Patent Publication Number: US-2023158281-A1

Title: Systems, devices, and methods for delivering a substance within a target tissue

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims priority to co-pending U.S. Provisional Application Ser. No. 63/007,995, filed Apr. 10, 2020, which is hereby incorporated by reference herein in its entirety. 
    
    
     BACKGROUND 
     There are a variety of health conditions that are treated using invasive surgical procedures. One such condition is nasal inflammatory disease, which can result from allergies. Nasal inflammatory disease can take the form of the growth of polyps within the nasal cavity as well as turbinate hypertrophy. In either case, the nasal passages are constricted and it becomes more difficult for the individual to breathe through his or her nose. 
     In most situations, initial treatment of nasal polyps and turbinate hypertrophy involves the application of topical corticosteroids to the affected area as well as administration of oral corticosteroids. While such steroids can be highly effective in shrinking polyps and the turbinates, invasive surgery is often required as topical and oral corticosteroid delivery often are insufficient to control the growth of nasal polyps and the swelling of the turbinates. This is unfortunate as, whether the surgery is to remove the polyps or reduce the size of the turbinates, such procedures often must be performed in an operating room under anesthesia. This increases both the costs and the risks of treatment. In addition, the relief such procedures provide is often temporary as it is common for removed nasal polyps to return and, as turbinate reduction does not address the underlying inflammatory pathology, for the turbinates to again expand and constrict the nasal passages. Because of this, it is not unusual for an individual who has had nasal surgery to need the surgery to be performed repeatedly on a periodic basis. 
     Given the disadvantages associated with surgical treatments, not only in relation to nasal inflammatory disease but also other conditions in which surgery is an option, it can be appreciated that it would be desirable to have alternative treatment options. For example, it would be desirable to be able to deliver a substance, such as a drug, within a target tissue in a manner that is efficacious enough to obviate the need for surgery, or at least delay the need for the surgery and/or reduce the frequency with which the surgery must be performed. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present disclosure may be better understood with reference to the following figures. Matching reference numerals designate corresponding parts throughout the figures, which are not necessarily drawn to scale. 
         FIG.  1 A  is a first perspective view of an embodiment of an implant. 
         FIG.  1 B  is a second perspective view of the implant of  FIG.  1 A . 
         FIG.  1 C  is a side view of the implant of  FIG.  1 A . 
         FIG.  2    is a perspective view of an embodiment of an implantation device that is configured to implant the implant of  FIG.  1    into a target tissue. 
         FIG.  3    is a side view of multiple implants of the type shown in  FIG.  1    arranged in series as they would be inside of a barrel of the implanting device of  FIG.  2   . 
         FIG.  4    is a schematic view illustrating implantation of an implant within a nasal polyp of an individual. 
         FIG.  5 A  is a first perspective view of another embodiment of an implant. 
         FIG.  5 B  is a second perspective view of the implant of  FIG.  5 A . 
         FIG.  5 C  is a side view of the implant of  FIG.  5 A . 
         FIG.  6    is a perspective view of an embodiment of an implantation device that is configured to implant the implant of  FIG.  5    into a target tissue. 
         FIG.  7    is a detail perspective view of a distal tip of the implantation device of  FIG.  6    shown loaded with the implant of  FIG.  5   . 
     
    
    
     DETAILED DESCRIPTION 
     As described above, it would be desirable to be able to deliver a substance within a target tissue in a manner that is efficacious enough to obviate the need for surgery, or at least delay the need for the surgery and/or reduce the frequency with which the surgery must be performed. Disclosed herein are systems, devices, and methods that enable such delivery. In some embodiments, a small sharp-tipped implant is configured for implantation within a target (e.g., diseased) tissue. The implant comprises one or more substances, such as one or more drugs, that are to be delivered to the tissue over a period of time. As the implant is provided with a sharp tip, it can pierce tissue and, therefore, can be implanted by simply driving it into the tissue, thereby obviating the need for a needle, trocar, or other sharp delivery device. In some embodiments, the one or more substances are released by the implant over an extended period of time, such as several weeks or months, which can be more efficacious than repeated topical application or injection of such substances. In some embodiments, the implant comprises one or more anchoring elements that prevent the implant from migrating or dislodging. In some embodiments, the implant is bioabsorbable so that there is no need to remove the implant. 
     In the following disclosure, various specific embodiments are described. It is to be understood that those embodiments are example implementations of the disclosed inventions and that alternative embodiments are possible. Such alternative embodiments include hybrid embodiments that include features from different disclosed embodiments. All such embodiments are intended to fall within the scope of this disclosure. 
       FIGS.  1 A- 1 C  illustrate an embodiment of an implant  10  that is configured to deliver a substance within a target tissue in which it is implanted. In some embodiments, the implant  10  is specifically sized and configured for implantation into a nasal polyp or the nasal mucosa from which the polyp extends. Notably, however, that application is only an example as the implant  10 , or others similar to it, could be configured for implantation into other tissues of the body. 
     As is shown in  FIGS.  1 A- 1 C , the implant  10  generally comprises an elongated body  12 . Although the body  12  is illustrated as being generally cylindrical in the figures, it is noted that other shapes are possible as the shape of the body is not critical to its functionality. The body  12  includes a distal (front) end  14  and a proximal (rear) end  16 . The distal end  14  forms a sharp, pointed tip  18  that is configured to pierce and cut through target tissue. As is illustrated in the figures, the tip  18  can be generally conical, although any shape that enables the implant  10  to pierce and cut through tissue can be used. When tip  18  comprises a right circular cone, the spread angle of the cone can range from approximately 50 to 70 degrees. As is apparent from  FIGS.  1 B and  1 C , the proximal end  16  of the body includes a cavity  20  that has a size and shape that is specifically configured to receive the pointed tip  18  to enable multiple implants  10  to nest with each other end-to-end, as described below in relation to  FIGS.  2  and  3   . In this example, in which the pointed tip  18  is generally conical, the cavity  20  defines a generally conical space that the pointed tip of another implant  10  can occupy such that the surfaces of the pointed tip contact the surfaces of the cavity. 
     Although the size of the implant  10  can depend upon the particular application in which the implant is going to be used, the implant is, in many embodiments, very small. For example, when the implant  10  is configured for implantation into nasal polyps, the body  12  can be approximately 3 to 10 mm (e.g., 6 mm) long and have a cross-sectional dimension (e.g., diameter) of approximately 0.5 to 2 mm (e.g., 1.5 mm). 
     In some embodiments, the body  12  can be a solid member that is impregnated with one or more substances that are to be delivered to the target tissue. In other embodiments, such as that shown in  FIG.  1 C , the body  12  can comprise an internal compartment  22  in which the one or more substances can be contained. In the illustrated embodiment, the compartment  22  is also generally elongated and cylindrical just like the body  12 . Although only a single continuous compartment  22  is shown in  FIG.  1 C , it is noted that, in other embodiments, the compartment can be divided into multiple sub-compartments and/or the body  12  can comprise multiple compartments. 
     When the body  12  includes one or more internal compartments, such as compartment  22 , the body can further comprise one or more apertures  24  that extend through the body to the compartment(s) to enable the one or more substances contained therein to be slowly released into the surrounding tissue. In the illustrated embodiment, the implant  10  comprises a single aperture  24  that is configured as a narrow, elongated slit that extends along the length of the internal compartment  22 . While a slit is illustrated in the figures, it is noted that the aperture  24  can have other shapes. For example, the body  12  can be provided with one or more circular apertures that extend to the internal compartment  22 . Notably, the number, size, and shape of the apertures can be selected to control the rate at which the one or more substances contained within the body  12  are released into the surrounding tissue. When there are multiple compartments or sub-compartments, each can have one or more associated apertures, which can be of different sizes and shapes to individually control the release rate of each substance contained in each compartment/sub-compartment. 
     Regardless of whether or not the body  12  includes an internal compartment, the body can be made of a biocompatible, bioabsorbable material, such as polyglycolic acid (PGA), polylactic acid (PLA), poly lactic-co-glycolic acid (PLGA), polydimethylsiloxane (PDMS), poly(L-lactide) (PLLA), and Poly-L/D-lactide (PLDLA). In such a case, there is no need to remove the implant  10  after it no longer can deliver any further substance to the tissue. In some embodiments, the material can include proteolytic/fibrolytic enzymes to prevent capsule formation around implant  10 . It is noted that, when the body  12  is made of a bioabsorbable material, one or more of the dimensions of the body can be selected to control the timing of the release of the one or more substances. For example, when the body  12  includes the internal compartment  22 , the thickness of the walls can be selected to control how long it takes for them to dissolve to the point at which they no longer contain the one or more substances. In cases in which there are multiple compartments and/or sub-compartments that contain different substances, the thicknesses of the walls can be varied in relation to their associated compartments/sub-compartments to individually control the rates of release of the different substances. 
     A wide variety of substances can be delivered with the implant  10 , whether the substances are impregnated into the material of the body  12  or contained within the internal compartment  22  of the body. Examples of such substances include corticosteroids, antihistamines, antimicrobials, chemotherapeutics, biologic agents, monoclonal antibodies, botulinum toxin, desiccating agents, leukotriene receptor modulations, radioactive substances for brachytherapy, antigens for immunotherapy and desensitization, vasoconstrictors, vasodilators and interleukin modifiers. It is also noted that the implant  10  can be coated with one or more substances as well. 
     With further reference to  FIGS.  1 A- 1 C , the implant  10  includes one or more anchoring elements  26  that are configured to prevent migration or dislodging of the implant after it has been implanted. The anchoring elements  26  can be unitarily formed with the body  12  and, therefore, made of the same material as the body. As is apparent from the figures, the anchoring elements  26  extend radially outward from body  12  and are equally spaced from each other about the circumference of the body. In the illustrated embodiment, the implant  10  comprises three such anchoring elements  26 , each positioned near the distal end  14  of the body  12 . More particularly, the distal-most portions of the anchoring elements  26  are positioned immediately proximal of the pointed tip  18  at the distal end  14  of the body  12 . 
     In some embodiments, each anchoring element  26  is configured as a swept-back, pointed barb having a sharp tip  30  that faces away from the tip  18  of the body  12  toward the proximal end  16  of the body. In some embodiments, each barb  26  can have a length that is approximately 10 to 20 percent of the total length of the implant  10 , a height (in the radially outward direction normal to the surface of the body  12 ) that is approximately 10 to 20 percent of the length of the barb, and a width that is approximately 15 to 25 percent of the length of the barb. 
     As is most clearly illustrated in  FIG.  1 C , each barb  26  of the illustrated embodiment generally forms a parallelogram shape when viewed from the side given that the top and bottom edges of the barb are parallel with each other (and the surface of the body  12 ) and the distal (front) edge and the proximal (rear) edge of the barb are also parallel with each other (and form an acute angle with the surface of the body). Notably, the angle formed between the distal edge and the bottom edge of the barb  26 , as well as the angle formed between the proximal edge of the barb and the surface of the body  12 , is a small angle that, for example, can range from approximately 10 to 20 degrees. At the distal (front) edge of the barb  26 , this small angle facilitates passage of the implant  10  through tissue during implantation. At the proximal (rear) edge of the barb  26 , the small angle, in combination with the relatively small height of the barb (again when viewed from the side as in  FIG.  1 C ) can result in the proximal portion of the barb that forms the sharp tip  30  being flexible. In some embodiments, the proximal portion of the barb  26  is compressed inward toward the body  12  during implantation and then extends back outward into the orientation shown in  FIG.  1 C  after the implant  10  has been implanted so that the implant is less likely to migrate backward and possibly dislodge. 
       FIG.  2    illustrates an embodiment of an implantation device  40  that is configured to implant implants, such as that shown in  FIG.  1   , into target tissue. As shown in  FIG.  2   , the implantation device  40  is designed as a hand-held device that includes a body  42 , a grip  44  that extends downward from the body, an actuation mechanism that includes a trigger  46  associated with the grip, a coupling element  48  that extends forward from the body, and a delivery rod  50  that extends into the body from a rear of the body. Shown inserted into the coupling element  48  is a removable and replaceable barrel  52  having an inner lumen that is preloaded with multiple (e.g., 5-10) implants  10 . The implants  10  are linearly aligned and nested with each other (in the manner illustrated in  FIG.  3   ) within the barrel lumen. That is, the pointed tip  18  of each trailing implant  10  is received within the cavity  20  of the preceding implant  10 , as depicted in  FIG.  3   . When the implants  10  are aligned in this manner, the forces associated with implantation are evenly distributed within the bodies  12  of the implants such that the walls of the implants (when the implants are provided with internal cavities  22 ) can be made thinner without risking the integrity of the bodies. 
     In some embodiments, the barrel  52  can comprise internal channels that are formed in the walls of its inner lumen and configured to receive the barbs  26  of the implants  10 . In such cases, the inner lumen of the barrel  52  has an inner transverse dimension (e.g., diameter) that is only slightly larger than the outer transverse dimension (e.g., diameter) of the bodies  12  of the implants  10 . In some embodiments, the barrel  52  is flexible to facilitate positioning of the tip of the barrel and, therefore, the location at which the next implant  10  can be implanted. 
       FIG.  4    illustrates an example of implantation of an implant  10  using the implantation device  40 . As is apparent from this figure, implants  10  are being implanted within nasal polyps  60  (i.e., intra-polyp implantation) within the nasal cavity  62  of an individual (e.g., patient)  64 . To achieve such implantation, the barrel  52  of the implantation device  40  is inserted through one of the patient&#39;s nostrils  66  and the distal tip of the barrel is positioned so as to contact a given polyp  60 . While  FIG.  4    illustrates an example of implantation of an implant  10  within a polyp  60 , it is noted that the implant alternatively can be implanted in the nasal mucosa that surrounds the polyp. 
     Once the tip of the barrel  52  is in position, the actuation mechanism of the implantation device  40  can be activated by an operator (e.g., physician) by pulling the trigger  46  to eject a single implant  10 . In some embodiments, ejection of more than one implant  10  is prevented with appropriate means contained within the implantation device  40 , such as an indexing mechanism. When the implant  10  is ejected, it is forced into the polyp  60 . Specifically, the pointed tip  18  of the implant  10  pierces the polyp  60  so that the implant can lodge within the polyp and the barbs  26  ensure that the implant does not migrate from the position in which it has been implanted. As noted above, inward flexing of the barbs  26  during implantation and the return of the barbs to their original orientations once implantation has been achieved may occur, which prevents the implant from backing out. Further implants  10  can then be implanted into the other polyps  60  and/or surrounding mucosa as desired. Once each implant  10  or each needed implant  10 , has been implanted, the barrel  52  can be removed and discarded. A new, preloaded barrel  52  can then be inserted into the coupling element  48  so that the implantation device  40  can be used on the next patient. 
     Once implanted, the implants  10  release the one or more substances they comprise into the target tissue. As the implant  10  is made of a bioabsorbable material, the implant slowly dissolves within the tissue. In some embodiments, the implant  10  can deliver one or more substances to the tissue for approximately 30 to 90 days, after which time the implant will have been completely dissolved. 
     Although an implantation device  40  has been disclosed that can be used to implant the implants  10 , it is noted that it is possible to implant each implant without using the implantation device. For example, the implants  10  can be implanted using an endoscope. In another example, the implants  10  can be implanted by hand using an appropriate device, such as forceps. 
       FIGS.  5 A- 5 C  illustrate another embodiment of an implant  70  that is configured to deliver a substance within a target tissue. In some embodiments, the implant  70  is specifically sized and configured for implantation into the nasal turbinates. As is shown in the figures, the implant  70  is similar in many ways to the implant  10 . Accordingly, the implant  70  generally comprises an elongated body  72  that includes a distal (front) end  74  and a proximal (rear) end  76 . The distal end  74  forms a sharp, pointed tip  78  that is configured to pierce and cut through target tissue. As with the tip  18  of the implant  10 , the tip  78  can be generally conical. In embodiments in which the tip  78  comprises a right circular cone, the spread angle of the cone can range from approximately 20 to 40 degrees. For the turbinate application, the body  72  can be approximately 5 to 40 mm long and have a cross-sectional dimension (e.g., diameter) of approximately 0.5 to 10 mm. 
     The body  72  can be a solid member that is impregnated with one or more substances that are to be delivered to the target tissue. Alternatively, as shown in  FIG.  5 C , the body  72  can comprise an internal compartment  82  (or multiple compartments and/or sub-compartments) in which the one or more substances can be contained. When the body  72  includes one or more internal compartments, such as compartment  82 , the body can further comprise one or more apertures  84  that extend through the body to the compartments to enable the one or more substances contained therein to be slowly released into the surrounding tissue. As before, the implant  70  comprises a single aperture  84  that is configured as a narrow, elongated slit, although the number, size, and shape of the apertures can be selected to control the rate at which the one or more substances contained within the body  72  are released into the surrounding tissue. 
     Regardless of whether or not the body  72  includes an internal compartment, it can be made of a biocompatible, bioabsorbable material, such as one of the materials identified above for the construction of the implant  10 . As above, a wide variety of substances can be delivered with the implant  70 , whether they are impregnated into the material of the body  72  or contained within the internal compartment  82  of the body. 
     While the above-described aspects of the implant  70  are similar to those of the implant  10 , the implant  70  differs in some respects. First, instead of having multiple anchoring elements, the implant  70  is provided with a single anchoring element  86 . The anchoring element  86  is positioned near the distal end  74  of the body  72 . More particularly, the distal-most portion of the anchoring element  86  is positioned immediately proximal of the pointed tip  78  at the distal end  74  of the body  72 . 
     In some embodiments, the anchoring element  86  is configured as thin fin that resembles the tail fin of a fish or an airplane. In some embodiments, the fin  86  can have a length that is approximately 5 to 10 percent of the total length of the implant  10 , a height (in the radially outward direction normal to the surface of the body  72 ) that is approximately 40 to 60 percent of the length of the barb, and a width that is approximately 3 to 10 percent of the height of the barb. In such a case and assuming the dimensions identified above for the barbs  26 , the fin  86  is both taller and thinner than the barbs of the implant  10  on a relative basis. 
     As is most clearly illustrated in  FIG.  5 C , the fin  86  can also have the general shape of a parallelogram when viewed from the side given that the top edge and the bottom edge of the fin are parallel with each other (and the surface of the body  72 ) and the distal (front) edge and proximal (rear) edge of the fin are parallel with each other (and form an acute angle with the surface of the body). In the case of the fin  86 , however, the distal and top edges of the fin form a rounded corner that facilitates insertion of the implant  70  into target tissue. 
     With reference to  FIGS.  5 A- 5 C , the implant  70  further includes a retrieval tab  88  that extends proximally from the proximal end  76  of the body  72 . This tab  88  enables the implant  70  to be manually removed with forceps or another surgical device, if desired. 
       FIG.  6    illustrates an embodiment of an implantation device  90  that is configured to implant implants, such as that shown in  FIG.  5   . As shown in  FIG.  6   , the implantation device  90  can have the same configuration of the device  40  shown in  FIG.  2   . In fact, in some embodiments, the device  90  can be the same device as the device  40 . In such an embodiment, a single implantation device  40 ,  90  can be used to implant the implants  10  as well as the implants  70 . Referring to  FIG.  6   , the implantation device  90  can be a hand-held device that includes a body  92 , a grip  94 , a trigger  96 , a coupling element  98 , and a delivery rod  100 . Inserted into the coupling element  98  is a removable and replaceable barrel  102  that is specifically configured for use with the implant  70 . In cases in which a single implantation device  40 ,  90  is used for both implants  10  and implants  70 , the device is configured to alternately receive both barrels  52  and  102 . In other words, the barrels  52 ,  102  are interchangeable with the implantation device  40 ,  90 . In such cases, an implantation device  40 ,  90  can be part of an implantation system or kit that further includes a first barrel  52  that is preloaded with multiple implants  10  and a second barrel  102  that is preloaded with one or more implants  70 . Referring next to the detail view of  FIG.  7   , a single implant  70  can be received withing the distal tip of the barrel  102 , which includes a slot  104  that is configured to receive the anchoring element  86 . In other embodiments, the slot  104  can be longer, in which case the barrel  102  can receive two or more implants  70 . 
     In the case of turbinate implantation, the barrel  102  of the implantation device  90  is inserted through one of the patient&#39;s nostrils and the exposed tip  78  of the implant  70  is placed in contact with a turbinate. The trigger  96  of the implantation device  90  can then be pulled by the operator (e.g., physician) to eject the implant  70  into the turbinate. The operator can then rotate the implantation device about the longitudinal axis of the barrel  102  through approximately 90 degrees to fix the implant  70  in place, at which time the barrel can be withdrawn. 
     As noted above, the disclosed implants and implantation devices can be used in a variety of applications beyond nasal applications. In fact, the implants can be implanted into any soft tissue, cartilage, or bone, as well as polyps, cysts, and tumors, and can be used to deliver substantially any substance to the tissue in which they are implanted. Furthermore, it is noted that the implants can not only be used to deliver substances, they can, in addition or exception, be used to implant devices within a target tissue. Such devices could include electronic devices such as monitoring devices, tracking devices, and even micro- or nanorobotics. In such applications, the implants can be used to implant the electronic devices and the implants can then dissolve, leaving the electronic devices in place within the tissue.