JP2004512078A - Methods and devices for treating pseudoarthritis - Google Patents

Abstract

Methods, devices and kits for treating spinal pseudoarthritis are provided. In one embodiment, the method comprises providing an effective amount of an osteoinductive composition having an injectable osteoinductive composition comprising an injectable osteoinductive composition in a pharmaceutically acceptable carrier. Feeding to the pseudoarthritis location. In another embodiment, a cannulated drill 10, 10 ', 10 "including a drill and syringe 60, 60', the syringe having a distal end mateably engaged with a proximal end of the drill, and a surgical instrument assembly. 50, 50 'are provided. Drills and other instruments, instrument assemblies, and kits formed therefrom can be advantageously used in methods of treating pseudoarthritis.

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates generally to methods and devices for treating pseudoarthritis.
[0002]
Back pain affects millions of people and is a common cause of physical dysfunction in the middle-aged working population. Many causes of back pain are ruptured or degenerated discs. Often, the only way out of the symptoms of these conditions is discectomy, ie, surgical removal of all or a portion of the disc. In addition, the height of the disc space must be maintained or restored.
[0003]
One strategy to stabilize the incised disc space is to fuse adjacent vertebrae between their respective end plates. Typically, a spacer or implant is inserted into the treated or prepared disc space until complete arthrodesis is achieved. The spacer / implant must provide temporary support and allow for bone ingrowth. Successful discectomy and fusion procedures require the growth or bone bridge adjacent to the bone to form a solid mass between the vertebrae and resist compression loads on the spine during the life of the patient. Parts need to occur.
[0004]
Several metal spacers have been developed to fill the void created by discectomy and promote fusion. Sofamor Danek, Inc. (Memphis, TN) sells a number of hollow spine cages, and a wide variety of other cages are known in the art. . For example, U.S. Pat. Nos. 5,015,247 and 5,984,967 to Michelson et al. And Zdebrick et al. Each disclose a threaded spine cage. These cages are hollow and can be filled with osteoinductive materials such as autografts and allografts before insertion into the disc space. An opening defined in the cage communicates with the hollow interior and provides a path for tissue to grow between the vertebral endplates.
[0005]
Although spinal fusion has generally been somewhat successful with respect to vertebral body fusion or transverse process fusion, the incidence of pseudoarthrosis, also known as pseudoarthritis, or failure of spinal fusion, is limited to certain circumstances. Relatively high. For example, the incidence of pseudoarthritis has been reported to be as high as 40% for smokers and those with multiple positional fusion and asymptomatic metabolic disorders. Pseudoarthrosis has been found to be the cause of the condition in 78% of patients with a condition requiring reoperation, and the success rate decreases with each reoperation. In addition, at least about 90% of attempts to fuse the posterolateral transverse processes by autologous iliac bone grafting in Lewis rats have failed.
[0006]
In order to treat symptomatic pseudoarthritis, conventional open surgical methods expose the fusion mass, exfoliate, re-implant the bone, and replace the new graft and / or new dressing. Including attaching or adding. The repair procedure is extremely cumbersome, highly invasive, and if fusion fails, additional posterior fusion procedures may be required to stabilize the spine. Thus, there is a need for simpler, less invasive methods of treating spinal pseudoarthritis.
[0007]
Summary of the Invention
Applying an osteoinductive composition to a site of pseudoarthritis, such as spinal pseudoarthritis, has been found to be effective in promoting bone growth to treat pseudoarthritis. Accordingly, in one aspect of the present invention, there is provided a method of treating spinal pseudoarthritis.
[0008]
In one form of the invention, the method includes providing an effective amount of an osteoinductive composition to a pseudoarthritis location. Preferably, the osteoinductive composition will be combined with an acceptable carrier, such as a carrier comprising calcium phosphate. The osteoinductive composition is effective in promoting bone growth to treat spinal pseudoarthritis.
[0009]
In a preferred form, the method includes advancing the first elongate member to a location of a spinal pseudoarthrosis in the patient. The first elongated member has a proximal end, a distal end, and a lumen extending longitudinally therethrough. The method includes advancing the osteoinductive composition described herein through the lumen of the first elongate member. In another preferred embodiment of the present invention, the osteoinductive composition is advanced through the lumen of the elongate member to the pseudoarthritis mass, into and across the pseudoarthritis mass. And stretch it.
[0010]
The methods described herein can be performed with or without peeling, and can be performed without removing the implant if intervertebral fusion fails. Furthermore, these methods can use minimally invasive surgical methods that can significantly reduce the morbidity associated with surgery, reduce hospital stays and reduce patient recovery time.
[0011]
In another aspect of the present invention, a surgical instrument is provided. Preferably, these devices are configured for use in the methods for treating spinal pseudoarthritis described herein. In one form of the invention, a cannulated drill is provided that includes an elongated member having a proximal end, a distal end, an inner surface, and an outer surface. The inner surface defines a lumen extending along the length of the elongate member and is sized to receive the elongate obturator. The distal end of the elongate member has at least one bone cutting edge. The proximal end of the elongated member has a connector configured to mateably engage the distal end of the syringe with the proximal end of the elongated member. Preferably, the elongate member is made of a biocompatible material.
[0012]
Also provided is a surgical instrument assembly that includes at least the cannulated drill described herein and a syringe. The syringe defines a cavity and includes a housing having a proximal end and a distal end. The distal end of the syringe mateably engages the proximal end of the elongate member. When the distal end of the syringe and the proximal end of the elongated member are matingly engaged, the lumen of the elongated member and the cavity of the housing are in fluid communication.
[0013]
DESCRIPTION OF THE EMBODIMENTS
For the purpose of promoting an understanding of the principles of the invention, embodiments will now be described, and specific terms will be used for the description. However, this is not intended to limit the scope of the invention in any way.Modifications and further modifications of the invention, and further applications of the principles of the invention described herein, It will normally be devised by those skilled in the art to which the invention pertains.
[0014]
The present invention relates to methods and devices for treating pseudoarthritis. Pseudoarthrosis, also known as pseudoarthrosis, refers to a condition resulting from an incomplete bone fusion process. For pseudoarthrosis of the spine, this includes the failure of adjacent vertebrae to fuse, ie, the presence of some other bone discontinuities within the fusion mass. That is, the bones of the spinal fusion are not contiguous, so there are non-uniformities or voids between the bones. In a first aspect of the invention, embodiments of these methods include providing an effective amount of an osteoinductive composition to a spinal pseudoarthritis location. Preferably, the composition comprises an osteoinductive factor, such as in a pharmaceutically acceptable carrier. The osteoinductive composition is effective in promoting bone growth to treat spinal pseudoarthritis.
[0015]
In a second aspect of the present invention, an embodiment of a surgical instrument is provided. In one form, a surgical instrument is made of a biocompatible material and includes a cannulated drill that includes an elongated member having a proximal end, a distal end, an inner surface, and an outer surface. The inner surface defines a lumen extending along the length of the elongate member, the lumen being sized to receive an elongate embolus. The distal end of the elongate member has at least one bone cutting edge. The proximal end of the elongate member has or defines a connector configured to mateably engage the distal end of the syringe. Also provided is an embodiment of a surgical instrument assembly including a drill and a syringe as described herein. Additionally or alternatively, the surgical assembly can include a cannulated drill and an obturator slidably engaging within an interior region of the cannulated drill. One or more surgical assemblies can be provided to deliver the flowable or injectable osteoinductive composition to the desired treatment site. Also provided is an embodiment of a kit for treating pseudoarthritis comprising a combination of the surgical instruments and / or instrument assemblies described herein.
[0016]
As disclosed above, in one aspect of the present invention, a surgical instrument may be preferably utilized in a method for treating pseudoarthritis. Embodiments of these devices will be described first so as to facilitate description of a method for treating spinal pseudoarthritis. In one embodiment, the surgical instrument has a member that defines and supplies an elongated passage, such as the drill 10 of FIGS. Drill 10 includes an elongated member 20 having a proximal end 21, a distal end 22, an outer surface 23, and an inner surface 24. The distal end 22 has at least one bone cutting blade 26, preferably about 2 to 4 cutting blades, for cutting bone. Alternatively, the drill can have any device capable of forming a passage or channel adjacent to or at the site of pseudoarthritis, such as a drilling device, a milling device, or the like.
[0017]
Inner surface 24 typically defines a lumen 25 that extends along the length of elongate member 20 from proximal end 21 to distal end 22. Lumen 25 has a first opening 11 adjacent proximal end 21 and a second opening 12 adjacent distal end 22 and is illustrated as a cylindrical passage allowing access to the interior of drill 10. Have been. Further, the lumen 25 of the elongate member 20 is sized to receive an emboli (not shown). In another embodiment, lumen 25 is sized to accept a guidewire, such as a Kwire. The guidewire can be selected to have any desired diameter and / or length. The guidewire can be inserted into the treatment site to facilitate the desired placement of the drill 10 during treatment.
[0018]
The proximal end 21 of the elongate member 20 is preferably configured to fit with a syringe. Proximal end 21 of elongate member 20 can have or define a connector 27 that mates and engages the distal end of the syringe with proximal end 21 of elongate member 20. The connector can be formed integrally with the elongate member or separately connected to the elongate member, such as by using a push-fit connector, an adhesive and any other fastening method or combination thereof. A wide variety of connectors are available, including luer lock connectors, moose taper connectors, and snap lock connectors.
[0019]
FIG. 3 illustrates one alternative embodiment of a drill 10 'used in the present invention. Drill 10 'is formed similarly to drill 10, and like reference numerals are used with like reference numerals to indicate like components. The drill 10 'has a plurality of openings 28 extending through an outer surface 23' to an inner surface 24 '. Preferably, openings 28 are provided in the desired size, number and location along the length of drill 10 '. In one embodiment, the openings are sized and positioned so that osteoinductive material can be effectively placed over the pseudoarthritis region of the spine such that minimal or no drill repositioning is required. Are located in In the illustrated embodiment, a plurality of openings 28 are located proximate the distal end 22 '.
[0020]
Referring now to FIGS. 4 and 5, one embodiment of a lumen blocking device, such as an obturator 30, includes an elongated member having a proximal end 41, a distal end 42, an outer surface 43, and an inner surface 44. 40. Inner surface 44 typically defines a lumen 45 that extends along the length of elongate member 40 from proximal end 41 to distal end 42. The obturator 30 is designed and configured to conform to the inner surface 24 of the elongate member 20 of the drill 10 and / or 10 'and / or to be slidably received within the lumen 25 and / or 25'. Is preferred. The embolus 30 can be of various shapes, but in one form of the invention, the embolus 30 is cylindrical. For example, the obturator 30 is slidably disposed within the lumen 20 of the drill 10 so as to provide an assembly 35 as best illustrated in FIGS. 6A and 6B. The obturator 30 can be sized and configured to prevent material from entering the lumen of the drill during the drilling process.
[0021]
Still other drills can be utilized in other aspects of the invention. Referring to FIG. 7, a drill 10 '' is shown. Drill 10 '' is formed similarly to drill 10, and like reference numbers are used with double primed numbers to indicate like elements. The drill 10 '' preferably has a built-in depth gauge 29. The depth gauge 29 can be movably secured to a portion of the surface 23 '' that limits the drilling depth of the drill 10 ''. Depth gauge 29 is positionable during a surgical procedure. For example, a surgeon can use x-ray, computed tomography (CT), fluoroscopy or other techniques to determine the desired depth of a bone or pseudoarthritis site hole. The surgeon can then measure the distance from the distal end 26 "to the proximal end 21", which is equal to the desired hole depth. The surgeon can then place the depth gauge 29 at a position 36 from the end of the drill 10 '' equal to the desired hole depth. Depth gauge 29 can be secured in a desired location using a set screw or other locking mechanism.
[0022]
The drills and emboli described herein can be formed from biocompatible materials. In a preferred form of the invention, the drill and the obturator can be formed of a metal material including stainless steel, titanium and its alloys. Other suitable materials include nitinol or other shape memory materials.
[0023]
In another aspect of the present invention, an embodiment of a surgical instrument assembly is provided. Referring now to FIG. 8A, in one form of the invention, surgical instrument assembly 50 includes drill 10 and syringe 60. Although a drill 10 is shown, it is understood that the assembly may include any drill 10, 10 'and / or 10''. Syringe 60 can be any device capable of delivering an osteoinductive composition.
[0024]
In one embodiment, syringe 60 includes a barrel or housing 61 having a proximal end 62 and a distal end 63. Housing 61 defines a cavity or chamber 64 that holds the composition to be dispensed. A plunger 66 having a plunger head 67 is located within the cavity 64 of the syringe 60. The distal end 63 defines a connector portion 68 such as a luer lock connector provided to releasably engage the connector 27 of the drill 10.
[0025]
With further reference to FIG. 8B, the distal end 63 of the syringe 60 is matingly engaged with the proximal end 21 of the drill 10. When so engaged, chamber 64 of syringe 60 is in fluid communication with lumen 25 of drill 10 to form surgical instrument assembly 50. Syringe 60 should be formed of a material that does not react with the osteoinductive composition, such as metal, polymeric materials including glass, and synthetic polymers such as polyalkenes, including polyethylene, polypropylene, poly (vinyl chloride) and polystyrene. Can be.
[0026]
Referring to FIG. 8C, one alternative surgical instrument assembly having a drill 10 and a syringe 60 'is illustrated. As mentioned above, the drill 10 is shown in the assembly 50 ', but any drill 10, 10', 10 '' can be combined with the syringe 60 '. Syringe 60 'is formed similarly to syringe 60, such that like reference numbers indicate like components but are primed. Plunger 66 ′ has one or more threads 68 that extend along the length of plunger shaft 69. The threads 68 may facilitate the incremental adjustment of the plunger 66 within the chamber 64 and thus facilitate the introduction of material into or out of the chamber 64.
[0027]
As shown in FIG. 9, in another embodiment, an elongate delivery member 70 fluidly connectable to an osteoinductive material delivery device includes a proximal end 72, a distal end 73, an outer surface 74, an inner surface 75. Is provided. Inner surface 75 typically defines a lumen 76 that extends along the length of elongate member 71 from proximal end 72 to distal end 73. In one embodiment, the end 73 can be closed. Alternatively, distal end 73 may have one or more openings extending therethrough in communication with lumen 76. Further, the elongate member 71 has a plurality of openings or other openings or hole portions 78 extending through the outer surface 74 anywhere along the length of the elongate member 71, such as adjacent the distal end 73. Can be. Proximal end 72 may have a connector 77 for matingly engaging with a syringe, and may be similar to connector 27 as described above with respect to drill 10.
[0028]
In another aspect, the invention provides a method of treating pseudoarthritis. These methods can be minimally invasive. For example, an incision is made within about 30 mm in length to substantially reduce exposure of body components. In such a manner, the cannula can be inserted into the body, through which necessary tools can be supplied and manipulated at the surgical site. Thus, these methods can be performed transdermally. Although these methods can be used to treat a wide variety of pseudoarthritis involving heterogeneous portions of long bones, these methods are useful for spinal pseudoarthritis, especially for damaged or affected spinal discs. It is preferably used to treat spinal pseudoarthritis at a transverse process fusion site, such as a location or a transverse process fusion site.
[0029]
In one embodiment of the invention, the method of treatment comprises providing an effective amount of an osteoinductive composition to a desired location in proximity to spinal pseudoarthritis. The osteoinductive composition is injected or otherwise introduced in proximity to or directly into the pseudoarthritis mass.
[0030]
As defined herein, a pseudoarthritis mass is a portion of a bone or a fragment thereof that is completely interconnected to provide or connect the desired bone mass to adjacent bone as desired. Is a collection of tissues found at the site of pseudoarthritis, including those that are not integrated into the. Portions of bone and / or debris can be diffused or otherwise dispersed within the fibrous tissue. Additionally or alternatively, the bone mass may include undesirable discontinuities. In addition, the pseudoarthritis mass may include a single bone mass with undesirable cracks or voids extending thereover. That is, the bone cannot be continuous from one end or side of the pseudoarthritis mass to the other end or side as desired.
[0031]
Passages, bone holes or other spaces are formed in the bone adjacent to the pseudoarthritis mass. Drilling into the pseudoarthritis area will form some hemorrhagic bone and release osteogenic cells that can respond to the presence of bone morphogenic protein (BMP). These bone forming cells or stem cells become osteoblasts by BMP, and the osteoblasts continue bone formation.
[0032]
In addition, after the bone hole has been formed, the osteoinductive composition may be placed in the passageway across the non-uniform portion and across the non-uniform portion, or across the discontinuous cracks and / or voids in the bone. Can be injected. That is, after the injection, the osteoinductive composition may pass through the mass of fibrous tissue from a passageway or other space formed in the bone at one side of the pseudoarthritis mass. It extends into passages or other spaces formed in opposing or opposite bones of the tissue.
[0033]
Without being limited by theory, it is believed that the osteoinductive composition is released into fibrous tissue and bone mass, resulting in the formation of new bone. The osteoinductive composition then causes an initial osteodisruptive resorption, followed by germination of new bone formation within and / or adjacent to the injection area. Thus, the osteoinductive composition can cause ossification of soft tissue, such as scars or other tissue, where the fusion has failed. Once a solid connection has been formed over the pseudoarthritis mass, allowing the bone at that point to be substantially continuous, the new bone and the original bone are renewed. It is further believed that the modified loading environment will continue to be modified and more robust, thereby accommodating new loads.
[0034]
When performing these methods, the heterogeneous area of the pseudoarthritis mass is first located by computer tomography (CT). The non-uniformities are visible as radiopaque regions representing fibrous tissue. In pseudoarthritis at an intervertebral fusion point, the radiopaque region is often visible at the interface between the intervertebral spacer or fusion cage and the adjacent vertebral body.
[0035]
In another aspect of the invention, a kit for treating spinal pseudoarthritis is provided. Embodiments of the kit may include one or more drills 10, 10 ', 10 ", syringes 60, 60', emboli 30, and / or as described herein. And a supply member 70. Preferably, drills 10, 10 ', 10 ", syringes 60, 60' and / or emboli 70 are provided such that they can engage one another to form one or more surgical assemblies. Shall be Additionally or alternatively, the kit can include a drill, syringe, embolus, and therapeutic guidewire that do not engage with each other. Further, the kit can include an obturator, a syringe, an elongate supply member, and a cannulated drill having a proximal end without a connector.
[0036]
Referring now to FIGS. 10A and 10B, a pseudoarthritis mass or defect 85 adjacent to bone tissue B is represented by a vertebra V ₁ , V ₂ Lateral process T ₁ , T ₂ Are visually recognized as poorly connected portions of the lateral projections. In one embodiment of treating this spinal pseudoarthrosis, a K-wire 80 or similar other guide wire having a sharp or other sharp or piercing end 81 is displaced under fluoroscopic guidance. It is inserted percutaneously through the skin surface S and bone adjacent to the area of the portion or pseudoarthrosis mass 85, through the heterogeneous portion, and into the bone opposite the non-uniform portion, as shown in FIG. 10B. In this manner, the K wire 80 can pass from the bone tissue on one side of the pseudoarticular mass 85 to the defect or fibrous tissue through the pseudoarthritis mass defect or fibrous tissue. Extends into the bone on the opposite side of the bone. The placement of the wire 80 can be monitored during surgery using CT, fluoroscopy, or other techniques.
[0037]
Next, referring to FIGS. 11-14, an incision 86 is made in the outer tissue layer. Incision 86 allows for immediate placement and positioning of cannula 90. The incision 86 may be small and minimally invasive enough to reduce disruption of adjacent tissue, minimize patient discomfort, and facilitate rapid patient recovery.
[0038]
The distal end 92 of the cannula 90 is advanced along the K-wire 80 through an incision 86 adjacent the selected treatment site. The cannula can have a rounded end to facilitate insertion of the cannula and reduce complications that may occur during the insertion, such as tissue damage. A cannulated drill, such as drill 10, disposed within the luminal embolus 30 then passes from the proximal end 91 of the cannula 90 along the K-wire 80 through the lumen 93 of the cannula 90 to allow for spinal pseudoarthritis. Advance to the position selected for treatment and to a position adjacent the distal end 92 of the cannula 90 as shown in FIG.
[0039]
Next, the emboli 30 advances the drill placed within the lumen and cuts the bone adjacent to the pseudoarthritis mass 85 as desired. As shown in FIG. 13, at least one hole is drilled through the uneven portion to the opposite side of the uneven portion. The method creates at least one passage 95 or other space for placement of the osteoinductive composition. At this point, if desired, the K wire 80 can be removed. Next, as shown in FIG. 14, the embolus 30 can be removed from the lumen 25 of the drill 10, in which case the K wire 80 has also been removed. The distal end 62 of the syringe 60 can then be matingly engaged or fluidly connected to the proximal end 21 of the drill 10, as shown in FIG. Syringe 50 is preferably filled with a desired amount of osteoinductive composition 96. An assembly of syringe 60 and drill 10 can be used to deliver osteogenic material to the site of pseudoarthritis.
[0040]
Referring now to FIG. 16, the plunger 66 is pushed to deliver the osteoinductive composition 96 under pressure into the passageway or space 95 and into at least a portion of the pseudoarthritis mass 85 while pulling the drill 10. It can, but need not, be pushed back out of the nest or passage. It should be understood that the drill 10 ′ or 10 ″ can be used in the assembly and method described herein. When utilizing such a drill having an opening along the length of the drill, the osteoinductive material is supplied to the fibrous tissue of the pseudoarthritis mass 85 and the fibrous tissue is proximate to the pseudoarthritis site. It is preferred to be deviated or arranged throughout the location. It is contemplated that it is also possible to inject the osteoinductive composition under pressure using a syringe with a screw-driven or ratchet-type mechanism. In one embodiment, a drill 10 'or delivery member 70 having an opening along the length of the drill or delivery member can be utilized to deliver osteoinductive material to the site of pseudoarthritis. The drill 10 'or delivery member 70 can be arranged as follows: the formed opening 28 or 78 is adjacent to the pseudoarthritis defect, passage 95 and / or a pseudoarthritis mass or The entire area can be straddled so that the osteoinductive material can be effectively placed throughout the mass with minimal or no repositioning of the drill or delivery member. When utilizing the drill 10 ', if the opening is narrowed or clogged by cells or other debris, the lumen of the drill 10' is washed with a biocompatible solution, such as a saline solution, and the drill 10 ' It is understood that debris can be removed under pressure through the proximal end of '. Further, when utilizing an elongate member having an opening along the length of the member, the guidewire remains in place during delivery of the osteogenic composition, and the composition remains primarily in the surrounding fibrous tissue. Can be supplied.
[0041]
Referring now to FIG. 17, in one alternative embodiment, any one of the drills 10, 10 ', 10 "can be utilized to form the passage 95. The drill 10 or 10 'can be provided with connectors 27, 27' for engaging the syringe, but these connectors need not be provided. After forming one or more holes or passages 95, the drill 10, 10 'or 10''can be partially or completely withdrawn from the treatment site. The syringe can then be connected to the proximal end of the elongate delivery member 70 through which the osteoinductive composition can be delivered.
[0042]
In another aspect, one incision or other insertion point may be made in the skin and only one injection of the osteoinductive composition may be made, but with a drill 10, 10 'or 10''. A plurality of passages 95 or other openings can be formed. Thereafter, a plurality of passages 95 or other spaces may be filled with the osteoinductive composition as described herein. Alternatively, a large incision may be made to completely expose the site of pseudoarthritis.
[0043]
When practicing a method of treating spinal pseudoarthrosis at a fusion point between vertebral bodies, such as a lumbar or cervical fusion point, within an intervertebral spacer or fusion cage and optionally adjacent to the spacer or fusion cage. A similar procedure can be performed including forming a hole or other opening 99.
[0044]
In another embodiment for treating pseudoarthritis, referring to FIGS. 18 and 19, a pseudoarthritis mass 100 is shown at a location within the intervertebral space 98. A drill 10 is operatively positioned within and adjacent to the pseudoarthritis mass within the fusion cage 98 so as to form a passageway or hole 99. In one embodiment, cannulated drill 10 is positioned around K-wire 88 within the lumen of cannula 90 positioned adjacent to pseudoarthritis mass 100. A hole or passage is formed by piercing the pseudoarthritis mass 100 using the drill 10 and piercing the upper (upper) and lower (lower) vertebral regions U, L adjacent the fusion cage 98. You.
[0045]
Although the present invention has been described as a method of treating pseudoarthritis at the fusion of transverse processes, it is understood that the present invention can also be used to treat pseudoarthritis near other bone tissue. Let's do it. For example, limb load bearing or long bones can be treated as preferred according to the present invention. Any pseudoarthritis of different types of bone, long, short, flat and irregular, can be treated according to the present invention. In addition, any animal retaining a skeletal structure, including humans, can be treated according to the present invention.
[0046]
The osteoinductive composition used in the present invention can include an osteoinductive factor in a pharmaceutically acceptable carrier. A wide variety of osteoinductive factors can be used, including growth factors such as bone morphogenetic proteins (BMPs), LIM organic proteins (LMPs) and growth discriminating factors (GDFs). A wide variety of bone morphogenetic proteins are contemplated, including those heterodimers and combinations thereof, including those specified as BMP-2 through BMP-18. Other suitable growth factors include platelet-derived growth factor, insulin-like growth factor, epidermal growth factor, cortical osteoinductive morphogenetic protein, growth discriminating factors such as growth discriminating factor 5, TGF-α, TGF-β. Growth factors or other growth factors with osteoinductive properties. The protein can include a recombinant protein, such as a recombinant human protein. Suitable recombinant human bone morphogenetic proteins (rhBMPs) include rhBMP-2, rhBMP-7, but are derived from any of the other bone morphogenetic proteins described herein, their heterodimers and combinations thereof. You can also.
[0047]
Bone morphogenetic proteins (BMPs) are available from Genetics Institute, Inc., Cambridge, Mass. And can also be made by one of ordinary skill in the art, And are described in the following patents: No. 5,187,076 to Wozney et al., US Pat. No. 5,366,875 to Warsney et al., And US Pat. No. 4,877,864 to Wang et al. U.S. Pat. No. 5,108,922 to Wang et al., U.S. Pat. No. 5,116,738 to Wang et al., U.S. Pat. No. 5,013,649 to Wang et al., U.S. Pat. No. 5,106,748 and International Patent Application WO 93/00432 to Warsney et al., International Patent Application WO 94/26893 to Celeste et al., And International Patent Application WO 94/26892 to Celeste et al. is there. A wide variety of bone morphogenic proteins, whether obtained as described above or sequestered from bone, are contemplated. Methods for sequestering bone morphogenic proteins from bone are described, for example, in U.S. Patent No. 4,294,753 to Urist and in Urist et al., 81 PNAS 371, 1984.
[0048]
The osteoinductive factor can be dispersed in or maintained in a wide variety of carriers. The carrier can be made resorbable. Suitable carriers include water-soluble buffers, collagen, gelatin, polylactic acid, synthetic resorbable polymers such as polyglycolic acid, alternating copolymers of polylactic acid and polyglycolic acid, carboxymethylcellulose, materials containing minerals, hyaluronic acid. Including acids and other glycosaminoglycans and combinations thereof. In a particular form of the invention, the carrier is a resorbable mineral-containing cement, such as a calcium phosphate cement.
[0049]
Such calcium phosphate cements are available from Etex Corporation and are, for example, all to Lee et al., US Pat. No. 5,783,217, US Pat. No. 5,676,976. No. 5,683,461, US Pat. No. 5,650,176 and WO 98/16268, WO 96/39202, and hydroxyapatite as described in WO 98/16209. And a synthetic calcium phosphate comprising poorly or poorly crystalline calcium phosphate, such as low or poorly crystalline phosphorus lime. As defined in the cited patents and herein, a "poor or poorly crystalline" calcium phosphate material is an amorphous and / or nanocrystalline material with little or no long range, Materials that exhibit a predominant crystalline region on the order of nanometers or angstroms are meant. The carrier calcium: phosphate ratio typically ranges from about 0.3 to about 0.7, and in another embodiment, from about 0.4 to about 0.6.
[0050]
The osteoinductive composition comprises nucleotides encoding the respective osteoinductive factors so that the osteoinductive factors can be produced in vivo in a pharmaceutically acceptable carrier or in a pharmaceutically acceptable carrier. It can include a sequence. Thus, a nucleotide sequence can be operably linked to a promoter sequence and inserted into vectors, including plasmid vectors and virus vectors. When arranged in a particular functional relationship with other nucleating acid sequences, a nucleolinic acid sequence is "operably linked" to another nucleolinic acid sequence. In addition, attractable and structural promoters specific to a given cell can be selected based on the surgical environment. In one embodiment, cells, including eukaryotic cells, such as animal cells, are transformed with a nucleotide sequence encoding an osteoinductive factor, and the osteoinductive composition is then pharmaceutically acceptable. The transformed cells can be contained in a suitable carrier. In another aspect, the osteoinductive composition comprises a virus, such as, for example, an adenovirus, capable of manifesting the intercellular production of LIM organic protein.
[0051]
Components that maintain the cells within the resorbable cement carrier can be included. Components that maintain cells are those that provide nutrients to cells so that osteoinductive factors can be created. Components that maintain the cells can be selected so as to not substantially alter or otherwise alter the rate at which the carrier is resorbed. Components that maintain such cells include collagen and can utilize a variety of cell media for culturing ex vivo cells, for example, enriched with about 5% human serum albumin (HSA). Includes injectable media such as normal saline, Dulbecco's Modified Eagle's Medium (DMEM), RPMI 1640 enriched with fetal calf serum, or serum-free media formulations such as XVIVO products Or a component includes the combination. In still other embodiments, the nucleotide sequence can be combined directly with the carrier for delivery.
[0052]
The desired amount of osteoinductive factor contained in the carrier and the desired amount applied to the treatment site is typically an amount effective to form new bone to treat spinal pseudoarthritis. . The amount depends on a wide variety of factors, including the osteoinductive potential of the factor, the nature of the carrier and the degree of pseudoarthritis. In one embodiment, for example, the amount is in the range of about 0.5 mg BMP / ml carrier to about 4 mg BMP / ml carrier (BMP: dry carrier in the range of about 1: 2000 to about 1: 250). Weight ratio). A further embodiment of the composition comprises about 1 mg BMP / ml carrier: about 3 mg BMP / ml carrier (equivalent to a BMP: dry carrier weight ratio ranging from about 1: 1000 to about 1: 333). On the other hand, other embodiments include at least about 2 mg of BMP / ml carrier (corresponding to a BMP: dry carrier weight ratio in the range of at least about 1: 500). The amount of osteoinductive composition applied to the fusion site will also depend on the factors described above. For example, in one embodiment, the amount is from about 2 mg to about 40 mg BMP, in another embodiment from about 4 mg to about 20 mg BMP, and in yet another embodiment at least about 12 mg BMP. Sufficient to supply.
[0053]
This procedure can be performed at an intervertebral fusion site that includes a wide variety of implants, such as those having an interior chamber open to the anterior or posterior location. Such implants include those found in U.S. Pat. Nos. 4,961,740, 5,015,247, and 5,423,817, where an anterior or posterior approach is used. No end caps are used to close the chambers of these implants so that they cannot be accessed. The procedures herein can be performed at a location that includes the implant where the end cap has penetrated and the end cap has been removed or the end cap has been removed.
[0054]
While the embodiments of the present invention have been shown and described in detail in the drawings and the above description, this is merely an example, and should not be construed as limiting the features. It is understood that changes and modifications are desired to be protected. Furthermore, all documents cited herein are hereby incorporated by reference in their entirety.
[Brief description of the drawings]
FIG.
1 is a side view of one embodiment of a drill provided in accordance with the present invention.
FIG. 2
FIG. 2 is a first end view of the drill of FIG. 1.
FIG. 3
FIG. 6 is a side view of one alternative embodiment of a drill having a plurality of openings extending along the length of the drill for use with the present invention.
FIG. 4
FIG. 4 is a side view of an elongated embolus used in a drill according to the present invention.
FIG. 5
FIG. 5 is a first end view of the embolus of FIG. 4.
FIG. 6
FIG. 6A is a cutaway side view of an embolus / drill assembly according to the present invention.
6B is a first end view of the embolic / drill assembly of FIG.
FIG. 7
FIG. 4 is a side view of one alternative embodiment of a drill used in the present invention.
FIG. 8
FIG. 8A is an exploded view of a syringe-drill assembly provided in accordance with the present invention.
8B is a side view of the syringe-drill assembly of FIG. 8A.
FIG. 8C is an exploded view of one alternative embodiment of a syringe-drill assembly provided in accordance with the present invention.
FIG. 9
FIG. 4 is a side view of an elongated feed member having an opening extending along the length of the member provided in accordance with the present invention.
FIG. 10
10A is a side view of a pair of vertebrae showing a state of pseudoarthrosis at the fusion point of the transverse process.
10B is a side view of the pseudoarthritis state of the pair of vertebrae of FIG. 10A with the guidewire inserted into the pseudoarthritis mass.
FIG. 11
FIG. 10B is an enlarged view of the pseudoarthritis location of FIG. 10A showing the cannula positioned adjacent to the treatment location.
FIG.
FIG. 12 is a side view of the pseudoarthritis mass of FIG. 11 showing a cannulated drill having an embolus disposed within the lumen.
FIG. 13
FIG. 13 is a side view of FIG. 12 showing the drill in the drill hole of the pseudoarthritis mass.
FIG. 14
FIG. 14 is a side view of the pseudoarthritis mass of FIG. 13 showing a drill without an obturator.
FIG.
FIG. 15 is a side view of the pseudoarthritis mass of FIG. 14 showing a syringe connected to a drill according to the present invention.
FIG.
FIG. 16 is a partially cutaway side view of the pseudoarthritis site of FIG. 15 showing a state in which the osteoinductive composition is supplied into the perforation hole of the pseudoarthritis mass according to the present invention.
FIG.
12 is a side view of the pseudoarthritis mass of FIG. 11 showing a plurality of holes drilled into the mass according to one embodiment of the present invention.
FIG.
FIG. 9 is a partial cross-sectional side view showing a fusion cage between a pair of vertebrae with a drill positioned within a pseudoarthritis mass disposed within the fusion cage according to another embodiment of the present invention.
FIG.
Line 19 in FIG. 18 showing the intervertebral implant between adjacent vertebrae showing a plurality of drill holes drilled into the pseudoarthritis mass in the implant chamber and drilled into the superior vertebral body adjacent to the implant. FIG. 20 is a sectional view along -19.

Claims (38)

In a method of treating pseudoarthritis,
Identifying the location of spinal pseudoarthritis;
To treat the pseudoarthritis, an effective amount of the injectable osteoinductive composition to promote bone growth is delivered to the site of the pseudoarthritis in a pharmaceutically acceptable carrier. The method of treating pseudoarthritis. 2. The method of claim 1, wherein the osteoinductive composition comprises a bone morphogenic protein. 3. The method of claim 2, wherein the bone morphogenic protein is BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, A method selected from the group consisting of BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, a mixture thereof and a heterodimer thereof. 4. The method of claim 3, wherein said bone morphogenetic protein is a recombinant protein. 5. The method of claim 4, wherein said recombinant protein is selected from the group consisting of rhBMP-2, rhBMP-7, a mixture thereof and a hetrodimer. 2. The method of claim 1, wherein the osteoinductive composition comprises an adenovirus capable of stimulating cellular production of a LIM mineralized protein. 7. The method of claim 6, wherein said LIM mineralized protein is LMP-1. The method of claim 1, wherein the carrier is a calcium phosphate cement. 2. The method of claim 1, wherein said carrier comprises resorbable cement, carboxymethylcellulose, polylactic acid, polyglycolic acid, an alternating copolymer of polylactic acid and polyglycolic acid, hyaluronic acid, glycosaminoglycan and mixtures thereof. A method selected from the group. 2. The method of claim 1, wherein delivering the osteoinductive composition advances an elongated member having a proximal end, a distal end, and a lumen extending longitudinally therethrough to the site of the pseudoarthritis. That
Advancing the osteoinductive composition through the lumen of the elongate member to the site of the pseudoarthritis. 11. The method of claim 10, wherein the elongate member is connected to an osteoinductive composition delivery device. The method of claim 10, wherein the elongate member comprises at least one deboning surface. 2. The method of claim 1, further comprising forming at least one passage in the tissue mass at the location of a spinal pseudoarthrosis. 2. The method of claim 1, wherein the location of the pseudoarthritis comprises a mass of pseudoarthritis, forming a passage in bone adjacent to the mass of pseudoarthritis; Supplying the osteoinductive composition to extend from a passageway within the bone on one side of the fibrous tissue of the pseudoarthritis mass into a passageway formed in the bone on the opposite side of the fibrous tissue. The method further comprising: 2. The method of claim 1, wherein the spinal pseudoarthritis location comprises a pseudoarthritis mass, and the pseudoarthritis mass is located at a fusion site between vertebral bodies. 2. The method of claim 1, wherein the pseudoarthritis mass comprises a pseudoarthritis mass, wherein the pseudoarthritis mass is located at a fusion of one or more vertebral body transverse processes. How. 2. The method of claim 1, wherein the pseudoarthritis mass is positioned proximate a fracture. 18. The method of claim 17, wherein the fracture site is at least partially fused. 2. The method of claim 1, wherein the pseudoarthritis mass is positioned proximate to a long bone. In a method of treating spinal pseudoarthritis in a patient,
Advancing a first elongate member having a proximal end, a distal end, and a lumen extending longitudinally therethrough to a spinal pseudoarthrosis location within a patient's body;
Advancing an injectable osteoinductive composition to said position through said first elongate member, wherein said osteoinductive composition comprises an osteoinductive agent in a pharmaceutically acceptable carrier. A method for treating spinal pseudoarthritis in a patient. 21. The method of claim 20, wherein the advancing a first elongate member comprises advancing the first elongate member into a fibrous tissue of a pseudoarthritis mass at the location. 21. The method of claim 20, wherein the first elongate member comprises a distal end having at least one bone cutting edge. 21. The method of claim 20, wherein the first elongate member has a plurality of openings extending along at least a portion of a length of the first elongate member. 21. The method of claim 20, wherein the pseudoarthritis location of the spine comprises a pseudoarthritis mass, forming a passage in bone adjacent to the pseudoarthritis mass, and a pseudoarthritis mass. Providing the osteoinductive composition to extend from an intraosseous passage on one side of the fibrous tissue, through the fibrous tissue, and into a passage formed in the bone opposite the fibrous tissue. The method further comprising: 21. The method of claim 20, wherein
Prior to advancing the first elongate member, a second elongate member having a proximal end, a distal end, a lumen extending longitudinally therethrough, and the distal end having at least one bone cutting edge is provided. Advancing to the spinal column pseudoarthritis position;
Retracting the second elongate member. 26. The method of claim 25, wherein the second elongate member has a plurality of openings extending along a length of the second elongate member. A method of treating spinal pseudoarthritis in a patient's body,
An elongate member having a proximal end, a distal end, and a lumen extending longitudinally therethrough, wherein the distal end of the member has at least one bone cutting edge. Advancing into the mass of
Advancing an osteoinductive composition through the lumen of the elongate member to the pseudoarthritis mass, wherein the osteoinductive composition extends across the pseudoarthritis mass; Comprising an osteoinductive factor in a pharmaceutically acceptable carrier and effective to promote bone growth to treat the spinal pseudoarthritis. How to treat spinal pseudoarthritis. 30. The method of claim 27, wherein the osteoinductive composition comprises cells that have been converted with a nucleotide sequence encoding an osteoinductive factor, wherein the nucleotide sequence is operably connected to an accelerator sequence, whereby A method wherein the osteoinductive factor is produced in vivo. A cannulated drill comprising an elongate member formed of a biocompatible material and having a proximal end, a distal end, an inner surface, and an outer surface, the inner surface defining a lumen, wherein the lumen is the elongate member. Sized to extend along the length of the elongated member and to receive an elongated obturator, the distal end of the elongated member having at least one bone cutting edge, and the proximal end of the elongated member extending the distal end of the syringe into the elongated end of the syringe. A cannulated drill having a connector configured to mateably engage said proximal end of a member. 30. The drill of claim 29, wherein the elongate member is cylindrical. 30. The drill of claim 29, wherein the elongate member is formed from a biocompatible metallic material. 28. The drill of claim 27, further comprising an elongated obturator slidably disposed within the lumen of the elongated member. 28. The drill of claim 27, wherein the elongate member has a plurality of openings extending along its length. In a surgical instrument assembly,
A cannulated drill made of a biocompatible material and having a proximal end, a distal end, an inner surface, and an outer surface, the inner surface comprising an elongate member defining a lumen, wherein the lumen comprises the lumen. The cannula extending along the length of the elongated member, the distal end having at least one bone cutting edge, and the proximal end having a connector for matingly engaging a distal end of a syringe with the proximal end of the elongated member. With drill
A syringe having a housing defining a cavity, the housing having a proximal end and a distal end, the distal end of the syringe being mateably engageable with the proximal end of the elongate member. Wherein the lumen of the elongate member and the cavity of the housing are in fluid communication with each other when the distal end of the syringe is matably engaged with the proximal end of the elongate member. A surgical instrument assembly comprising: 35. The assembly of claim 34, further comprising a plunger having a plunger head, wherein the cavity of the housing is adapted to receive the plunger. 35. The assembly of claim 34, wherein said connector is a luer lock connector. 35. The assembly of claim 34, wherein the elongate member has a plurality of openings extending along a length of the elongate member. In a kit for treating pseudoarthritis,
A cannulated drill made of a biocompatible material and having a proximal end, a distal end, an inner surface, and an outer surface, the inner surface comprising an elongate member defining a lumen, wherein the lumen comprises the lumen. The cannula extending along the length of the elongated member, the distal end having at least one bone cutting edge, and the proximal end having a connector for matingly engaging a distal end of a syringe with the proximal end of the elongated member. With drill
A syringe having an elongated obturator sized to fit within the lumen of the drill and a housing defining a cavity, the housing having a proximal end and a distal end, the syringe having a distal end and a distal end. A distal end is matably engageable with the proximal end of the elongate member, and the lumen of the elongate member and the cavity of the housing are matable with the distal end of the syringe with the proximal end of the elongate member. A kit for treating pseudoarthritis, the kit comprising: