Drug eluting surgical screw

Abstract

The present invention is directed to a method of reducing the risk of infection following surgery utilizing the drug eluting surgical screw disclosed herein to secure an implant in an animal following surgery. The drug eluting screw includes a drug eluting component that can elute a therapeutic agent locally at the surface of the implant reducing the risk of infection.

Claims

1. A method of reducing risk of infection at a fracture fixation site comprising: implanting a fracture fixation implant at a site of a bone fracture, the fracture fixation implant defining a surface and including at least one aperture extending from the surface through the implant; applying a drug eluting screw through the at least one aperture and into the bone at the fracture site so as to secure the fracture fixation implant to the bone, wherein the drug eluting screw includes a drug eluting component comprising a carrier matrix including at least one antibiotic; and, eluting the at least one antibiotic from the carrier matrix at an elution rate of at least 50% by weight of the at least one antibiotic within a period of less than 7 days, wherein the at least one antibiotic elutes locally along the surface of the fracture fixation implant.

2. The method of claim 1, wherein the at least one antibiotic comprises at least two antibiotics such that there is at least a first antibiotic and a second antibiotic, and wherein the step of eluting comprises eluting the first antibiotic at a first elution rate and eluting the second antibiotic at a second elution rate.

3. The method of claim 2, wherein the first elution rate and the second elution rate are each at least 50% by weight of the first antibiotic and the second antibiotic respectively within a period of 7 days, and the first elution rate is different from the second elution rate.

4. The method of claim 2, wherein the drug eluting component comprises at least one layer, and wherein the first antibiotic and the second antibiotic are both contained in a same layer of the at least one layer.

5. The method of claim 2, wherein the drug eluting component comprises multiple layers, and wherein the first antibiotic is contained in a first layer of the multiple layers and the second antibiotic is contained in a second layer of the multiple layers.

6. The method of claim 2, wherein the drug eluting component comprises multiple layers, and wherein a first layer of the multiple layers is a barrier layer that contains no antibiotic, and a second layer of the multiple layers contains the first antibiotic and the second antibiotic, and further wherein the step of eluting comprises inhibited diffusion of the first and second antibiotics from the second layer through the first layer.

7. The method of claim 1, wherein the drug eluting component comprises multiple layers, and wherein a first layer of the multiple layers is a barrier layer that contains no antibiotic, and a second layer of the multiple layers contains the at least one antibiotic, and further wherein the step of eluting comprises inhibited diffusion of the at least one antibiotic from the second layer through the first layer.

8. The method of claim 1, wherein the carrier matrix defines a concentration gradient of the at least one antibiotic within the drug eluting component from a direction at a surface of the drug eluting component through a depth of the drug eluting component.

9. The method of claim 1, wherein the carrier matrix comprises a bioabsorbable polymer compounded with the at least one antibiotic.

10. The method of claim 9, wherein the carrier matrix further comprises a nonabsorbable polymer.

11. The method of claim 1, wherein the carrier matrix comprises a water swellable additive such that the step of eluting comprises swelling the drug eluting component with water.

12. The method of claim 1, wherein the carrier matrix comprises a soluble additive such that the step of eluting comprises dissolving the soluble additive.

13. The method of claim 1, wherein the carrier matrix comprises a soluble additive such that the step of eluting comprises generating pores in the carrier matrix.

14. The method of claim 13, wherein the carrier matrix further comprises a nonabsorbable polymer.

15. The method of claim 1, wherein the carrier matrix comprises an erodible ceramic material such the step of eluting comprises eroding the ceramic material.

16. The method of claim 1, wherein the drug eluting component is a film, and wherein the at least one antibiotic is compounded in the carrier matrix.

17. The method of claim 1, wherein the at least one antibiotic is dissolved within the carrier matrix.

18. The method of claim 1, wherein the at least one antibiotic is present as discrete particles in the carrier matrix.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The foregoing summary, as well as the following detailed description of embodiments of the present invention, will be better understood when read in conjunction with the appended drawings of exemplary embodiments. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown.

(2) In the drawings:

(3) FIG. 1A is a top view and FIG. 1B is a side perspective partial cross-sectional view of a surgical screw according to one embodiment;

(4) FIG. 2A is a top view and FIG. 2B is a side perspective partial cross-sectional view of an embodiment of a surgical screw having a drug eluting matrix in the drive recess;

(5) FIG. 3A is a top view and FIG. 3B is a side perspective partial cross-sectional view of an embodiment of a surgical screw having a drug eluting matrix in the drive recess with a diffusion barrier layer;

(6) FIG. 4A is a top view and FIG. 4B is a side perspective partial cross-sectional view of an embodiment of a surgical screw having two layers of drug eluting matrix in the drive recess, containing two different drugs;

(7) FIG. 5A is a top view and FIG. 5B is a side perspective partial cross-sectional view of an embodiment of a surgical screw having a drug eluting matrix in the drive recess with a graded drug concentration;

(8) FIG. 6A is a top view and FIG. 6B is a side perspective partial cross-sectional view of an embodiment of a surgical screw having an additional reservoir added to the bottom of the drive recess and having a drug eluting matrix in the drive recess;

(9) FIG. 7A is a top view and FIG. 7B is a side perspective partial cross-sectional view of an embodiment of a surgical screw having a lip configured and dimensioned to retain a drug eluting component when the drug eluting component is in a cured condition; and,

(10) FIG. 8 is a schematic side perspective cross-sectional view of a surgical screw securing a fracture fixation implant to bone according to an embodiment of the disclosure.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

(11) With reference to the accompanying drawings, various embodiments of the present invention are described more fully below. Some but not all embodiments of the present invention are shown. Indeed, various embodiments of the invention may be embodied in many different forms and should not be construed as limited to the embodiments expressly described. Like numbers refer to like elements throughout. The singular forms “a,” “an,” and “the” include the singular and plural unless the context clearly dictates otherwise.

(12) As shown generally in FIGS. 1A-7B, embodiments of the present invention are directed toward a surgical screw 100. In some embodiments, the surgical screw has a shaft 110. In one embodiment, the shaft 110 has a threaded portion 120. In certain embodiments, surgical screw 100 includes a head 140 disposed at a proximal end 130 of the shaft 110. In one embodiment, the head 140 has a drive recess 150. In one embodiment, the drive recess 150 is hexagonally shaped. Although illustrated as being hexagonally shaped, it is envisioned that the shape of the drive recess 150 may be configured in any manner suitable for distributing an insertion force throughout the screw, e.g., other polygonal or generally polygonal shapes, semi-circular, slotted, cross-recessed, torx star, or multiple round holes.

(13) Referring to FIG. 2B, the drive recess 150, in certain embodiments, has a reservoir region 160 and a driver engagement region 170. As seen by comparing FIGS. 2B and 6B, in certain embodiments, the reservoir region 160 can be of varied shape and depth. The reservoir region 160 can be any region of the head 140 of the screw 100 that can be coated with a drug eluting component 200 in a manner that will not substantially impair a connection between a driver and the surgical screw 100 when the driver is operably disposed within the driver engagement region 170. The driver engagement region 170 can be any region of the head 140 of the screw 100, either coated or uncoated with the drug eluting component 200, that is engageable with a driver when the driver is operably disposed within the head 140. The reservoir region 160 and driver engagement region 170 need not be exclusive and may overlap.

(14) In one embodiment, the reservoir region 160 defines a reservoir volume 210, the drive recess 150 defines a driver recess volume 220 and the reservoir volume 210 is from about 10% to about 12% of the driver recess volume. In other embodiments, the reservoir volume 210 is about 8%, about 8.5%, about 9%, about 9.5%, about 10%, about 10.5%, about 11%, about 11.5%, about 12%, about 12.5%, about 13%, about 13.5%, about 14% or any range determinable from the preceding percents (for example, about 8% to about 9.5% or about 8.5% to about 13%) of the driver recess volume 220.

(15) In certain embodiments, multiple layers of drug eluting components can be layered into the reservoir region 160 of the drive recess 150 to allow for multiple therapeutic agents to be released at different rates, sequentially, or simultaneously in different concentrations. One of the layers may not contain a therapeutic agent, but serve as a barrier layer to inhibit diffusion of the drug. Exemplary materials which could act as a barrier layer include bioabsorbable polymers such as polycaprolactone or polyglycolide, natural fatty acids such as palmitic acid or stearic acid, and natural biopolymers such as collagen or alginate.

(16) As shown in FIG. 3B, in one embodiment, both a diffusion barrier layer 300 and a drug eluting component 200 are disposed within the reservoir region 160 of the drive recess 150.

(17) Further, FIG. 4B illustrates an exemplary view of the surgical screw where two drug eluting components, drug eluting component 200 and drug eluting component 400, are disposed within the reservoir region 160 of the drive recess 150. In some embodiments, drug eluting component 200 and drug eluting component 400 include different therapeutic agents. In other embodiments, the drug eluting component 200 and drug eluting component 400 are configured to elute a therapeutic agent at differing release rates.

(18) FIG. 5B shows an exemplary embodiment of the invention having a drug eluting component with a graded concentration 500, e.g., a therapeutic agent being less concentrated at the surface and gradually more concentrated at deeper depths or, alternatively, a therapeutic agent being more concentrated at the surface and gradually less concentrated at deeper depths.

(19) As shown generally in FIG. 2B, one embodiment of the present invention includes a drug eluting component 200 disposed within the reservoir region 160 of the drive recess 150. In certain embodiments, the drug eluting component 200 is positioned in a manner so that it does not substantially impair a connection between a driver and the surgical screw 100 when the driver is operably disposed within the driver engagement region 170. For example, as shown in FIG. 2B, the drug eluting component 200 may be positioned at the base 230 of the head 140. In other embodiments, the reservoir region 160 of the drive recess 150 is adjacent to the driver engagement region 170 and the drug eluting component 200 does not extend into the driver engagement region 170.

(20) In one embodiment, the reservoir region 160 is shaped and dimensioned to retain the drug eluting component 200 when the drug eluting component 200 is in a cured condition. For example, as shown in FIGS. 7A and 7B, the surgical screw 100 includes a lip 700 configured and dimensioned to retain the drug eluting component 200 when the drug eluting component 200 is in a cured condition.

(21) In one embodiment, the drug eluting component 200 includes a carrier matrix containing a therapeutic agent. In certain embodiments, the carrier matrix includes a material that facilitates the release rate of the therapeutic agent into the body, e.g., a polymer, ceramic, or hydrogel. In one embodiment, the carrier matrix includes a bioabsorbable polymer, e.g., polycaprolactone, polylactic acid, polyglycolic acid, polyethylene glycol, or a combination thereof.

(22) In other embodiments, the carrier matrix includes a soluble additive which dissolves at a controlled rate, generating pores through which the therapeutic agent can elute. Examples of a soluble additive would include polyethylene glycol, polyvinyl alcohol, glycerine, salts or water soluble crystalline solids. By varying the amount of soluble additive, the elution rate of the therapeutic agent may be modified. Certain embodiments having differing release rates, can be achieved by having multiple drug eluting components, each having differing bioabsorbable matrices having differing soluble additives.

(23) In another embodiment, the carrier matrix includes a hydrophobic bioabsorbable polymer that contains a water swellable additive that swells with water after implantation into the body, allowing the therapeutic agent to be released at an increased rate. By varying the amount of water swellable additive, the elution rate of the therapeutic agent may be modified.

(24) In one embodiment, the carrier matrix includes a nonabsorbable polymer, e.g., poly(methyl methacrylate).

(25) In another embodiment, the carrier matrix includes a nonabsorbable polymer and a soluble additive, e.g., polyethylene glycol, polyvinyl alcohol, glycerine, salts or water soluble crystalline solids. The soluble additive dissolves at a controlled rate, generating pores in the nonabsorbable matrix through which a therapeutic agent can elute.

(26) In certain embodiments, the carrier matrix includes a blend of bioabsorbable polymer and nonabsorbable polymer.

(27) In other embodiments, the carrier matrix includes an erodible or biostable ceramic, e.g., silica, hydroxyapatite, calcium phosphate, bioglass, or a combination thereof.

(28) In one embodiment, the carrier matrix includes a natural biopolymer, e.g., gelatin, alginates, chitosan, collagen or hyaluronate.

(29) In one embodiment, the therapeutic agent includes an antibiotic or a combination of multiple antibiotics. In one embodiment, the therapeutic agent includes gentamicin.

(30) In other embodiments, the therapeutic agent includes steroids, anti-inflammatory drugs, anti-proliferative compounds, antimycotic compounds, an antimitotic compounds, antimetabolite compounds, pain-relieving drugs, corticosteroids, angiostatic steroids, non-steroidal anti-inflammatory agents, and/or co-drugs.

(31) In certain embodiments, the therapeutic agent includes a growth factor, e.g., bone morphogenetic protein 2 (BMP-2). In other embodiments, the therapeutic agent includes a local anesthetic, e.g., lidocaine.

(32) The therapeutic agent, in certain embodiments, can either be dissolved completely into the material that facilitates its release into the body or remain as discrete particles within that material.

(33) In one embodiment, the therapeutic agent constitutes at least about 20 wt % of the drug eluting component prior to any implantation of the drug eluting surgical screw 100. In one embodiment, the therapeutic agent constitutes between about 20 wt % and about 60 wt % of the drug eluting component prior to any implantation of the drug eluting surgical screw 100. In one embodiment, the therapeutic agent constitutes between about 20 wt % and about 40 wt % of the drug eluting component prior to any implantation of the drug eluting surgical screw 100. In other embodiments, the therapeutic agent constitutes about 20 wt %, about 21 wt %, about 22 wt %, about 23 wt %, about 24 wt %, about 25 wt %, about 26 wt %, about 27 wt %, about 28 wt %, about 29 wt %, about 30 wt %, about 31 wt %, about 32 wt %, about 33 wt %, about 34 wt %, about 35 wt %, about 36 wt %, about 37 wt %, about 38 wt %, about 39 wt %, about 40 wt %, about 41 wt %, about 42 wt %, about 43 wt %, about 44 wt %, about 45 wt %, about 46 wt %, about 47 wt %, about 48 wt %, about 49 wt %, about 50 wt %, about 51 wt %, about 52 wt %, about 53 wt %, about 54 wt %, about 55 wt %, about 56 wt %, about 57 wt %, about 58 wt %, about 59 wt %, about 60 wt % or any range determinable from the preceding weight percents (for example, about 51 wt % to about 55 wt % or about 30 wt % to about 52 wt %) of the drug eluting component prior to any implantation of the drug eluting surgical screw 100.

(34) In one embodiment, the drug eluting component 200 is configured to elute at least about 80% of the therapeutic agent over a three day period starting from when the drug eluting surgical screw 100 is implanted into the animal. In other embodiments, the drug eluting component 200 is configured to elute about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100% or any range determinable from the preceding percents (for example, about 50% to about 77% or about 85% to about 94%) of the therapeutic agent over a one day, two day, three day, four day, five day, six day, seven day or any range determinable from the preceding days (for example, 1-3 days or 3-4 days) period starting from when the drug eluting surgical screw 100 is implanted into the animal.

(35) In one embodiment, the present invention includes a method of manufacturing a drug eluting surgical screw 100. In one embodiment, the method includes forming a film derived from a drug eluting component. In one embodiment, a film is formed by mixing a drug eluting component with a solvent to form a solution and heating the solution to evaporate the solvent and form a film. In another embodiment, a film is formed by subjecting a drug eluting component to a melting process, e.g., by a process including compounding, and then subjecting the melted drug eluting component to extrusion or compression molding. In one embodiment, after the film has been formed, the method includes, configuring at least a portion of the film to a size and shape that complements a drive recess of a surgical screw. In one embodiment, the method further includes placing the at least a portion of the film into the drive recess 150 of the surgical screw 100. In one embodiment, after placing the at least a portion of the film into the drive recess 150, heating the at least a portion of the film to conform to the size and shape of a cross-section of the drive recess. In one embodiment, after heating the at least a portion of the film, the method includes, pressing the at least a portion of the heated film into the drive recess 150. In one embodiment, a forming tool, e.g., a screwdriver with an end shaped to fit within the drive recess, is used, e.g., used by pressing the heated film into the drive recess 150, to form a sufficient bond between the at least a portion of the heated film and the drive recess side walls.

(36) In one embodiment, the method of manufacturing a drug eluting surgical screw 100 described above is repeated to create a drug eluting surgical screw 100 having multiple layers of drug eluting components, e.g., as shown in FIGS. 4A and 4B.

(37) Referring to FIG. 8, in one embodiment (shown schematically), the present invention includes a method of using the drug eluting surgical screw 100 to secure an implant 11, e.g., a fixation plate. In one embodiment, the method includes forming a cavity 65 in a bone 55 for receiving the drug eluting screw 100, e.g., via drilling. The method further may include placing an implant 11 having an aperture 21 against the bone 55, the aperture 21 being aligned with the cavity 65. The method further may include using a driver to fix the drug eluting screw 100 to the bone 55, whereby the implant 11 is held between the bone 55 and the head 140 of the screw.

(38) Still referring to FIG. 8, in one embodiment the present invention includes a method of reducing the risk of infection following surgery. In one embodiment, the method includes using the drug eluting surgical screw 100 to secure an implant 11 in an animal following surgery. In certain embodiments, the drug eluting component 200 will elute an antibiotic, e.g., gentamicin, locally at the surface of the implant 11 thereby reducing the risk of infection.

(39) It will be appreciated by those skilled in the art that changes could be made to the exemplary embodiments shown and described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the exemplary embodiments shown and described, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the claims. For example, specific features of the exemplary embodiments may or may not be part of the claimed invention and features of the disclosed embodiments may be combined.

(40) It is to be understood that at least some of the figures and descriptions of the invention have been simplified to focus on elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that those of ordinary skill in the art will appreciate may also comprise a portion of the invention. However, because such elements are well known in the art, and because they do not necessarily facilitate a better understanding of the invention, a description of such elements is not provided herein.

(41) Further, to the extent that the method does not rely on the particular order of steps set forth herein, the particular order of the steps should not be construed as limitation on the claims. The claims directed to the method of the present invention should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the steps may be varied and still remain within the spirit and scope of the present invention.