WO1993000128A1 - Renewable neural implant device and method - Google Patents
Renewable neural implant device and method Download PDFInfo
- Publication number
- WO1993000128A1 WO1993000128A1 PCT/US1992/005389 US9205389W WO9300128A1 WO 1993000128 A1 WO1993000128 A1 WO 1993000128A1 US 9205389 W US9205389 W US 9205389W WO 9300128 A1 WO9300128 A1 WO 9300128A1
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- WIPO (PCT)
- Prior art keywords
- cell chamber
- cells
- chamber
- cell
- mandrel
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/022—Artificial gland structures using bioreactors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/06—Head
- A61M2210/0687—Skull, cranium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/06—Head
- A61M2210/0693—Brain, cerebrum
Definitions
- the technical field of this invention is the treatment of neurological disorders and, in particular, the treatment of diseases and disorders which may be remedied by treatment with secretory substances, such as neurotransmitters, neuromodulators, hormones, trophic factors, or growth factors. All these substances are characterized by the fact they are secreted by "source” cells and produce a specific change in the source cell itself or in a "target” cell (i.e., they are biologically active) .
- secretory substances such as neurotransmitters, neuromodulators, hormones, trophic factors, or growth factors. All these substances are characterized by the fact they are secreted by "source” cells and produce a specific change in the source cell itself or in a "target” cell (i.e., they are biologically active) .
- paralysis agitans more commonly known as Parkinson's disease
- Parkinson's disease is characterized by a lack of the neurotransmitter, dopamine, within the striatum of the brain, secondary to the destruction of the dopamine secreting cells of the substantia nigra.
- Affected subjects demonstrate a stooped posture, stiffness and slowness of movement, and rhythmic tremor of limbs, with dementia being often encountered in very advanced stages of the disease.
- Brain derived growth factor also may have potential value in the treatment of Parkinson's disease since it has been demonstrated to maintain the viability of striatal neurons in. vitro.
- microcapsules i.e., tiny spheres which encapsulate a microscopic droplet of a cell solution
- microencapsulation approach there are a number of shortcomings to the microencapsulation approach.
- the microcapsules can be extremely difficult to handle, including being difficult to retrieve after implantation.
- the types of encapsulating materials which can be used are constrained by the formation process to polymers which can dissolve in biocompatible solvents.
- due to the limited diffusional surface area per unit volume of larger size spheres only a limited amount of tissue can be loaded into a single microcapsule.
- macroencapsulation typically involves loading cells into hollow fibers and then sealing the extremities.
- macrocapsules offer the advantage of easy retrievability, an important feature in therapeutic implants, especially neural implants.
- the construction of macrocapsules in the past has often been tedious and labor intensive.
- conventional methods of macroencapsulation have provided inconsistent results.
- Refillable immunoisolatory therapy devices are disclosed for the local and controlled delivery of a biologically active factor to the brain of a patient.
- the devices generally include a cell chamber adapted for infusion with biologically active factors, or cells that secrete such factors.
- the cell- chamber includes a semipermeable surface across which the active factors move for delivery to the brain.
- the devices also include means for introducing such cells or factors to the cell chambers, and a means for renewing the cells or factors.
- the cell chamber is constructed as a U-shaped tube having ports for filling, flushing, and/or refilling the cell suspension.
- the ports may be the same or different ports, and can be sealed to prevent introduction of extraneous material into the cell chamber.
- the U-shaped tube may include a support structure, such as a mandrel, for providing structural support to the cell chamber during surgical insertion in the brain.
- the mandrel may be a solid centerboard mandrel adapted to fit with and support the walls of the U-shaped tube.
- the mandrel may be a selectively collapsible mandrel that can be removed once the cell chamber is positioned in the brain.
- the collapsible mandrel may include one or more flanges or tabs which function to secure the mandrel within the U-shape of the cell chamber during insertion.
- a solid centerboard mandrel is initially positioned within the U-shape of the cell chamber, and a substantially rigid shield element is positioned over the mandrel and cell chamber. The entire assembly is then positioned within the brain, and both the mandrel and the shield may be removed.
- the shield may include tab elements which interfit with an aperture in the solid mandrel to enable these two elements to be removed from the brain substantially simultaneously, leaving the cell chamber in position.
- the device may be a coaxial double lumen tube assembly.
- the cell chamber is coextruded with a polymer casting solution to form an encapsulated cell chamber.
- the cell chamber may then be a concentric lumen chamber having ports connected to an inner and an outer lumen for filling, flushing, and/or refilling.
- the biologically active factor-secreting cell may include any cell which is known, or has been engineered to produce neuropeptides, trophic factors, or neurotransmitters, or agonists, precursors, active analogs, or active fragments thereof.
- chromaffin cells of the adrenal medulla, embryonic ventral mesencephalic tissue, and various neuroblastic cell lines such as PC12 function to supply dopamine, and therefore, are preferred for incorporation into the device.
- the cell is allospecific (i.e., cells from another of the same species as the subject in which it is to be implanted) or xenospecific (i.e., cells from another of a different species) .
- the encapsulated cells, or cells contained in the cell chamber of the invention include neurosecretory cells that secrete biologically active factors such as gamma aminobutyric acid, serotonin, acetylcholine, norepinephrine, endorphins, enkephalins, dopamine, and precursors, agonists, active analogs, and active fragments thereof.
- the cells may also secrete a dopamine precursor, such as L-dopa, or a dopamine agonist, such as bromocriptine.
- Other factors, and cells secreting such factors may be used in practicing the present invention.
- biologically active factprs used herein includes neurotransmitters such as gamma aminobutyric acid, serotonin, acetylcholine, epinephrine, norepinephrine, gluatmic acid.
- the term also includes fibroblast growth factors and dopamine.
- the term further includes precursors, agonists, active analogs, and active fragments of these neurotransmitters (e.g. dopamine precursor L-dopa and dopamine agonist bromocriptine) .
- Cells that secrete peptide factors such as peptide neurotransmitters, growth factors, trophic factors and/or hormones may also be useful.
- insulin include: insulin, Factor VIII, trophic factors such as erythropoeitin and growth hormones, biological response modifiers such as lymphokines and cytokines, enzymes, and antibodies from antibody-secreting cells, neuropeptides such as enkephalins, dynorphins.
- Substance P, and endorphins as well as factors such as nerve growth factor (NGF) , brain-derived neutrophic factor (BDNF), neurotrophin-3 (NT-3), an array of fibroblast growth factors, and an array neurotrophic factor.
- NGF nerve growth factor
- BDNF brain-derived neutrophic factor
- NT-3 neurotrophin-3
- an array neurotrophic factor an array neurotrophic factor.
- the cell chamber may also include a hydrophobic matrix, such as an ethylene vinyl acetate copolymer, or a hydrophilic matrix such as a hydrcgel.
- a hydrophobic matrix such as an ethylene vinyl acetate copolymer
- a hydrophilic matrix such as a hydrcgel.
- the cell chambers may be ppst-prpducticn coated or treated with an impermeable outer coating, such as a polyurethane, ethylene vinyl acetate, silicon, or alginate covering part of the cell chamber.
- FIG. 1 is a graphic representation pf a single plate mpunt embodying multiples of the system of the present invention
- FIGS. 2A - 2D are side elevation views of cell encapsulation vehicles used in practicing the present invention.
- FIG. 3 is a perspective view of a vehicle embodying the centerboard mandrel embodiment of the invention.
- FIG. 4A is a cross-sectional side view of a vehicle embodying the collapsible mandrel of the invention
- FIGS. 4B and 4C are top and bottom cross-sectional views of the vehicle of FIG. 4A, respectively;
- FIG. 5 is an orthogonal side view in cross-section of the vehicle of FIG. 4A;
- FIG. 6 is a perspective view of a vehicle embodying the present invention.
- FIG. 7 is a series of perspective views of a vehicle embodying the present invention, which also integrates protective shields about the tip of the implant during surgical placement, which shields are retractable prior to centerboard removal;
- FIG. 8A is a cross-sectional side view of another vehicle embodying the present invention; and
- FIG. 8B is a top cross-sectional view of the vehicle of FIG. 8A.
- FIG. 9 is an orthogonal side view in cross-section of the vehicle of FIG 8A.
- FIGS. 10A - 10D are a series of longitudinal-section views of a camming shield embodiment of the invention, the series illustrating operation of the shield;
- FIG. 11A is a cross-sectional side view of a double lumen vehicle used in practicing the present invention.
- FIGS 11B and 11C are top and bottom cross-sectional views of the vehicle of FIG. 11A, respectively;
- FIG. 12 is a longitudinal-section view of a double lumen embodiment of a vehicle of the present invention, also showing a means for filling/flushing using an applied nozzle;
- FIG. 13 is a perspective view of another embodiment of a vehicle embodying the invention.
- FIG. 14 is a longitudinal-section view of the vehicle of FIG. 13.
- Refillable immunoisolatory neurological therapy devices for the constitutive and controlled delivery of biologically active factors to a target treatment site of a patient suffering from a neurological deficiency or dysfunction.
- the inventive device includes a cell chamber for infusion of cells which secrete biologically active factors.
- the chamber has at least one semipermeable surface across which biologically active factors secreted by the cells can be delivered to the surrounding tissue, such as the brain.
- the device also includes means for introducing cells to the chamber, and means for renewing the cells contained in the chamber.
- FIG. 1 illustrates several devices 10 attached to a plate mount 12 positioned above the insertion sites 14 of a patient's skull just prior to delivery to a treatment site.
- the devices 10 may be generally U-shaped.
- the devices may have different configurations while performing substantially the same function.
- FIG. 2A illustrates a device 10a having a cell chamber 20 that is U-shaped to increase the surface area and having a port 22 for refilling the cell chamber 20.
- FIG. 2B illustrates a U-shaped cell chamber 20 similar to that of FIG. 2A, including a manifold 24 to protect the cell chamber 20 during insertion.
- FIG. 2C illustrates a double lumen device 10c that includes an outer lumen cell chamber 20 for carrying the biologically active factors, and a second inner lumen for flushing the cell chamber cells.
- FIG. 2d illustrates a single tube lOd having an inner cell chamber 20 containing the neuroactive factors, and an outer protective coating 26 which serves to encase at least part of the cell chamber.
- FIG. 2e illustrates a cell chamber encapsulated in a semi-permeable or permselective membrane 28 with an attached tether 30.
- the membrane 28 permits diffusion of the neuroactive factors from the cell chamber 20 to the treatment site once the device lOe is positioned.
- a standard U-shaped cell chamber 20, of the type shown in FIG. 2A, absent the center supportive strut 25, may be fitted with a centerboard-type mandrel 24 having side slots 32 adapted to receive the cell chamber 20. Since each device 10 of the invention is designed to be mounted to the patient's skull, a cap 34 is attached to the top end portions of the U-shaped cell chamber 20 secure the shape of the chamber 20. The cap 34 includes the port 22 used for refilling the cell chamber solution.
- the mandrel 24 of FIG. 3 is designed to support the U-shaped cell chamber 20 during implantation through the insertion site 12 and to the treatment site in the patient.
- the mandrel 24 is designed to slidably fit through an insertion port 36 in the cap 34 prior to delivery of the device 10b to the brain.
- the mandrel 24 includes a solid center plate 18 which is substantially rigid to prpvide suppprt tp the circumferential cell chamber 20.
- the mandrel 24 further includes a top portion 16 which may act as a stop point during insertion through the insertion port 36.
- the human brain can move within the cranium, there is strain caused between an implant fixed to the skull and the movable brain tissue.
- the mandrel 24 is generally removed after placement of the cell chamber 20 to facilitate flexibility of the chamber 20 once it is positioned.
- the chamber 20 is generally manufactured from a flexible material to allow the structure to compensate for such movement of the cranium, to which the chamber 20 is attached, relative to the brain, into which the chamber 20 is inserted.
- Polymeric membranes forming the cell chambers may include polyacrylates (including acrylic copolymers), polyvinylidenes, polyvinyl chloride copolymers, polyurethanes, polystyrenes, polyamides, cellulose acetates, cellulose nitrates, polysulfones, polyphosphazeres, polyethylene oxides, polyacrylonitriles, as well as derivatives, copolymers, and mixtures thereof.
- the sclvents used in conjunction with the above-identified polymers in forming the cell chambers 20 will depend upon the particular polymer chosen for the membrane material.
- Suitable solvents include a wide variety of organic solvents, such as alcohols and ketones generally, as well as dimethylsulfoxide (DMSO) , dimethylacetamide (DMA) , and dimethylformimide (DMF) . In general, water-miscible organic solvents are preferred.
- organic solvents such as alcohols and ketones generally, as well as dimethylsulfoxide (DMSO) , dimethylacetamide (DMA) , and dimethylformimide (DMF) .
- DMSO dimethylsulfoxide
- DMA dimethylacetamide
- DMF dimethylformimide
- the polymeric solution, or "dope” can also include various additives, including surfactants to enhance the formation of porous channels, as well as antioxidants to sequester oxides that are formed during the coagulation process.
- surfactants include Triton-X 100 available from Sigma Chemical Corp., and Pluronics P65, P32, and P18.
- antioxidants to sequester oxides that are formed during the coagulation process.
- Exemplary surfactants include Triton-X 100 available from Sigma Chemical Corp., and Pluronics P65, P32, and P18.
- Exemplary anti-oxidants include vitamin C (ascorbic acid) and vitamin E.
- anti-inflammatory agents, angiogenic factors, and cell growth factors can also be incorporated into the polymeric membrane to reduce immune response or to stimulate cell culture, respectively.
- Exemplary anti-inflammatory agents include corticoids such as cortisone and ACTH, dexamethasone, cortisol, interleukin-1 and its receptors and agonists, an antibodies to TGF, to interleukin-1, and to interferon-gamma.
- Exemplary angiogenic factors include fibroblast growth factor and nerve growth factor.
- these materials can be added to the devices after manufacture or formation by a post-coating or spraying process.
- the devices can be immersed in a solution containing an anti-inflammatory agent, an angiogenic factor, or a growth factor. Post-coating procedures can also be used to provide a protective barrier against immunogens and the like.
- the cell chambers can be coated (e.g., by immersion, spraying or applying a flowing fluid during extrusion, if applicable) with a surface protecting material, such as polyehtylene oxide or polypropylene oxide to inhibit protein interactions with the exposed cell chambers.
- a surface protecting material such as polyehtylene oxide or polypropylene oxide to inhibit protein interactions with the exposed cell chambers.
- Other protective coatings include silicon, and hydrogels such as alginates.
- Multi-compartment cell vehicles are particularly useful for the constitutive delivery of neurotransmitters, such as dopamine, which is secreted by cells of the adrenal medulla, embryonic ventral mesencephalic tissue and neuroblastic cell lines.
- neurotransmitters such as dopamine, which is secreted by cells of the adrenal medulla, embryonic ventral mesencephalic tissue and neuroblastic cell lines.
- PC12 cells an immortalized cell line derived from a rat pheocromocytoma
- Other neurotransmitters include gamma aminobutyric acid (GABA), serotonin, acetylcholine, noradrenaline, peptide neutrotransmitters, and other compounds necessary for normal nerve functions.
- GABA gamma aminobutyric acid
- serotonin serotonin
- acetylcholine acetylcholine
- noradrenaline noradrenaline
- peptide neutrotransmitters and other compounds necessary for
- a number of cell lines are known or can be isolated which secrete these neurotransmitters.
- Cells can also be employed which synthesize and secrete agonists, analogs, derivatives or fragments of neurotransmitters which are active, including, for example, cells which secrete bromocriptine, a dopamine agonist, and cells which secrete L-dopa, a dopamine precursor.
- the encapsulated cells can be chosen for their secretion of hormones, cytokines, growth factors, trophic factors, angiogenesis factors, antibodies, blood coagulation factors, lymphokines, enzymes, and other therapeutic agents.
- Other biologically active factors may include neurotransmitters, peptides, and trophic factors.
- Exemplary biologically active peptides include enkephalins, endorphins, dynorphin, and Substance P.
- Exemplary factors include nerve growth factor (NGF) , platelet-derived growth factor (PDGF), epidermal growth factor (EGF) , brain-derived neurotrophic factor (BDNF), neurotro ⁇ hin-3 (NT-3), an array of fibroblast growth factors, and ciliary neurotrophic factor.
- the aqueous cell suspensions in the cell chambers 20 can further include various additives to protect the cells during the extrusion process or to stimulate their growth subsequently.
- additives may include, for example, a nutrient medium or growth factors which are incorporated into the aqueous suspension, as well as an anchorage substrate material to enhance cell attachment.
- the anchorage substrate material can be a proteinaceous material, such as collagen, laminin, or polyamino acids.
- the cell suspension or the polymeric solution (or both) can include a foaming agent or a blowing agent which can distort the inner surface of the polymeric coating to increase the anchorage surface area of the tubular interior.
- the inventive device 10 includes a plug 38 which is placed over the cap 34, or fits integral with the cap 34 to cover the filling ports 22 and insertion port 36.
- the plug 38 may be manufactured from silicone, or any material capable of being formed into the desired configuration. The principle function of such as plug 38 is to keep contaminants " out of the ports 22, 36 when the device 10 is in position within a patient.
- FIGS. 4A-4C and 5 An alternative embodiment of a manifold 24 used in supporting the cell chamber 20 in a device of the present invention is shown in FIGS. 4A-4C and 5 which present side and end views of device 10b, respectively.
- the mandrel 24 is collapsible to accommodate for insertion of the mandrel 24 in the U-shaped portion of the device 10b'.
- the cap 34 is adapted to fit with the plate mount 12.
- the mandrel 24 includes a top portion 16 to stop the mandrel while it is inserted through the insertion port 36.
- the illustrated mandrel 24 of FIGS. 4A-4C further includes a collapsible center portion 42 having side portions 44 which move toward each other during movement through the port 36, and which expand away from each other once they are within the U-shaped portion of the cell chamber 20.
- the mandrel 24 may further include flanges 46 that extend from the side portions 44.
- the flanges 46 are designed to prevent the mandrel 24 from lifting out from between the U-shaped cell chamber 20 during insertion of the device 10b' into the patient's brain. This is achieved by positioning the flanges 46 near the base of the cap 34 so that once the flanges 46 pass entirely through the insertion port 36 and below the cap 34, they form a wedge beneath the cap 34.
- the entire mandrel 24 may be removed by lifting the cap 34 along with the mandrel 24 once the cell chamber 20 is in the desired position.
- the sleeve 50 may be inserted into the cap 34 of the device 10b' .
- the sleeve 50 may include one or more fill tubes 52, each fill tube 52 positioned to align with the fill ports 22 of the device 10b' .
- the sleeve may further include a flange 54 adapted to interfit with the insertion port 36, which is also used to insert the mandrel 24.
- the sleeve 50 may be manufactured from any suitable, maleable material which may be formed into the desired shape. Since the sleeve 50 does not come in direct contact with the patient, there is no specific requirement that it be biocompatible although the sleeve 50 would typically be sterilized before use. Further, since it is a conduit for the tubes 52 carrying biological material, there is no special requirement for it to be compatible with the transported biological material, e.g., biologically active factors.
- the mandrel 24 includes two separate portions: a center mandrel 60, similar to the centerboard mandrel of FIG. 3; and, a shield 62.
- the center mandrel 60 is held in place within the shield 62 by tabs 66 on one or both legs 64.
- the tabs 66 snap into the tab aperture 68 on the center mandrel.
- the center mandrel 60 further includes a ridge 58 on its bottom-most portion adapted to receive the bottom radius of the cell chamber 20.
- the center mandrel 60 slides through the insertion port 36 until the bottom ridge 58 is fitted within and receives the bottom radius of the cell chamber 20.
- Flanges 70 on the center mandrel snap under the cap 34.
- the shield 62 is inserted within the insertion port 36, its legs 64 sliding along the walls 61 of the center mandrel.
- the legs 64 of the shield cover the walls 61.
- the legs 64 are generally slightly longer than the length of the center mandrel walls 61 to enable the shield 62 to extend around the entire cell chamber 20 and mandrel 60.
- the tip portion 72 of each leg 64 may be adapted to form a closure upon positioning of the shield 62, the legs 64 being slightly outwardly flexible to
- SUBSTITUTE permit the legs to form a gap when being moved into position over the cell chamber 20, yet close once in position.
- FIGS. 10A - 10D removal of the center mandrel 60, along with the shield 62 is illustrated.
- the entire mandrel assembly may be removed. Pulling up on the cap 34 causes the shield 62 to cam open against the center mandrel by its tabs 66.
- the legs 64 slightly outwardly flex open to enable them to open around the bottom of the center mandrel wall 70 (shown in FIG. 10B) .
- the shield 62 is retracted, and the tabs 66 engage the center mandrel 60.
- the tabs 66 inserted in the aperture 68 may be sufficient, or an additional ridge (74 of FIG. 7) on the center mandrel walls may be included to catch the ends of the legs 64 as they move upward out of the insertion port 36. This is shown in FIG. IOC.
- FIG. 10D the center mandrel 60 and shield 62 are removed. The tabs 66 pull th center mandrel 60 out of the cap 34 through the insertion port 36.
- the shield 62 may be made from stainless steel, plastic, or other material capable of being sterilized.
- the shield and the center mandrel may be manufactured from biocompatible or bioinert material generally commercially available.
- the device 10c includes both an inner flushing duct 82 and outer cell chamber tubes 84,
- the outer tube 84 may be prepared using hollow fiber extrusion technology, generally known to those skilled in the art.
- the inner duct 82 can be of any appropriate material manufactured by any appropriate method. Inner tube centering is accomplished thrugh placement of inter-fitting cap 34 and tip 88 portions at either end of the device 10c.
- the coaxial device 10c includes a cap 34 and cell chamber 20 similar to the other embodiments described in detail above.
- a flushing duct 84 for carrying and flushing exhausted or used solution.
- the bottom portion of the duct is open to a vessel 86 wherein exhausted cell solution is routed up through the flushing duct and out of the device.
- FIGS. 11A-11C includes a tip portion 88.
- the tip 88 includes vessel 86, and serves the additional function of assisting in aligning the cell chamber walls 82 with respect to the center flushing duct 84 during construction of the device 10c.
- refilling solution is introduced into the cell chamber walls 82 through the refilling ports 22.
- the solution flows through the cell chamber 20 and into the vessel 86 at the tip of the device.
- Old solution such as depleted cell suspension solution, is forced out of the chamber 20 and up through the center flushing duct 84, where it is expelled through the expulsion port 23.
- a fill/flush tube 90 may be adapted to fit with the tube sleeve 50.
- a plug 38 covers the ports.
- the tube sleeve 50 is threaded on the outer surface to secure it into position either in a plate mount or directly to the skull.
- the tube sleeve 50 may also have a threaded inner surface for securing a plug 38 having complementary threads, as shown in FIG. 12.
- the fill/flush tube 90 includes a fill duct 92 through which replenishing solution, such as new cell solution or culture medium, flows.
- the tube 90 further includes one or more fill ports 96 which align with the filling ports 22 of the device 10c to enable passage of fluid therethrough.
- the fill/flush tube 90 further includes a flush duct 94 which, in one embodiment, is along the central axis of tube 90.
- the flush duct includes a flush port 98 which aligns with the insertion port 36 of the device 10c.
- the device 10c may further include center tube support fins 100 which stabilize the position of the fill/flush tube 50 when it is positioned at the ports of the device 10c.
- center tube support fins 100 which stabilize the position of the fill/flush tube 50 when it is positioned at the ports of the device 10c.
- Other methods and devices for securing and stabilizing the fill/flush tube 50 may be used, and are known in the art.
- the refill/flush capabilities of the current invention also allow the 5 introduction of therapeutic medicaments or other biologically active factors prior to the cell chambers without removal of the chambers contents.
- the device lOd may include a filter basket 110 with a delivery sheath 112.
- the filter basket 110 is manufactured from a biocompatible micro-filter material generally commercially available. It may be sealed at the 15 proximal end, and attached to an upper portion 114. Due to the problem of movement between the skull and the brain, discussed in further detail above, it is desirable that the upper section 114 be flexible to accommodate such movement.
- the upper portion 114 may 20 be topped with a retaining screw 116, or other securing device.
- the filter basket 110 may be adapted to contain a membrane implant device
- the implant device 120 which enables constant, controlled flow of biologically active factors from the inner cell chamber, out into the desired treatment site.
- the implant device 120 may be a tethered cell chamber, as described above, or other device for containing 0 biologically active factors.
- the illustrated device is replenishable by removing the retaining screw 116, or other plug or cap, and lifting the membrane implant device 120 or other cell chamber, out of the filter basket 110. 5
- the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU23054/92A AU654385B2 (en) | 1991-06-28 | 1992-06-25 | Renewable neural implant device and method |
KR1019930704067A KR940701286A (en) | 1991-06-28 | 1992-06-25 | Regenerative nervous system insert and how to use it |
EP92914757A EP0766576A1 (en) | 1991-06-28 | 1992-06-25 | Renewable neural implant device |
JP5501672A JPH07500260A (en) | 1991-06-28 | 1992-06-25 | Replenishable nerve implant device and method |
NO934843A NO934843L (en) | 1991-06-28 | 1993-12-27 | Renewable neural implant |
FI935871A FI935871A (en) | 1991-06-28 | 1993-12-27 | UTBYTBAR IMPLANTERBAR NEURAL ANORDNING SAMT FOERFARANDE |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US72295091A | 1991-06-28 | 1991-06-28 | |
US722,950 | 1991-06-28 |
Publications (1)
Publication Number | Publication Date |
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WO1993000128A1 true WO1993000128A1 (en) | 1993-01-07 |
Family
ID=24904128
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1992/005389 WO1993000128A1 (en) | 1991-06-28 | 1992-06-25 | Renewable neural implant device and method |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0766576A1 (en) |
JP (1) | JPH07500260A (en) |
KR (1) | KR940701286A (en) |
AU (1) | AU654385B2 (en) |
CA (1) | CA2111978A1 (en) |
FI (1) | FI935871A (en) |
SG (1) | SG48792A1 (en) |
WO (1) | WO1993000128A1 (en) |
Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994018906A1 (en) * | 1993-02-18 | 1994-09-01 | New England Deaconess Hospital, Corp. | Implantable artificial organ |
EP0650377A1 (en) * | 1992-07-13 | 1995-05-03 | Brown University Research Foundation | Implanting devices for release of neuroinhibitory compounds |
WO1995018584A1 (en) * | 1994-01-11 | 1995-07-13 | Baxter International Inc. | Method for implanting tissue in a host |
WO1996033766A1 (en) * | 1995-04-28 | 1996-10-31 | Medtronic, Inc. | Securing device for intercranial infusion port with filter and catheter |
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FR2735032A1 (en) * | 1995-06-07 | 1996-12-13 | Gore Hybrid Technologies Inc | IMPLANTABLE CONTAINMENT APPARATUS FOR A THERAPEUTIC DEVICE AND METHOD FOR LOADING AND RECHARGING THE DEVICE THEREIN |
US5618531A (en) * | 1990-10-19 | 1997-04-08 | New York University | Method for increasing the viability of cells which are administered to the brain or spinal cord |
EP0788351A1 (en) * | 1994-11-10 | 1997-08-13 | The University of Kentucky Research Foundation | Implantable refillable controlled release device to deliver drugs directly to an internal portion of the body |
US5773286A (en) * | 1987-11-17 | 1998-06-30 | Cytotherapeutics, Inc. | Inner supported biocompatible cell capsules |
US5776747A (en) * | 1994-07-20 | 1998-07-07 | Cytotherapeutics, Inc. | Method for controlling the distribution of cells within a bioartificial organ using polycthylene oxide-poly (dimethylsiloxane) copolymer |
US5786216A (en) * | 1987-11-17 | 1998-07-28 | Cytotherapeutics, Inc. | Inner-supported, biocompatible cell capsules |
US5798113A (en) * | 1991-04-25 | 1998-08-25 | Brown University Research Foundation | Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products |
US5800829A (en) * | 1991-04-25 | 1998-09-01 | Brown University Research Foundation | Methods for coextruding immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core |
US5843431A (en) * | 1994-07-20 | 1998-12-01 | Cytotherapeutics, Inc. | Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation |
US6054142A (en) * | 1996-08-01 | 2000-04-25 | Cyto Therapeutics, Inc. | Biocompatible devices with foam scaffolds |
US6495364B2 (en) * | 1995-05-23 | 2002-12-17 | Neurotech, S.A. | Mx-1 conditionally immortalized cells |
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US7820195B2 (en) | 2005-12-30 | 2010-10-26 | Neurotech Usa, Inc. | Micronized device for the delivery of biologically active molecules and methods of use thereof |
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US8961791B2 (en) | 2008-02-13 | 2015-02-24 | Probe Scientific Limited | Molecular exchange device |
WO2018089401A1 (en) * | 2016-11-08 | 2018-05-17 | W.L. Gore & Associates, Inc. | Implantable apparatus for retention of biological moieties |
EP3398559A1 (en) * | 2013-03-07 | 2018-11-07 | ViaCyte, Inc. | 3-dimensional large capacity cell encapsulation device assembly |
US10195140B2 (en) | 2015-05-27 | 2019-02-05 | Neurotech Usa, Inc. | Use of encapsulated cell therapy for treatment of ophthalmic disorders |
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Families Citing this family (1)
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JP2010252924A (en) * | 2009-04-22 | 2010-11-11 | Olympus Corp | Catheter and medication administering device |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4378016A (en) * | 1981-07-15 | 1983-03-29 | Biotek, Inc. | Artificial endocrine gland containing hormone-producing cells |
GB2130916A (en) * | 1982-12-01 | 1984-06-13 | Carl Urban Ungerstedt | Dialysis probe |
WO1988010103A1 (en) * | 1987-06-18 | 1988-12-29 | Gaskill Harold V Iii | An intravascular artificial organ |
WO1990015637A2 (en) * | 1989-06-21 | 1990-12-27 | Brown University Research Foundation | Neurological therapy system |
-
1992
- 1992-06-25 WO PCT/US1992/005389 patent/WO1993000128A1/en not_active Application Discontinuation
- 1992-06-25 CA CA002111978A patent/CA2111978A1/en not_active Abandoned
- 1992-06-25 KR KR1019930704067A patent/KR940701286A/en not_active Application Discontinuation
- 1992-06-25 JP JP5501672A patent/JPH07500260A/en active Pending
- 1992-06-25 AU AU23054/92A patent/AU654385B2/en not_active Ceased
- 1992-06-25 SG SG1996001702A patent/SG48792A1/en unknown
- 1992-06-25 EP EP92914757A patent/EP0766576A1/en not_active Withdrawn
-
1993
- 1993-12-27 FI FI935871A patent/FI935871A/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4378016A (en) * | 1981-07-15 | 1983-03-29 | Biotek, Inc. | Artificial endocrine gland containing hormone-producing cells |
GB2130916A (en) * | 1982-12-01 | 1984-06-13 | Carl Urban Ungerstedt | Dialysis probe |
WO1988010103A1 (en) * | 1987-06-18 | 1988-12-29 | Gaskill Harold V Iii | An intravascular artificial organ |
WO1990015637A2 (en) * | 1989-06-21 | 1990-12-27 | Brown University Research Foundation | Neurological therapy system |
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US5786216A (en) * | 1987-11-17 | 1998-07-28 | Cytotherapeutics, Inc. | Inner-supported, biocompatible cell capsules |
US5773286A (en) * | 1987-11-17 | 1998-06-30 | Cytotherapeutics, Inc. | Inner supported biocompatible cell capsules |
US5618531A (en) * | 1990-10-19 | 1997-04-08 | New York University | Method for increasing the viability of cells which are administered to the brain or spinal cord |
US6264943B1 (en) | 1990-10-19 | 2001-07-24 | New York University | Method for transplanting cells into the brain and therapeutic uses therefor |
US6060048A (en) * | 1990-10-19 | 2000-05-09 | New York University | Method for transplanting cells into the brain and therapeutic uses therefor |
US5750103A (en) * | 1990-10-19 | 1998-05-12 | The New York University Medical Center | Method for transplanting cells into the brain and therapeutic uses therefor |
US5871767A (en) * | 1991-04-25 | 1999-02-16 | Brown University Research Foundation | Methods for treatment or prevention of neurodegenerative conditions using immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core |
US5798113A (en) * | 1991-04-25 | 1998-08-25 | Brown University Research Foundation | Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products |
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US5800829A (en) * | 1991-04-25 | 1998-09-01 | Brown University Research Foundation | Methods for coextruding immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core |
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EP0650377A4 (en) * | 1992-07-13 | 1997-05-21 | Univ Brown Res Found | Implanting devices for release of neuroinhibitory compounds. |
WO1994018906A1 (en) * | 1993-02-18 | 1994-09-01 | New England Deaconess Hospital, Corp. | Implantable artificial organ |
WO1995018584A1 (en) * | 1994-01-11 | 1995-07-13 | Baxter International Inc. | Method for implanting tissue in a host |
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US5795790A (en) * | 1994-07-20 | 1998-08-18 | Cytotherapeutics, Inc. | Method for controlling proliferation and differentiation of cells encapsulated within bioartificial organs |
US6392118B1 (en) | 1994-07-20 | 2002-05-21 | Neurotech S.A. | Mx-1 conditionally immortalized cells |
US5776747A (en) * | 1994-07-20 | 1998-07-07 | Cytotherapeutics, Inc. | Method for controlling the distribution of cells within a bioartificial organ using polycthylene oxide-poly (dimethylsiloxane) copolymer |
US5833979A (en) * | 1994-07-20 | 1998-11-10 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
US5935849A (en) * | 1994-07-20 | 1999-08-10 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
US5840576A (en) * | 1994-07-20 | 1998-11-24 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
US5858747A (en) * | 1994-07-20 | 1999-01-12 | Cytotherapeutics, Inc. | Control of cell growth in a bioartificial organ with extracellular matrix coated microcarriers |
US5843431A (en) * | 1994-07-20 | 1998-12-01 | Cytotherapeutics, Inc. | Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation |
US5853717A (en) * | 1994-07-20 | 1998-12-29 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
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US6495364B2 (en) * | 1995-05-23 | 2002-12-17 | Neurotech, S.A. | Mx-1 conditionally immortalized cells |
US6471687B2 (en) | 1995-06-07 | 2002-10-29 | Gore Enterprise Holdings, Inc. | Implantable containment apparatus for a therapeutical device |
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US5913998A (en) * | 1995-06-07 | 1999-06-22 | Gore Hybrid Technologies, Inc. | Method of making an implantable containment apparatus for a therapeutical device |
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Also Published As
Publication number | Publication date |
---|---|
EP0766576A1 (en) | 1997-04-09 |
FI935871A0 (en) | 1993-12-27 |
SG48792A1 (en) | 1998-05-18 |
JPH07500260A (en) | 1995-01-12 |
CA2111978A1 (en) | 1993-01-07 |
AU654385B2 (en) | 1994-11-03 |
AU2305492A (en) | 1993-01-25 |
KR940701286A (en) | 1994-05-28 |
FI935871A (en) | 1993-12-27 |
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