Berenstein; descriptions of which are incorporated herein by reference.
[061] In this embodiment, the implant 11 is constructed by formulating and mixing the hydrogel material as previously described in order to form the expandable element 1. The transport element 2 is wrapped around a helical or complex shape, and then heat hardened by known techniques the technique for forming a secondary diameter ranging from 0.5 mm to 30 mm and a varying length from 5 mm to 100 cm. After processing, washing and optional acid treatment, the expandable element 1 is threaded through the lumen 3 of the transport element 2. The distal end of the expandable element 1 is threaded through the lumen 3 of the transport element 2. The distal end of the element expandable 1 is then tied, for example, to form a knot, at the distal end of the transport element 2. Adhesive, such as UV-curable adhesive or epoxy, can be used to further improve the connection between the expandable element 1 and the transport element transport 2 and to form the distal tip 4. Alternatively, the tip can be formed, for example, by laser welding or spherical welding.
[062] In some embodiments, the space dimension 7 and the expanse ratio, handles and folds 12 can form as shown in Figure 7 when the expandable element 1 expands. It is desirable to prevent the formation of these loops or folds 12. This can be done by stretching the expandable element 1 either before placing it inside the transport element 2 or after the distal end of the expandable element 1 is attached to the transport element 2. For example, once the distal end of the expandable element 1 is attached to the transport element 2, the expandable element 1 is stretched such that its initial diameter of 0.254 mm is reduced to between about 0.152 mm - 0.177 mm before place it inside the transport element 2. After stretching, the expandable element 1 can be cut to match the length of the transport element 2 and then attached near the proximal end of the transport element 2 for example, by tying a knot, adhesive bonding or other techniques known in the art.
[063] Once implant 11 has been constructed, it is attached to a distribution system previously described by methods known in the art. The device can also be exposed, for example, to the electronic beam or gamma radiation to crosslink the expandable element 1 and control its expansion. This is described in U.S. Patent No. 6,537,569 which is assigned to the assignee of this application or incorporated here by reference.
[064] Previously, the secondary dimensions of previous devices (for example HES) are generally dimensioned to a dimension 1-2 mm smaller than the dimension (that is, volume) of the treatment site due to the relative stiffness of these devices. The increased flexibility and overall design of the implant 1 of the present invention allows the secondary shape of the implant 11 to be dimensioned to approximately the same size as the treatment site, or even slightly larger. This dimensioning also minimizes the risk of the implant moving or sliding out of the treatment site.
[065] Previous implant devices, such as the HES device, currently provide the user with about 5 minutes of repositioning time. However, the implant 11 of the present invention increases the length of the repositioning time. In some embodiments, the repositioning time during a procedure can be increased by approximately 30 minutes. In this regard, the user is provided with a longer repositioning time to obtain a better implant configuration.
[066] Figure 2 shows an implant 1 similar to that shown in Figure 1 after the expandable element 1 has expanded through space 7 to a larger dimension than the transport element 2.
[067] Figure 3 shows an implant 11 in which multiple expandable elements 1 move slightly parallel through the transport element 2. In one embodiment, this configuration is constructed by rotating a single expandable element 1 around the tip 4 of the implant 11 and tying both ends of the expandable element 1 to the proximal end of the transport element 2. In another embodiment, multiple strands of the expandable element 1 can be attached along the transport element 2. The construction of these modalities may also comprise stretching the expandable element 1 as previously described and / or form spaces in the transport element 2.
[068] Figure 4 shows an embodiment in which the implant 11 comprises a non-spiral transport element 2. In one embodiment, the transport element 2 is formed by cutting a plastic tube or sheet such as polyimide, nylon, polyester , polyglycolic acid, polylactic acid, PEEK, Teflon, carbon fiber or pyrolytic carbon, silicone, or other polymers known in the art with, for example, a cutting blade, laser, or water jet to form cracks, holes, or other fenestrations through which the expandable element 1 may be in contact with body fluids. The plastic in this embodiment can also comprise a radiopaque agent such as tungsten powder, iodine, or barium sulfate. In another embodiment, the transport element 2 is formed by cutting a tube or sheet of metal such as platinum, steel, tungsten, Nitinol, tantalum, titanium, chromium-cobalt alloy, or the like with, for example: acid etching , laser, water jet, or other techniques known in the art. In another embodiment, the transport element 2 is formed by braiding, forming meshes, or wrapping metal or plastic fibers in order to form fenestrations.
[069] Figure 5 shows an implant 11 comprising a transport element 2, an expandable element 1, and a stretch-resistant element 10. The stretch-resistant element 10 is used to prevent the transport element from stretching or unwinding during the distribution and repositioning. The stretch-resistant element 10 can be made of a variety of metal or plastic fibers such as steel, Nitinol, PET, PEEK, Nylon, Teflon, polyethylene, polyolefin, polyolefin elastomer, polypropylene, polylactic acid, polyglycolic acid and various other suture materials known in the art. The construction of the implant 11 can be fixing the ends of the stretch-resistant element 10 to the ends of the transport element 2 as described by U.S. 6,013,084 for Ken and U.S. 5,217,484 for Marks, both of which are incorporated by reference. Alternatively, the distal end of the stretch-resistant element 10 can be fixed close to the distal end of the transport element 2 and the proximal end to the stretch-resistant element 10 fixed in the distribution system as described in Co-pending Order N °. 11 / 212,830 for Fitz.
[070] Figure 6 is an alternative embodiment comprising a stretch-resistant element 10 wrapped around, tied to, or interwoven with the expandable element 1. This can occur over the length of the expandable element 1, or the winding or The bandage can be in only one area to facilitate the connection of the expandable element 1 to the transport element 2 using the stretch-resistant element 10 as a connecting element.
[071] Figure 7 shows a handle or fold 12 of the expandable element 1 projecting out of the transport element 2. In some embodiments, it may be desirable to avoid this condition, for example, by stretching the expandable element 1 as previously described. This would be done, for example, in modalities configured for delivery via a small microcatheter to prevent the implant 11 from being trapped in the microcatheter during delivery. In other embodiments, clearance can be added to the expandable element 1 so that the loop or fold will be preformed within the implant 11. This would be done in modalities where, for example, a large amount of volumetric filling is required because the straps or folds would tend to increase the total length of the expandable element 1.
[072] Figure 8 shows a modality in which the expandable element 1 is configured to expand to a dimension larger than its initial dimension, but smaller than the external dimension of the transport element 2. This can be done by adjusting the ratio of , for example, PEG di-acrylamide with sodium acrylate in modes where the expandable element 1 comprises a hydrogel. Alternatively, a relatively high radiation dose could be used to crosslink the expandable element 1, thereby limiting its expansion. Modalities as shown in Figure 8 are desirable when filling is necessary and it is desirable to have a substrate for tissue growth and proliferation that the expandable element 1 provides. In a modality used to treat cerebral aneurysms, this configuration could be used as a "filling" spiral. In one embodiment, the expandable element 1 comprises a hydrogel incorporating a porosigen as previously described to provide a cross-linked matrix to encourage cell growth and healing. Incorporating, for example, growth hormones or proteins into the expandable element 1 as previously described can further improve the ability of the implant 11 to obtain a biological response.
[073] Figures 9-11 illustrate another preferred embodiment of an implant 11 according to the present invention. This implant is generally similar to the previously described modalities, including an expandable element 1 that is arranged within a transport element 2. Additionally, a stretch-resistant element 10 is positioned along a longitudinal axis of the expandable element 1 and attached to the distal end of the transport element 2. The stretch-resistant element 10 is preferably located inside or partially circled by the expandable element 1. Preferably, the stretch-resistant element 10 is wrapped around a proximal part of the transport element 2 and fixed close to a heating coil 22 within a distal end of a distribution device 20, shown in Figure 11.
[074] As best seen in Figure 9, the proximal end of the transport element 2 can include a spiral region having a smaller diameter than the other spiral regions of element 2. This smaller diameter spiral region allows the stretch-resistant element 10 be wrapped around element 2 without extending out beyond the diameter of the other spiral regions of element 2. Additionally, a cover material 5 can also be positioned over the spiral region of smaller diameter without the handles of the element resisting. try to stretch 10 are exposed. This cover material 5 is preferably a laser, solder, adhesive or molten hydrogel material.
[075] As best seen in Figure 9, the spacing of the helical spirals of the transport element can vary along the length of the implant 11. For example, the spirals may be located close to each other or touching each other close to the distal ends and proximal while the central part of the implant 11 can have coils with larger spaces between them. In other words, the spaces between the coils may be larger over most of the implant 11 and smaller near the ends of the implant 11.
[076] In one embodiment, this implant 11 is created according to the following method. The expandable element 1 is created with hydrogel according to the techniques previously described in this report. In one embodiment, the expandable element VΘI 1 is formed in a polymerization tube between about 0.063 mm and 0.812 mm in internal diameter. After polymerization, the polymerization tube is cut into segments that are dried under vacuum. Once all the water has been removed from the hi-drogel, the dry hydrogel is pushed out of the polymerization tube using a mandrel. The hydrogel is then washed in water three times, swelling the hydrogel and removing sodium chloride and unreacted monomers.
[077] This expanded hydrogel is then spiked along its longitudinal axis (ie along an axis of its length) using a microspiral (or similar elongated tool). This skew creates a path along the approximate center of the hydrogel filament so that a stretch-resistant element 10 can be threaded through later. Then, the expected hydrogel is treated with acid by immersion in a hydrochloric acid solution, proponizing the carboxylic acid fractions of the sodium acrylate component of the polymer network, the spiked hydrogel is finally washed in alcohol to remove residual acid and dried under a vacuum.
[078] A platinum spiral with space is used for element 2, having an outside diameter ranging from about 0.304 mm to about 0.457 mm, varying string from about 0.0381 mm to about 0.0762 mm , and spaces 7 ranging from about 0.0381 mm to about 0.1905 mm. In another embodiment, the spaces 7 vary from about 0.057 mm to about 0.1905 mm. In one embodiment, this planer coil has an outer diameter of about 0.304 mm, a thread of about 0.050 mm, and a gap 7 of about 0.101 mm. In another embodiment, this platinum spiral has an outside diameter of about 0.317 mm, a thread of about 0.057 mm, and a gap 7 of about 0.114 mm. This platinum spiral with space is rolled over a mandrel and heat-hardened in a secondary helical shape. The platinum spiral is cut to a desired implant length and attached to a marking band or coupler 13 by means of soldering, welding or adhesive
[079] The spiral used to stick the hydrogel filament is removed, and a polyolefin stretch resistant thread of about 0.0558 mm for the stretch resistant element 10 is threaded through the filament along the path left by the spiral. The hydrogel filament, which now has an outside diameter between about 0.254 mm to about 0.457 mm, is stretched to an outside diameter between about 0.152 mm to about 0.304 mm and inserted into the platinum body spiral with space. While still under tension, the hydrogel filament is connected to the body spiral at both ends.
[080] The stretch-resistant thread is tied at the distal end of the platinum spiral and wound around the open spiral spaces at the proximal end (ie the end with the coupler 13). Both ends of implant 11 are covered with adhesive 4 and 5 to secure the stretch-resistant element 10 and encapsulate the ends of the expandable element 1. Finally, the implant 11 is attached to a detachment impeller using the resistant element to the stretch 10 that protrudes from the proximal end of the implant 11.
[081] During the use of implant 11 of this modality, implant 11 is advanced by means of a detachment impeller 20 through the microcatheter (not shown). When the distal end of the microcatheter has reached a desired target area, the impeller 20 is advanced, thereby pushing the implant 11 out of the microcatheter. When the user wishes to detach the implant 11, a heating coil 22 is activated to break the stretch-resistant element 10. Upon contact with blood, the pH-sensitive expandable element will expand to a final diameter between about 0.508 mm and 0.889 mm allowing the user about 5-10 minutes of working time.
[082] In another embodiment of the invention, implant 11 of Figure 9 includes a tensile-resistant element 10 composed of polyolefin and having an outside diameter of about 0.0558 mm. The expandable element 1 is composed of a hydrogel of about 48% PEG 8000 diacrylamide and 52% sodium acrylate. Element 2 is a platinum spiral with space having an outside diameter between about 0.304 mm and 0.508 mm and more preferably 0.304 mm. The element 2 has a thread between about 0.0381 mm and 0.127 mm, and more preferably about 0.050 mm. The space between the windings of the element 2 is preferably about 0.0762 mm.
[083] Figure 12 illustrates a preferred embodiment of an implant 11 similar to the previously described embodiment in which the spaces between windings of element 2 are preferably between about 0.050 mm and 0.508 mm. In addition, the implant contains one or more external elements 30 located at a proximal end of the implant 11, at a distal end of the implant, adjacent to the proximal or distal extremity of the implant, or in any combination of these locations. In the example in Figure 12, an external element 30 is positioned at the proximal and distal extremities of the implant 11.
[084] In one example, the outer element 30 is preferably composed of a platinum spiral having a length of about 0.254 mm and 3.048 mm, and more preferably between about 1.016 mm and 2.032 mm. The inner diameter of the outer element 30 is preferably between about 0.304 mm and 0.431 mm, and more preferably between about 0.304 mm and 0.317 mm. The wire of the outer element 30 preferably has a thread between about 0.0381 mm and 0.0762 mm and more preferably about 0.0381 mm.
[085] In another example, the outer element 30 is composed of a slotted tube having a length between about 0.254 mm and 3.048 mm, and more preferably between about 1.016 mm and 2.032 mm. The internal diameter of the slotted tube 30 is preferably between about 0.304 mm and 0.431 mm, and more preferably between about 0.304 mm and 0.317 mm. The thickness of the slotted tube is preferably between about 0.0254 mm and 0.0762 mm and more preferably 0.0381 mm.
[086] Figure 13 illustrates another preferred modality of implant 11 that is generally similar to the modality previously described. However, this implant 11 still comprises a closed coiled platinum spiral 32 disposed on the stretch-resistant element 10. Preferably, the stretch-resistant element 10 is composed of polyethylene and has an outside diameter of about 0.0228 mm. The closed coiled platinum spiral 32 preferably has an outside diameter of about 0.1524 mm and has a wire strand of about 0.0381 mm. The expandable element 1 is preferably composed of 48% PEG 8000 diacrylamide and 52% sodium acrylate. Element 2 is a platinum spiral with spaces having an outer diameter of about 0.012 mm and 0.0508 mm and more preferably between about 0.355 mm and 0.381 mm. The element 2 has a thread between about 0.00381 mm and 0.127 mm and more preferably about 0.050 mm. The space between the windings of the element 2 is preferably between about 0.050 mm and 0.508 mm and more preferably 0.101 mm.
[087] Preferably, the implant 11 of Figure 13 is created to prepare the expandable element 1 with hydrogel as previously described in this report. Before the acid treatment, the hydrated hydrogel is spiked with a platinum spiral 32. Preferably, the platinum spiral 32 is heat-hardened in a predetermined helical shape with a defined pitch and diameter before being spiked. A platinum-based and rigid mandrel is inserted into the platinum spiral 32 to provide transportation during additional treatments and implant construction 11.
[088] Following the acid treatment of the hydrogel, the mandrel is removed from within the platinum spiral 32 and replaced by the stretch-resistant element 10 (for example, a polyolefin monofilament). Optionally, both the mandrel and the platinum spiral 32 can also be removed and replaced by the stretch-resistant element 10. Element 2 (for example, a platinum spiral with spaces) is placed on the resulting subassembly and is sized appropriately to allow little or no free space within the inner diameter of element 2. Element 2 can be optionally rolled and heat-cured in a preliminary shape and preferably helicoidal of a defined pitch and diameter before placing on the hydrogel and the spiral platinum
[089] Once element 2 has been placed, it is attached to the hydrogel using adhesives at proximal and distal ends (preferably UV-cured adhesives). At this point, external elements 30 can optionally be located and connected at one or more ends of the implant 11.0 stretch-resistant element 10 is then attached at both ends of the implant 11 and the implant 11 is coupled to an electrical detachment mechanism such as described elsewhere in this report.
[090] In one embodiment of the invention a vessel-occlusive device comprises an expandable polymer element having an outer surface, a transport element that covers at least a part of the outer surface of the expandable polymer element, and in which no transport is disposed within the outer surface of the expandable element.
[091] In another embodiment, a vaso-occlusive device comprises a spiral having a lumen and a hydrogel polymer having an outer surface on which the hydrogel polymer is disposed within the lumen of the spiral and on which the hydrogel polymer is not. contains a spiral inside the outer surface of the hydrogel polymer.
[092] In another embodiment, a vaso-occlusive device comprises a transport element formed in a secondary configuration and an expandable element, in which the expandable element is made of a polymer formulated to have sufficient softness that the expandable element will substantially assume its shape. contact of the secondary configuration formed in the transport element without pretreatment.
[093] In another embodiment, a vessel-occlusive device comprises a transport element formed in a secondary configuration and a substantially continuous length of hydrogel, wherein the device substantially takes the form of the secondary configuration formed in the transport element without always an element expandable, in which the expandable element is made of a polymer formulated to have sufficient softness that the expandable element will substantially assume the contact of the secondary configuration formed in the transport element without pretreatment.
[094] In another embodiment, a vaso-occlusive device comprises a microspiral having an internal lumen and an expandable element disposed within the internal lumen. In this embodiment, the expandable element comprises a hydrogel selected from the group consisting of acrylamide, poly (ethylene glycol), Pluronic, and polypropylene oxide.
[095] In another embodiment, a vaso-occlusive device comprises a spiral and a hydrogel polymer disposed at least partially within the spiral in which the hydrogel has an initial length and in which the hydrogel polymer has been stretched to a second length which is longer than the initial length.
[096] In another embodiment, a vaso-occlusive device comprises an expandable element and a transport element defining an internal lumen, in which the expandable element is disposed within the internal lumen of the transport element and in which the expandable element has been stretched in a sufficient length to prevent a loop from the expandable element from protruding through the transport element.
[097] The invention described here includes a method of making a medical device. The method comprises providing a transport element having an inner lumen and an expandable element, inserting the expandable element into the inner lumen of the transport element, and drawing the expandable element.
[098] In another embodiment, a vessel-occlusive device comprises an expandable element encapsulated by a transport element, wherein said expandable element is comprised substantially whole and substantially uniform having an expandable property.
[099] In another embodiment, a vessel-occlusive device comprises a transport element and an expandable element in which the transport element has a secondary shape that is different from its primary shape and in which the expandable element is sufficiently flexible in a normal untreated state to conform to the secondary transport format.
[0100] In another embodiment, a vessel-occlusive device includes a transport and an expandable element in which the expandable element is fixed on the transport in such a way that the expandable element is in a stretched state during transport.
[0101] In another embodiment, a vessel-occlusive device includes a transport having several spaces along the transport and an expandable element positioned along an internal transport envelope and in which the expansion of the expandable element is controlled so that the expandable element expands within the spaces but not beyond the outer transport wrap.
[0102] In another embodiment, a vaso-occlusive device includes a transport element and an expandable element in which the expandable element is comprised of multiple strands extending along the transport.
[0103] In another embodiment, a vessel-occlusive device includes a transport and an expandable element in which the transport is a structure in a non-spiral cylindrical shape and in which said expandable element is disposed within said transport.
[0104] In another embodiment, a vessel-occlusive device includes a transport and an expandable element and a stretch-resistant element; said expandable element and said stretch-resistant element being disposed in an internal region of the conveyor and in which the stretch-resistant element is in tension in said conveyor.
[0105] The invention described here includes a method of treating an injury within a body. The method comprises providing a vaso-occlusive device comprising a transport element and an expandable element in which the transport element is formed in a secondary configuration that is approximately the same diameter as the lesion and inserting the vaso-occlusive device into the lesion .
[0106] In one embodiment, the transport element 2 is composed of a wire having a round cross-sectional shape. In other preferred modes, the transport element 2 of any of the modes shown in this report (or variations thereof) may have a non-round cross-sectional shape (for example, a cross-sectional shape with a diameter not uniform or varied at different angles or locations across the cross section). For example, Figure 14 illustrates a wire 50 with a generally oval cross-sectional shape, Figure 15 illustrates a wire 52 with a "D" cross-sectional shape or half a circle, Figure 16 illustrates a wire 56 with a "double D" shape, a half-circle with a central depression, or a channeled half-circle shape, and Figure 17 illustrates a U-shaped or arched cross-section shape.
[0107] These non-round cross-section wire shapes can provide performance characteristics that may be desirable in some uses. Such a feature can be seen in figure 18, which compares a transport element 2 with a wire of round cross section 51 with that of a wire 50 with an oval cross section. The expandable element 1 can typically extend a limited distance beyond the internal diameter of the implant 11 (shown as the distance 55 in Figure 18). In some configurations of device 11 using hydrogel, the expandable element 1 can expand between 0.101 mm - 0.152 mm beyond the internal diameter of the implant before cracking or breaking.
[0108] By decreasing the thickness of the wire 50, the expandable element 1 can expand a greater distance beyond the outer diameter 52 of the implant 11. Therefore, the implant 11, as a whole, can swell or expand to a diameter greater than an implant having a round cross-section wire 51 but width, spiral spacing and other similar performance characteristics.
[0109] In a more specific example, wire 51 has a diameter of 0.304 mm and forms an implant with an internal diameter of 0.203 mm and an external diameter of 0.304 mm. Wire 50 has a cross section of 0.0254 mm x 0.101 mm with an internal diameter of 0.254 mm. The expansion limit of the internal diameter of the implant is around the same for each example (for example, between 0.101 mm - 0.152 mm), which therefore allows about 0.050 mm of additional expansion diameter in the implant using wire 50.
[0110] It should be noted that reducing the diameter of wire 51 to a thickness similar to that of wire 50 can achieve similar expansion diameters of expandable element 1, but can sacrifice other important performance characteristics. For example, decreasing the wire mass also decreases the “pushing ability” of the implant 11. In other words, reducing the wire mass can decrease the strength of the spiraled implant column and therefore increase the implant's probability bend, be damaged or similar complications. In another example, reducing the wire mass can also reduce the radiopacity of the implant and therefore can be difficult to visualize during a procedure.
[0111] In contrast, non-round wires 50, 52, 56 and 58 can provide similar column strength and radiopacity when compared to a gun with similar mass 51 while increasing the internal diameter of the implant 11. Additionally, some non-round cross-section wire may provide greater column strength and radiopacity when compared to round cross-section wires with similar masses 51.
[0112] Additionally, non-round wires 50, 52, 56 and 58 can provide frictional drag which is similar to those of round wire 51, especially if the non-round wire has a non-flat surface oriented out of the implant 11. For example, wires 50, 52, 56 and 58 all include rounded or non-flat surfaces that, when oriented out of the implant 11, can provide a similar amount of surface area that can contact an internal lumen of a catheter distribution when compared to a wire with similar mass 51.
[0113] The distal end of an implant tends to contact the patient's blood for a longer period of time during a procedure. Often, this distal exposure results from blood partially entering the catheter during advancement to a target area and the distal end being pushed from the catheter first (and therefore being completely exposed for the longest time). Such expansion of the expandable material 1 can be triggered by exposure to blood for a period of time, the expandable material near the distal end of an implant may otherwise expand completely first and thereby limit the user's ability to retract and reposition the device within a patient.
[0114] The implant 60 in Figure 19 can reduce the premature expansion of its distal end (that is, increase its exposure time to fully expand its expandable material). Specifically, the implant 60 includes a distal region 62 in which its loops are "closed closed" or placed immediately in contact with adjacent loops so as to be without space (when opposed to the "curled open" configuration or with spaces in the proximal region 64) . This configuration can reduce the amount of expandable material 1 near the distal ex-tremity that is contacted by the blood prior to the complete deployment of a catheter implant 60.
[0115] The initial blood exposure in the distal parts of the expandable element 1 is further reduced by ending the distal end of the expandable element near region 62. In other words, the expandable element 1 is located only within the open, proximal coiled region. 64. In this regard, blood exposure in the distal part of the expandable element 1 can be reduced, allowing a user more time to position or reposition the implant 60 on the patient before such actions are limited by the expansion of the expandable element 1.
[0116] In one example, the proximal region 64 has a space dimension between its spirals between about 0.0254 mm and about 0.254 mm. In a more specific example, the space dimension of the proximal region 64 is about 0.0762 mm.
[0117] In another example, the transport element 2 is a non-circular wire having a thread width between about 0.0254 mm and about 0.254 mm and a thread thickness between about 0.0127 mm at about 0.2032 mm. In a more specific example, the transport element 2 has a row width of about 0.101 mm and a row thickness of about 0.0457 mm.
[0118] In another example, implant 60 has an outside diameter between about 0.2032 mm and about 0.6604 mm. While the exemplary dimensions, previously described, are applicable to implant 60, it must be understood that these dimensions are also possible for any of the other modalities discussed in this report, especially those shown in Figures 20 and 21.
[0119] Figure 20 illustrates a part of an implant 70 according to the present invention that is in general similar to the devices previously described in this embodiment. However, the implant 70 includes several connected or fused loop regions 72 that are located along the length of the implant 70. Therefore, the implant 70 alternates between the regions of the open looped loops or with spaces and regions of directly connected loop 72. These regions 72 can effectively increase the total spring constant of the implant 70 (when compared to a similar implant without the regions 72), thereby improving the “pushability” of the implant for ease of being pushed out of a catheter without bending or similar undesirable movement.
[0120] As seen in Figure 20, each region can include two connected loops. Alternatively, any number of loops can be connected together, such as between 2 and 6 loops. The handles can be connected to each other by means of a solder joint 74, glue, solder or similar connection techniques. Regions 72 can be located at any regular intervals or distances from each other, such as the three loop range in Figure 20. Alternatively, implant 70 may have different spacing areas between regions 72 (for example, discrete regions different distances or progressively increasing / decreasing along the length of the implant 70 to its distal end). For example, the distal and proximal ends may have regions 72 that are closer than a mid-region. In another example, the length between regions 72 may increase from the proximal to the distal end of the implant 70.
[0121] Figure 21 illustrates a similar variation of implant 70. However, implant 80 includes regions of fixed distance 82 in which the elongated fasteners 84 maintain adjacent handles at a predetermined distance from each other. These fasteners 84 can be welded, adhered or connected in adjacent loops in order to prevent relative movement between the loops of region 82. The fixed distance regions 82 are preferably followed and followed by the non-fixed regions (ie , distally and proximally). While only two connected loops are shown as part of region 82, any number of loops can be connected (for example, 3, 4, 5, 6, 7, 8, 9, and 10). Preferably, the loops of region 82 have a spacing from each other similar to (i.e., approximately the same as) the other loops of implant 80, such that all loops of the implant are relatively uniformly spaced. Alternatively, the loops of region 82 may be spaced differently than loops that do not touch fastener 82 (i.e., larger or smaller).
[0122] As with implant 70, regions 82 can be spaced in a number of different configurations along the length of device 80. For example, regions 82 can be located along only part of the length of the device, in intervals increasing / decreasing regularly or in discrete segments of different spacing. Again, these fasteners 84 can effectively increase the total spring constant of the implant 80 (when compared to a similar device without the 82 regions), thereby improving the “pushability” of the device or ease of being pushed into out of a catheter without bending or similar unwanted movement.
[0123] Figures 22-24 illustrate an alternative embodiment of an implant 90 of the invention. The helical transport element 2 has an unstressed initial diameter (for example, a spiral that is heat hardened in an initial helical shape) as shown in Figure 22. The expandable element 1 is placed inside the transport element 2 and stuck in transport 2 by means of UV adhesive, or other methods previously described. The expandable element is placed under tension, such as by stretching, in order to reduce the radial profile of the element which correspondingly reduces the radial profile of the fixed transport element, which is attached to the expandable element, as shown in Figure 23. When the implant is placed in a physiologically appropriate medium (ie, blood or phosphate buffer solution), the expandable example swells causing the restricted transport diameter to swell and return to its unrestricted state, as shown in Figure 24.
[0124] Different sections of the transport could be restricted at different voltage levels in order to form variable restricted diameters. For example, the distal or proximal end of the transport could be restricted to a level of tension greater than the other end, or the level of tension could vary axially throughout the transport element. This would allow for a variable restricted and variable expanded / unrestricted implant shape that can be useful to fill space in more challenging geometric shapes.
[0125] In one example, in order to help maximize the amount of swelling of the expandable element, said element is preferably not stretched to a significant degree before being attached to the transport element. Certain previous modalities have described the stretching of the expandable element prior to adhesion to the transport element, for example, in order to prevent folds from forming during expansion. However, stretching to a significant degree could limit the amount of expansion of the element, since it is exposed to the physiologically appropriate medium.
[0126] This modality can function effectively as a framing spiral, where the implant placement is easier due to the smaller restricted dimension of the implant, and where the larger unrestricted dimension, swollen of the implant with time allows a more secure around the periphery of the aneurysm, or vessel deformation. This modality can also function effectively as a filling or finishing spiral, where the restricted implant diameter allows easier implant placement (especially in tight spaces) and the unrestricted, bloated diameter would maximize the filling of the implant. space.
[0127] Although the preferred embodiments of the invention have been described in this report and the accompanying drawings, it will be appreciated that a number of variations and modifications may suggest to those skilled in the relevant technique. Thus, the scope of the present invention is not limited to the specific modalities and examples described here, but should be considered to encompass alternative and equivalent modalities.
[0128] Unless otherwise stated, all figures that express quantities of ingredients, properties such as molecular weight, reaction conditions, and so on used in the report and claims must be understood to be modified in all cases. cases by the term “about”. Consequently, unless otherwise indicated, the numerical parameters described in this report and appended claims are approximations that may vary depending on the desired properties to be obtained by the present invention. At a minimum, and not as an attempt to limit the application of the doctrine of equivalents within the scope of the claims, each numerical parameter must at least be constructed in light of the number of significant digits reported and applying common rounding techniques. Although the numerical variations and parameters representing the broad scope of the invention are approximations, the numerical values represented in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in its respective test measurements.
[0129] The terms "one", "one", "o", "a" and similar referents used in the context of describing the invention (especially in the context of the following claims) must be constructed to cover the singular and the plural, unless otherwise indicated here or clearly contradicted by context. The enumeration of ranges of values here is merely intended to serve as an abbreviated method of referring individually to each separate value within the range. Unless otherwise indicated here, each individual value is incorporated into the report as if it were individually indicated here. All methods described here can be performed in any suitable order unless otherwise indicated here or otherwise contradicted by context. The use of any and all examples, or exemplary language (for example, "such as") provided here is intended merely to better illuminate the invention and does not represent a limitation on the scope of the invention otherwise claimed. No language in the report should be constructed as indicating any unclaimed elements essential to the practice of the invention.
[0130] Groupings of alternative elements or modalities of the invention, described here, should not be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other members found here. It is expected that one or more elements of a group can be included in, or deleted from, a group for reasons of convenience and / or patentability. When any inclusion or deletion occurs, the report is considered to contain the group as modified thus satisfying the written description of all Markush groups used in the attached claims.
[0131] Certain embodiments of this invention are described here, including the best known way for the inventors to carry out the invention. Of course, variations in these described modalities will become evident to those skilled in the technique of reading the preceding description. The inventor expects specialists to employ such variations where appropriate, and the inventors intend for the invention to be practiced in a manner that is specifically described herein. Consequently, this invention includes all modifications and subject equivalents recited in the appended claims as permitted by applicable law. Furthermore, any combination of the elements described above in all possible variations thereof is covered by the invention unless otherwise indicated here or otherwise clearly contradicted by context.
[0132] In addition, numerous references have been made to patents and printed publications throughout this report. Each of the aforementioned references and printed publications are individually incorporated herein by reference in their entirety.
[0133] In conclusion, it should be understood that the modalities of the invention described here are illustrative of the principles of the present invention. Other modifications that can be employed are within the scope of the invention. Thus, by way of example, but not limitation, alternative configurations of the present invention can be used in accordance with the teachings here. Consequently, the present invention is not limited to that precisely shown and described.

权利要求:
Claims (9)
[0001]
1. Vaso-occlusive device for body cavities, comprising: a helical transport element (2) formed of wire (50, 52, 56, 58) having a non-circular cross-sectional shape and being oriented so that a surface does not the plane of said wire (50, 52, 56, 58) is oriented outwardly from said vessel-occlusive device; CHARACTERIZED by the fact that the vaso-occlusive device comprises an expandable element (1) disposed within said helical transport element (2); wherein the helical transport element (2) incorporates at least one space (7) which is sized to allow the expandable element (1) to expand through said space (7) and the expandable member is configured to expand through the said space (7).
[0002]
2. Vaso-occlusive device, according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape has a diameter that varies in length in different locations.
[0003]
3. Vaso-occlusive device, according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is oval.
[0004]
4. Vaso-occlusive device according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is a half-circle shape.
[0005]
5. Vaso-occlusive device according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is a half-circle shape having a central depression.
[0006]
6. Vaso-occlusive device, according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is a double D shape.
[0007]
7. Vaso-occlusive device according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is a half-circle shape with a medium channel.
[0008]
8. Vaso-occlusive device, according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is an arc shape.
[0009]
9. Vaso-occlusive device, according to claim 1, CHARACTERIZED by the fact that said non-circular cross-sectional shape is a U shape.

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AU2012340527B2|2017-07-13|

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法律状态:
2018-12-04| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-10-08| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-07-28| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2020-10-20| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 21/11/2012, OBSERVADAS AS CONDICOES LEGAIS. |

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