HK1170650B

HK1170650B - Devices for treating pain associated with tonsillectomies

Info

Publication number: HK1170650B
Application number: HK12111606.9A
Authority: HK
Inventors: Jerome E. Hester; Anthony J. Abbate; Richard E. Kaufman; David C. Gale; Gail M. Zaler; Bin Huang; Lisa Earnhardt; Vijaykumar Rajasekhar
Original assignee: Intersect Ent, Inc.
Priority date: 2009-04-27
Filing date: 2010-04-27
Publication date: 2015-08-14

Description

Devices for treating pain associated with tonsillectomy

Cross Reference to Related Applications

The present application claims priority to U.S. provisional patent application No. 61/173,093 entitled "apparatus and method for treating pain associated with tonsillectomy," filed on even 4-27 of 2009, which is incorporated herein by reference in its entirety.

Technical Field

The present application relates generally to devices and methods for treating one or more tonsils, adenoids, and/or peripheral tissues.

Background

One of the oldest known surgical procedures, tonsillectomy, is a procedure during which one or more portions of the palatine tonsils ("tonsils") are removed. Adenoidectomies are procedures during the removal of one or more portions of the pharyngeal tonsils ("adenoids"). Tonsillectomies and adenoidectomies are frequently performed to alleviate one or more symptoms that may be associated with an infected or enlarged tonsils or adenoids, such as chronic pharyngolaryngitis, recurrent septic pharyngolaryngitis, abscesses, upper airway obstruction, ear infections, halitosis, and sleep apnea. Tissue can be removed by one of a number of methods, such as cryoablation, electrocautery ablation, laser ablation, Coblation (controlled ablation plasma technology), micro-debridement (microdebriding), radiofrequency ablation, and ultrasonic knife ablation (common surgical resection).

Tonsillectomies and adenoidectomies are very common, with over 800,000 cases being performed annually in the united states. Despite the frequent performance of these procedures and the various methods used for these procedures, tonsillectomies and adenoidectomies are still associated with substantial post-operative pain and discomfort. More particularly, there is typically a 7-10 day recovery period during which the patient may experience pain, discomfort, dehydration and weight loss. In addition, there is a post-operative bleeding rate of about 1-7%, as well as the risk of infection.

There has been little success in reducing pain or discomfort following tonsillectomies and adenoidectomies. Typically, the physician will prescribe antibiotics and narcotics (e.g., paracetamol, codeine) for post-operative pain. Oral administration of these antibiotics and anesthetics may be undesirable because swallowing can be extremely painful for the patient. Furthermore, the amount of narcotic ingested may lead to other undesirable side effects such as drowsiness, dizziness, light headedness, or complications arising from the exposure of the entire body to the effects of narcotics. Other post-operative treatment methods, including topical, intravenous, intra-wound and oral administration of anesthetics, non-steroidal anti-inflammatory drugs (NSAIDS), steroids and/or local anesthetics, have little effect on reducing pain or discomfort. Accordingly, it would be desirable to provide more effective methods of reducing pain or discomfort following tonsillar procedures (e.g., tonsillectomies, adenoidectomies, etc.).

Summary of The Invention

Described herein are devices and methods for treating tonsils, adenoids, and/or peripheral tissues. Typically, one or more devices are attached to or implanted in or around tissue and may be caused to release one or more drugs to the tonsils or adenoids. In certain aspects, the device is used to treat inflamed or enlarged tonsils or adenoids. In other versions, the device is used to assist post-operative recovery following a tonsillectomy or adenoidectomy (e.g., by local delivery of one or more drugs, by covering or treating exposed tissue, etc.).

In certain aspects, one or more sutures or suture-like materials may be at least partially implanted into tonsil tissue. In certain such regimens, one or more sutures are allowed to release one or more drugs to the tonsils. In other versions, the suture itself is anchored in the tissue (e.g., the suture may contain one or more unidirectional elements that pull the suture into the tissue in an initial direction, but not move in reverse). In other embodiments, the suture is biodegradable.

In other arrangements, one or more tissue-piercing devices may be implanted in, around, or near tonsillar tissue. Tissue piercing devices are typically designed to pierce, perforate, or penetrate tissue. In certain such versions, the tissue-piercing device comprises one or more wires, staples, or staples. In some versions, the tissue-piercing device is prevented from being removed from the tissue. In some such versions, the means for piercing tissue comprises one or more barbs, prongs, notches, threads, or combinations thereof.

In other arrangements, one or more clips may be attached to the tonsillar tissue. Typically the clip may comprise a surface member and one or more anchoring members. In some such arrangements, the surface member and the anchoring member may be made of a single material. In other aspects, one or more sutures or tissue-piercing devices may be used to attach the surface member to the tissue.

In other versions, one or more tissue constraint devices may be applied to the tonsillar tissue. In some such approaches, the tissue constraint device may stretch the tissue region. In other aspects, the tissue restraining device may assist in preventing movement of one or more tissues. The tissue constraint device may comprise a body member and may additionally comprise one or more anchors. The anchor may be used to attach the tissue restraining device to tissue and may have any suitable configuration of elements, as described in more detail below.

In some versions, multiple space-filling implants may be used to fill one or more spaces within tonsillar tissue. The space-filling implant may comprise one or more beads, tablets, beads (seeds), capsules, or combinations thereof. The space-filling implant may assemble itself to conform to the shape of one or more spaces in the tonsil tissue. In some aspects, one or more space-filling implants may be designed to rupture upon application of one or more forces or stimuli thereto.

Drawings

FIGS. 1A-1C are illustrations of tonsils, adenoids, and their peripheral anatomy.

Fig. 2A-2K depict exemplary versions of a device for piercing tissue.

Fig. 3 depicts a version of a filament containing a notch.

Fig. 4A-4D show exemplary versions of a tissue-piercing device anchored in tissue.

FIG. 5 depicts a version of a tissue piercing device containing staples.

Fig. 6A, 6B, 7A, 7B and 8 illustrate different versions of the device described herein, wherein the device comprises a staple.

Fig. 9A and 9B illustrate a perspective view and a side view, respectively, of one version of a device comprising a clip.

Fig. 10A, 10B, 11A, 11B and 12 are exemplary illustrations of versions of the device that include clips.

Fig. 13A-13D, 14, 15, 16A, 16B, 17, 18A and 18B are exemplary illustrations of versions of an apparatus for stretching or constraining tissue.

Fig. 19A, 19B and 20 are exemplary depictions of versions of the devices described herein comprising multiple space-filling implants.

Fig. 21A and 21B are illustrative depictions of a suitable holder for use with the devices described herein.

Fig. 22A and 22B are illustrative depictions of suitable versions of delivery devices for use with the devices described herein.

Fig. 23A-23C and 24A-24C depict an exemplary method of delivering a tissue-piercing device to tissue.

Fig. 25A-25D illustrate a depiction of a version of a device for clamping or restraining tissue.

FIGS. 26A and 26B illustrate a version of the device that includes a patch (patch).

Detailed Description

Palatine tonsils ("tonsils") and pharyngeal tonsils ("adenoids") are masses of lymphoid tissue that assist the body in defending against infection. FIGS. 1A-1C illustrate the dissection of tonsils and adenoids and their surroundings. As shown in FIG. 1A, the tonsils are located in the laryngeal portion of the pharynx and are visible through the mouth. Showing the palatine tonsils (100), palatopharyngeal arch (102), and palatoglossal arch (104). The palatopharyngeal arch (102) includes a mucosa overlying a palatopharyngeal muscle, and the palatoglossal arch (104) includes a mucosa overlying a palatoglossus muscle. The palatoglossus and palatopharyngeus muscles and the superior constrictor muscles form the tonsillar fossa. FIG. 1B shows a perspective view of the tonsillar fossa. The superior constrictor muscle (106), palatoglossus muscle (108), and palatopharyngeus muscle (110) are shown. The glossopharyngeal nerve (112) is also shown, located in the outer wall of the pharynx (not shown) below the upper constrictor muscle (106). Typically, the glossopharyngeal nerve (112) is the cranial nerve that innervates the tonsils and part of the tongue.

The tonsillar fossa forms the "tonsillar bed" for the tonsils, and the tonsils are connected thereto. In particular, the tonsils are located on the superior constrictor muscle (106) and are bounded posteriorly by the palatopharyngeal muscle (110) and anteriorly by the palatoglossus muscle (108). During a tonsillectomy, the surgeon separates at least a portion of the tonsils from the muscles of the tonsillar fossa while attempting to minimize trauma to the tonsillar fossa. The glossopharyngeal nerve may be damaged if the tonsillar bed is pierced during a tonsillectomy. Once the tonsils are removed, one or more portions of the mucosa of the palatopharyngeal or palatoglossal arch ("mucosal valves") may be pulled out of the exposed tissue and sutured into place, thereby sealing the surgical site.

Adenoids, on the other hand, are located behind the nasal passages in the nasopharynx. Fig. 1C shows a sagittal cross-section of a portion of the head and throat. Showing a nasopharynx (114) that houses adenoids (116). A palatopharyngeal arch (118) and palatoglossal arch (120) below the soft palate (122) and surrounding the tonsils (124) are also shown. Adenoidectomies are similar to tonsillectomies in that the adenoids are separated from the surrounding tissue and removed through the mouth.

Generally, described herein are devices and methods for treating one or more regions of tonsil tissue. When the term "tonsillar tissue" is referred to herein, it should be understood that the tonsillar tissue can include, without limitation, any portion of the palatine tonsils, adenoids, lingual tonsils, eustachian tube tonsils, tonsillar fossa (e.g., palatopharyngeal arch, palatoglossal arch, superior constrictor muscle), or other peripheral tissue (e.g., muscle, fascia, connective tissue). In some cases, the devices described herein may be used to treat one or more inflamed or infected tonsils. In other cases, the devices and methods may assist in recovery after tonsil procedures. When the term "tonsillar surgical procedure" is referred to herein, it should be understood that the tonsillar surgical procedure can include, without limitation, any procedure such as a tonsillectomy, adenoidectomy, tonsillar tonsillectomy, other treatment of sleep apnea, tonsillitis, or other tonsillar conditions, and the like. The devices and methods may help minimize post-operative pain or discomfort, may help prevent post-operative infection or bleeding, may shorten healing or recovery time, may achieve a combination of the above, and the like.

Device for measuring the position of a moving object

Described herein are devices for treating one or more portions of tonsil tissue. In certain aspects, the device may be used to treat tonsil tissue during or after a tonsil procedure. The device may, but need not, release one or more drugs or agents to tonsil tissue. The terms "drug" or "agent" are used interchangeably throughout, and it is understood that the drug or agent may include, without limitation, any suitable chemical species or compound, whether active or inert. In addition, the device may or may not be designed to be biodegradable, bioerodible, or otherwise degradable. In some aspects, one or more portions of the device may be implanted in tissue. In certain such aspects, one or more portions of the device may be designed to perforate, pierce, or penetrate tissue. In other aspects, one or more portions of the device may be designed to shield or cover one or more regions of tonsil tissue. In other versions, the device may be designed to fixate, stretch, compress, stretch, approximate, or otherwise manipulate tissue.

The device may have any suitable size, shape or configuration of elements. In certain aspects, one or more portions of the device can be solid. In other aspects, one or more portions of the device may be semi-solid. The device or one or more elements thereof may include, without limitation, one or more sutures, threads, bands, filaments, fibers, rods, tubes, spikes, staples, clips, gels, foams, creams, beads, patches, meshes, flaps, sheets, films, combinations thereof, and the like. These various devices and components will be described in greater detail below.

Any of the devices described herein may be delivered to tonsil tissue in any suitable manner. In certain aspects, at least a portion of the device is implanted in tissue. In some such arrangements, the entire device may be implanted in tonsillar tissue. In other versions, one or more portions of the device may be implanted into tonsillar tissue. In some such arrangements, different portions of the device may be implanted into different regions of tonsil tissue. For example, in some versions, one or more portions of the device may be implanted in tissue of the palatoglossal arch while another portion of the device may be implanted in tissue of the palatopharyngeal arch. When a portion of the device is implanted in tissue, the portion may be placed within an opening or void in the tissue, under the tissue, between the tissues, or a combination thereof. When the device is placed in an opening or void within tissue, the opening or void may be naturally occurring or artificially created. In other aspects, at least a portion of the device may be placed on, against, near, or adjacent to tissue. In these arrangements, the device portion may be held in place in any suitable manner. In some aspects, one or more portions of the device or separate components may be used to anchor the device to tissue. In other versions, one or more portions of the device adhere to tissue. In other aspects, the peripheral tissue may be treated to wrap around or engage one or more portions of the device. For example, if the mucosal valve is pulled out and sealed to cover the exposed tonsillar tissue during a tonsillectomy, the mucosal valve may be used to cover at least a portion of the device. In other cases, the palatoglossal arch and the palatopharyngeal arch may be brought into and maintained in proximity to each other, which may help to clamp portions of the device between the arches.

Suture line

In certain aspects, one or more sutures or suture-like materials (e.g., yarns, threads, strings, bands, etc., collectively referred to herein as "sutures") may be delivered to the tonsillar tissue. The suture may or may not be designed to deliver one or more drugs to the tonsillar tissue. As will be described in greater detail below, when the suture delivers one or more drugs, the suture may deliver the drugs in any suitable manner. In addition, the suture may or may not be designed to be biodegradable, bioerodible, or otherwise degradable. The suture may additionally include one or more features to aid in placement or retention in tissue. For example, in some versions, the suture may itself be anchored within the tissue. More specifically, the suture may contain one or more unidirectional anchors, flaps, barbs, or other means of causing the suture to be pulled through tissue in one direction, but not moved in the opposite direction. In this way, the suture may be passed at least partially through one or more regions of tonsil tissue, but may remain unretracted from the tissue.

One or more sutures may be applied to the tonsillar tissue in any suitable manner. In some cases, one or more sutures may be used to anchor or attach at least portions of one or more devices to tissue. In other cases, one or more sutures may be used to join or connect two or more regions of tissue. For example, one or more of the sutures described above may be used to suture the mucosal valve in situ when the valve is pulled over the exposed tonsil tissue. In other cases, one or more sutures may be used to approximate or reduce the distance between the palatoglossal arch and the palatopharyngeal arch. This may help open the airway to the throat and may further assist in the treatment of respiratory disorders such as obstructive sleep apnea. In other cases, one or more sutures may be sutured, advanced, or placed through one or more regions of tonsil tissue. In a version where one or more sutures are caused to release one or more drugs, the sutures are caused to provide the drugs to those regions of tonsil tissue, either by placement in or through one or more tissues. To place the suture in the tissue region, the suture may be attached to a needle or other structure, and the needle or other structure may be pulled through the tissue volume, thereby bringing the suture thereto. In other cases, the distal end of a cannula or tube (e.g., hypotube) may be pushed into the tissue volume and a length of suture can be extended from the cannula or tube into the tissue. Device for piercing tissue

In certain versions of the devices described herein, the devices may be designed to pierce, perforate, or penetrate tonsil tissue. However, it should be understood that while these tissue-piercing devices can penetrate tissue, they need not actually be used to penetrate tissue. In some cases, one or more tissue-piercing devices may be held against an area of tissue by one or more flaps, meshes, films, or sheets (such as those described below). When used to penetrate tissue, the tissue-piercing device may penetrate tissue in order to facilitate implantation of tonsil tissue.

Each tissue-piercing device may have any suitable size, shape, and configuration of elements. The tissue-piercing device may or may not be designed to release one or more drugs. As will be described in greater detail below, the tissue-piercing device, when designed to release one or more drugs, may release any suitable drug in any suitable manner. Further, the tissue-piercing device may or may not be designed to be biodegradable, bioerodible, or otherwise degradable, and may be made of any suitable material or combination of materials, such as those described below. The means for piercing tissue may be substantially rigid, but need not be. Indeed, one or more portions of the device that pierce tissue may be bendable. In some aspects, the tissue-piercing device may comprise one or more bendable sections and one or more rigid sections.

Figures 2A-2K illustrate several suitable versions of a device for piercing tissue. Fig. 2A illustrates one version of a tissue-piercing device (200) comprising a filament (202). For the filament (202) shown in fig. 2A, any suitable rod, fiber, tube, or rod-like structure may be used. The tissue-piercing device (200) may be inserted into tissue by pushing an end of the tissue-piercing device (200) toward the tissue. Although shown in fig. 2A as having a circular cross-section, the filaments (202) may have any suitable cross-sectional shape, such as oval, triangular, rectangular, polygonal, or irregular geometric shapes. Further, while the wire shown in fig. 2A is straight, the wire (202) need not be so. In practice, the wire (202) may have one or more curves, bends, twists or kinks. For example, fig. 2B illustrates a version of a tissue-piercing device (204) that includes a curved wire (206). In these aspects, the curved wire (206) may have any suitable radius of curvature. In addition, the curved configuration may reduce the depth that a tissue-piercing device (204) may pierce. For example, when placing a tissue-piercing device (204) in a tonsil bed, it may be desirable to limit the depth of penetration, thereby reducing the likelihood that the tissue-piercing device (204) will penetrate or damage one or more nerves (e.g., glossopharyngeal nerve) or blood vessels (e.g., carotid artery).

Fig. 2C illustrates another version of the tissue-piercing device (208) comprising a wire (210), the wire (210) being wound into a coil having a loop (212). In these versions, the coiled wire (210) may contain any number of loops (212), and each loop (212) may have any suitable diameter. The coiled wire (210) may take on any suitable overall shape. In some versions, coiled wire (210) may be wound generally in a cylindrical shape, such as tissue piercing device (208) shown in fig. 2C. In other versions, the coiled wire (210) may be wound generally in a conical or frustoconical shape, or may be wound in an hourglass shape.

Although the tissue-piercing device shown in fig. 2A-2C has a constant cross-sectional area, it is not required. Indeed, the cross-sectional area of the device that pierces the tissue may vary for one or more portions of the device. Fig. 2D illustrates one version of a tissue-piercing device (214) comprising a wire (216) having a tapered end (218). The tapered end (218) may assist the tissue-piercing device (214) in piercing, perforating, or penetrating tissue. In other versions, the cross-sectional area of the tissue-piercing device may vary along its entire length. Fig. 2E and 2F show side and perspective views, respectively, of one such version of a tissue-piercing device (220). A spike (222) is shown, which decreases in cross-sectional area from a proximal end (224) to a distal end (226) thereof. The reduced cross-sectional area of the distal end (226) may assist the tissue-piercing device (220) in piercing, perforating, or penetrating tissue.

The tissue-piercing device may be solid or may be at least partially hollow. Indeed, the tissue-piercing device may contain one or more holes, voids, channels or other spaces within the body of the device. Fig. 2G shows a side view in cross-section of one such aspect of a tissue-piercing device (228) including a spike (230) having a void (232) therein. The tissue-piercing device (228) may contain any number of voids (232), and each void (232) may have any suitable size, shape, and location within the tissue-piercing device (228). In versions where the tissue-piercing device (228) comprises one or more voids (232), the one or more voids (232) may serve as reservoirs for one or more solutions, powders, solids, foams, gels, or combinations thereof, which may or may not contain one or more drugs.

In the case where the cavity (232) contains one or more drugs or drug-containing materials, the one or more drugs may diffuse or migrate from the cavity (232) through the body of the tissue-piercing device (228). In embodiments where the tissue-piercing device (228) is designed to be biodegradable, bioerodible, or otherwise degraded, degradation of the device (228) may expose one or more portions of the cavity (232). Once exposed, the one or more drugs or materials may be released from the cavity (232). Fig. 2H illustrates another version of a tissue-piercing device (234) comprising a spike (236) having a cavity (238) and a channel (240) therein. In these aspects, one or more channels (240) may penetrate the body of the spike (236) from the void (238). In some cases, one or more drugs or materials contained in the cavity (238) may exit the tissue-piercing device (234) through one or more channels (240). The tissue-piercing device (234) may contain any number of channels (240), and each channel (240) may have any suitable size or cross-sectional shape. The number of channels (240), the size and shape of each channel (240), and the nature of the drug or material contained in the cavity (238) may determine the rate at which the drug or material exits the tissue-piercing device. For example, increasing the cross-sectional area of the channel (240) may increase the rate at which material can pass through.

The tissue-piercing device may additionally include one or more elements designed to engage one or more surfaces. For example, fig. 2I and 2J show side and perspective views, respectively, of a tissue-piercing device (242) having spikes (244) and a base member (246). When the spikes of (244) of the tissue-piercing device (242) are implanted in tonsillar tissue, the base member (246) may press against or engage one or more tissue surfaces (not shown). In effect, the base member (246) may act as a stop, limiting the depth to which the spike (244) can penetrate. When the spike (244) penetrates the tonsillar bed or peripheral tissue, limiting the depth of penetration may reduce the likelihood that the spike (244) may penetrate sufficiently deep to damage one or more nerves (e.g., glossopharyngeal nerve) or blood vessels (e.g., carotid artery). For example, in certain aspects, the penetration may be less than about 5mm, less than about 4mm, less than about 3mm, less than about 2mm, and the like. As will be described in greater detail below, in versions where tissue-piercing device (242) is used to anchor one or more devices to tonsil tissue, base member (242) may engage one or more portions of one or more devices to hold one or more devices against tissue.

The base member may be any structure suitable for engaging a tissue surface and may have any suitable size or shape. Although shown in fig. 2I and 2J as circular plates, the base member may be a plate having any suitable shape. In certain aspects, the base member may comprise an oval, triangular, rectangular, polygonal, or irregularly shaped plate. In other aspects, the base member may not be a plate at all. Indeed, in certain aspects, the base member may comprise a sphere, hemisphere, pyramid, box, cube, or irregular geometric shape. Further, the base member may include one or more voids or spaces, such as described above. Fig. 2K illustrates a side view in cross-section of one version of a tissue-piercing device (248). A spike (250) and a spherical base member (252) are shown, each containing a cavity (254 and 256, respectively). Cavities (254) and (256) may be independent or may be connected by one or more holes or channels (not shown).

In some aspects, the tissue-piercing device may include one or more components that may help keep the tissue-piercing device implanted in the tissue. In certain aspects, the overall shape of the tissue-piercing device may help keep the tissue-piercing device implanted in the tissue, such as the coiled wire (210) shown in fig. 2C. Fig. 3 illustrates another version of a device (300) for piercing tissue. A wire (302) having a notch (304) is shown. The notch (304) may allow the tissue-piercing device (300) to pass through tissue in one direction, but may prevent movement in the opposite direction. The tissue-piercing device (300) may contain any suitable number of notches (e.g., 0, 1, 2, 3, 4, 5, or 6 or more), and each notch may be of any suitable size and location on the tissue-piercing device (300). The amount that the tissue-piercing prevention device (300) is pulled out of the tissue may depend in part on the number of notches (304) and the size of each notch (304). For example, increasing the number of notches (304) may make it more difficult to remove a tissue-piercing device from tissue after it has been implanted. The recess (304) may be formed in any suitable manner, such as cutting or etching the surface of the tissue-piercing device (300).

In other aspects, the tissue-piercing device comprises one or more barbs, prongs, or protrusions that allow the tissue-piercing device to move in a single direction in the tissue. Fig. 4A shows one version of a tissue piercing device (400) comprising a spike (402), the spike (402) comprising a barb (404). Although shown as having only one barb (404) in fig. 4A, the tissue-piercing device (400) may have any suitable number of barbs (e.g., 0, 1, 2, 3, or 4 or more). Indeed, fig. 4B shows one version of a tissue piercing device (406) comprising a filament (408) with 2 barbs (410). Fig. 4C shows another version of the tissue-piercing device (412) including angled prongs (414). In other versions, such as the version shown in fig. 4D, the tissue-piercing device (416) includes threads (418). The threads (418) may rotate the tissue-piercing device (416) into tissue such that the threads (418) engage the tissue. The engagement between the threads (418) and the tissue may help prevent the tissue-piercing device (416) from being pulled out of the tissue.

In some aspects, the tissue-piercing device may comprise one or more staples. The staples may be of any size or shape depending on their intended use. Fig. 5 illustrates a suitable version of a device (500) for piercing tissue. A staple (502) including a base (504) and legs (506) is shown. The base (504) and legs (506) may be formed from a single piece of material or may be formed from a plurality of separate pieces connected. Further, one or more portions of the staple (502) (e.g., the base or portions thereof, the legs or portions thereof, etc.) may be rigid, while one or more other portions of the staple (502) may be bendable.

Generally, the legs (506) may be designed to pierce tonsillar tissue. In some aspects, one or more of the legs (506) may include one or more barbs, prongs, notches, or other structures that help hold the leg (506) in place once implanted in tissue. Further, while shown as straight in FIG. 5, the legs (506) need not be. In practice, one or more of the legs (506) may be curved. In some such arrangements, one or more of the legs (506) may be curved inwardly. Fig. 6A and 6B illustrate one aspect of a tissue piercing device (600) comprising a staple (602) having a base (604) and inwardly bent legs (606). To implant the staple (602) into tissue, the base (604) may be bent and the ends of the legs (606) may be placed adjacent tonsil tissue (608), as shown in fig. 6A. The base (604) may then be unbent, which may then drive the legs (606) into the tonsil tissue (608), as shown in fig. 6B. Once implanted in tissue (608), the curved legs (606) may help prevent the staple (602) from pulling out of the tissue (608). In addition, the curved legs (606) may reduce the overall depth of penetration of the staple (602), which may reduce the likelihood of the staple (602) damaging one or more sensitive structures, such as the glossopharyngeal nerve. Similarly, fig. 7A and 7B illustrate another version of a tissue piercing device (700) comprising a staple (702) having a base (704) and outwardly bent legs (706). To implant the staples (702) into the tissue (708), the base may be bent and the ends of the legs (706) may be placed adjacent the tonsil tissue (708), as shown in fig. 7A. The base (704) may then be unflexed, which may then drive the legs (706) into the tonsil tissue (708), as shown in fig. 7B.

Although shown in figures 5, 6A, 6B, 7A and 7B as having 2 legs, the staple may have any suitable number of legs (e.g., 2, 3, 4 or 5 or more). For example, fig. 8 shows one version of a tissue piercing device (800) including a staple (802) having 3 legs (804). Although 3 legs (804) are shown in fig. 8 as being inwardly curved, each leg (804) may be straight, outwardly curved, or have some alternative configuration. Each leg (804) may have the same configuration, or may have a different configuration.

Clamp

Certain versions of the devices described herein may comprise one or more clips. Typically, each clip comprises a surface member and one or more anchor members and is affixed to the tonsillar tissue by at least partially implanting the one or more anchor members into the tissue. This may be accomplished by pushing the clip against the tonsil tissue so that the anchoring member enters the tissue. In certain aspects, one or more portions of the clip may be designed to release one or more drugs. When the clip is designed to release one or more drugs, it may be implemented in any suitable manner, such as those described in more detail below. Further, the clip may or may not be designed to be biodegradable, bioerodible, or otherwise degradable.

Fig. 9A and 9B show perspective and side views, respectively, of one such version of clip (900). A surface member (902) and an anchor member (904) are shown. The surface member (902) is typically held on or over the tonsil tissue surface, while the anchor member (904) may pierce, perforate, or penetrate the tonsil tissue to attach the clip (900) thereto. In addition, the surface member (902) may protect exposed tonsil tissue from irritation, force, or substances that may come into contact with tonsil tissue. Although shown in fig. 9A and 9B as circular plates, the surface member (902) may be any suitable size or shape. In some aspects, the surface member (902) may be oval, square, rectangular, triangular, polygonal, or may have an irregular shape. Further, while shown as flat in fig. 9A and 9B, the surface member (902) need not be so. Indeed, the surface member (902) may comprise one or more ridges, undulations, flanges, rough surfaces, or the like. The surface member (902) may be rigid or may be bendable. In some aspects, the surface member (902) may have one or more rigid portions and one or more bendable portions.

The anchor member (904) may have any suitable size, shape and configuration of elements. As shown in fig. 9A and 9B, the anchor member (904) may include a post (906) with a barb (908). Similarly, the anchoring member (904) may comprise any suitable structure including, without limitation, struts, barbs, spikes, hooks, curved legs, combinations thereof, and the like. Fig. 10A and 10B illustrate top and bottom perspective views, respectively, of one aspect of a clip (1000). A surface member (1002) and an anchor member (1004) comprising a V-shaped barb (1006) are shown. A reinforcement member (1008) is also illustrated, which may be any suitable structure (e.g., a bar, a rod, a plate, etc.) capable of providing structural reinforcement to at least a portion of the face member (1002). FIG. 11A illustrates another version of a clip (1100). A surface member (1102) and an anchoring member (1104) comprising curved legs (1106) are shown. The curved legs may help anchor clip (1100) to tissue while reducing the depth of penetration of anchoring member (1104). Although shown in fig. 11A as being curved outwardly, the curved legs (1106) may be curved inwardly. Further, the clip may have a combination of the anchoring devices described herein. Fig. 11B illustrates one such version of a clip (1108) that includes a face member (1110), curved legs (1112), and barbed legs (1114).

The surface member and the anchoring member may be, but need not be, made from a single piece of material. Indeed, in certain aspects, one or more of the sutures or tissue-piercing devices described above may be used to anchor the surface member to the tissue. In some aspects, a suture (or needle attached thereto) or tissue-piercing device may be used to pierce one or more portions of the surface member. In another aspect, the surface member may include one or more holes through which sutures or tissue-piercing devices may be passed to anchor the surface member to the tonsil tissue. Fig. 12 illustrates one such version of a clip (1200). A surface member (1202) comprising an aperture (1204) is shown. Also shown is a staple (1206) having legs (1208) passing through 2 holes (1204).

Tissue restraint device

In certain versions of the devices described herein, the devices may be designed to stretch, fixate, tighten, reposition, or restrict tonsil tissue changes. Fig. 13A-13D illustrate such an apparatus (1300). Fig. 13A shows a perspective view of a device (1300) comprising a body member (1302) and an anchor (1304). Fig. 13C shows a side view of the device (1300) implanted in tonsil tissue (1306), where the anchor (1304) is at least partially inserted into the tonsil tissue (1306) at the penetration site (1308). FIG. 13D shows a perspective view of the device (1300) implanted between the palatoglossal arch (1314) and the palatopharyngeal arch (1316).

Once the region of tonsil tissue (1306) is implanted, the device may function to limit the movement of the tissue. Typically, the body member (1302) is made of a material that is capable of bending or folding back from its original shape when subjected to one or more forces or stimuli, but tends to return to its original shape when the force or stimulus is removed. The original shape of the body member (1302) may be flat or may include one or more arcs or bends. Certain actions (i.e., swallowing) may cause tonsil tissue to move, shift, or deform, which may lead to pain or discomfort in certain circumstances (e.g., after a tonsillectomy). As shown by arrows (1310) in FIG. 13C, this movement may cause the tonsil tissues (1306) between the penetration sites (1308) to move toward one another, which may cause the body member (1302) to bend or fold back. The tendency of the body member (1302) to return to its original shape may resist this bending or folding back. This resistance may thus cause the device (1300) to provide one or more forces (1312) to the tonsil tissue (1306) at the penetration site (1308). These forces (1312) may help keep the tonsil tissue (1306) stretched, and may prevent other movement of the tonsil tissue (1306). This may therefore help to minimise the pain or discomfort experienced by the patient.

In addition, the tendency of the body member (1302) to return to its original shape may assist in the implantation of the retention device (1300) within tonsil tissue (1306). As shown in fig. 13B, the body member (1302) may be slightly flexed prior to inserting the anchor (1304) of the device (1300) into the tonsil tissue (1306). The anchor (1304) may then be inserted into tissue (1306), and the tendency of the body member (1302) to return to its original shape may move the anchor (1304) into the tonsillar tissue (1306). This may result in the device constantly applying one or more forces to the tissue, which may thus maintain the tonsil tissue (1306) in a stretched configuration.

While shown in fig. 13A-13D as being rectangular, the body member (1302) may have any suitable size or shape. For example, fig. 14 illustrates one aspect of an apparatus (1400) comprising a square body member (1402) and an anchor (1404). Other suitable body member shapes include, without limitation, circular, oval, triangular, polygonal, irregular geometric shapes, and the like. Although shown in fig. 13A-13C as having anchors (1304), the device (1300) need not be so. In versions that do include anchors (1304), the device (1300) may contain any number of anchors (e.g., 1, 2, 3, 4, 5, 6, or 7 or more). Each anchor (1304) may have any suitable size, shape, or dimension. In some versions, the anchor may comprise a single spear point, as shown in fig. 13A-13C. In other versions, the anchor may contain 2 or more spears as shown in fig. 14. In other aspects, the anchor may comprise one or more barbs, spears, thorns, hooks, or other structures capable of securing the body member to tissue.

In embodiments that do not include anchors, the body member may be attached to the tonsillar tissue by any suitable method. Fig. 15 shows one version of an apparatus (1500) comprising a body member (1502) and a wound covering (1504). In general, the wound covering (1504) is attached to tissue to anchor the device (1500) to tonsil tissue (not shown). This can be done in any suitable way. In some aspects, one or more wound dressings (1504) may be sewn into or onto tissue. In other aspects, one or more of the wound coverings (1504) may include one or more adhesives that attach the wound covering (1504) to tissue. In other aspects, one or more of the tissue-piercing devices described above may be inserted at least partially into one or more wound dressings (1504) to anchor the wound dressings to the tissue. Each wound covering (1504) may be made of any suitable material, such as a woven or non-woven mesh.

Fig. 16A and 16B illustrate another suitable version of an apparatus (1600) comprising a body member (1602). Fig. 16A shows a perspective view of a body member (1602) that includes one or more apertures (1604). As shown in the side view of fig. 16B, the aperture (1604) may be designed so that at least a portion of one or more anchoring devices (1606) may pass through it, thereby holding the end (1608) of the body member (1602) against the tonsil tissue (1610). Anchoring device (1606) may be of any suitable construction, such as one or more of the tissue-piercing devices described above. The body member (1602) may contain any number of apertures (1604) (e.g., 1, 2, 3, 4, 5, 6, or more), but the number of anchoring devices (1606) used need not match the number of apertures (1604). In some cases, one or more of the holes (1604) may not be filled, or a single anchoring device (1606) (e.g., a double pointed staple) may pass through the plurality of holes (1604).

While the arrangement shown in fig. 13A-16B is designed to apply force to tonsil tissue in two directions, the body member may be designed to apply force in any number of directions. Fig. 17 illustrates one such version of device (1700) in which body member (1702) applies force to tonsil tissue (not shown) in 3 directions. As shown, the body member (1702) includes 3 arms (1704), each arm having an anchor (1706). Each arm is capable of applying one or more forces to tonsil tissue when implanted in tissue (not shown). Although shown in fig. 17 with anchors (1706), each arm may be attached to tissue in any suitable manner as described above. Further, body member (1702) can have any suitable number of arms (e.g., 1, 2, 3, 4, 5, or more).

Fig. 18A and 18B illustrate another suitable version of the apparatus (1800). A body member (1802) is shown that includes an arm (1804), an anchor (1806), and a flap (1808). While shown as having 4 arms (1804), the body member (1802) may have any suitable number of arms, and each arm may be attached to tissue in any suitable manner, as described in more detail above. In addition, a flap (1808) may span between adjacent arms (1804) and may serve to cover tissue. In this way, the device (1800) may help protect exposed tonsil tissue from contact with one or more substances that may irritate the tissue or cause pain to the patient. The flap (1808) may be made of any suitable material including, without limitation, one or more webs, membranes, or sheets.

In other aspects, one or more devices may be designed to compress tissue or pull two or more regions of tissue toward one another. For example, FIGS. 25A-25D illustrate one aspect of the device (2500). Fig. 25A and 25B illustrate a top perspective view and a bottom perspective view, respectively, of a device (2500) comprising a base portion (2502) and a wing (2504). The device (2500) can be designed such that it can hold tissue between the wings (2504). For example, as shown in fig. 25C, the device (2500) can be placed in the throat such that the device (2500) holds the palatoglossal arch (2506) and palatopharyngeal arch (2508) between the wings (2504). In these versions, device (2500) may maintain one or more portions of the palatoglossal arch (2506) and palatopharyngeal arch (2508) in closer proximity. In some aspects, the device (2500) can further retain one or more additional devices (not shown) between the arches.

Further, in certain aspects, device (2500) can comprise one or more additional structures to help maintain device (2500) in place relative to tissue. For example, as shown in fig. 25D, in certain aspects, wings (2504) of device (2500) may comprise one or more barbs (2510). These barbs may anchor or engage peripheral tissue to help hold the device (2500) in place. Although shown in fig. 25D as including barbs (2510), the device may include any structure suitable for improving engagement between the device (2500) and tissue, such as hooks, spikes, prongs, and the like.

Space filling implant

In some aspects, the devices comprise one or more space-filling implants. The space-filling implant may be of any suitable construction, such as a tablet, a pellet, a bead, a capsule, a microsphere, a microcapsule, combinations thereof, and the like. Typically, a plurality of these space-filling implants may be used to at least partially fill one or more cavities, or spaces within tissue. For example, fig. 19A and 19B show a plurality of beads (1900) disposed in a space (1902). As shown in fig. 19A, when placed in a space (1902), a plurality of beads (1900) may assemble on themselves to conform to the shape of the space (1902). This self-assembly allows the space-filling implant to fit within spaces (1902) of different sizes and shapes. In addition, one or more gels or foams, such as those described in more detail below, may be used to fill the space to fill any voids between the implants.

In addition, as shown in fig. 19B, when one or more forces (1904) or other stimuli cause a change in the size of space (1902), the plurality of beads (1900) may adjust to accommodate the change. In some aspects, however, the space-filling implant may resist changes in the space (1902) in which it is located. In some versions, the space-filling implants may adhere to each other once implanted, such that the space-filling implants are joined or adhered together after their initial self-assembly. Such adherence can be achieved in any suitable manner, such as covering the space-filling implant with one or more adhesive coatings (e.g., coatings of fibrin glue, cyanoacrylate glue, etc.), or providing one or more stimuli (e.g., heat, light, etc.) that cause adjacent space-filling implants to fuse together. Once the two space-filling implants are connected or adhered together, they may be prevented from movement relative to each other. Thus, when a force or stimulus causes a change in the shape or size of the space, the attached space-filling implant can resist the change.

Although elliptical beads (1900) are shown in fig. 19A and 19B, each space-filling implant may have any suitable shape. For example, a single space-filling implant may be spherical, box-shaped, conical, frustoconical, rod-like, pyramidal, irregular, combinations thereof, and the like. In addition, one space-filling implant may or may not be designed to have the same shape and size as another space-filling implant. As described in more detail below, the space-filling implant may or may not be designed to release one or more drugs, and may or may not be designed to be biodegradable, bioerodible, or otherwise disintegratable.

The space-filling implants described herein may be placed in any suitable space in or around tonsillar tissue and may be delivered by any suitable structure (e.g., a funnel, needle, hypotube, cannula, or other tube-like structure). In some cases, the space may be naturally occurring (e.g., a void between two tissues). In other cases, the space may be artificially formed. For example, one or more channels or voids may be formed during tonsil procedures. Alternatively, one or more spaces may be created (e.g., by inserting a needle, trocar, or other suitable device into tissue) in order to accommodate multiple space-filling implants. In other aspects, multiple space-filling implants may at least partially fill one or more cavities, or other spaces within one of the other devices described above. In other embodiments, the space-filling implant adheres to the tissue and is adjacent to the tissue surface. In other aspects, one or more flaps, nets, films, sheets, etc. may be used to hold the plurality of space-filling implants in place against the tissue. Fig. 20 illustrates one such arrangement, in which the space-filling beads (2000) are held in place against tonsil tissue (2002) by a flap (2004). The patch (2004) may be attached or connected to the tissue in any suitable manner, such as those described below.

In some aspects, one or more space-filling implants comprise a capsule or other structure having one or more voids or spaces formed therein. In these approaches, the space-filling implant may burst or rupture when subjected to a certain force or stimulus (e.g., heat, light, pH change, chemicals, etc.). One or more solutions or substances (e.g., drug-containing solutions, adhesives, etc.) may be placed in these structures to release the solution or substance when the space-filling implant is ruptured. For example, one or more of the space-filling beads (2000) shown in fig. 20 may contain a cavity (not shown) in which an anesthetic or analgesic is contained. When one or more forces or stimuli are applied to the coverslip (2004), such as compressive forces that may occur when swallowing food, these forces or stimuli may cause one or more of the space-filling beads (2000) to rupture. This may release an amount of anesthetic or analgesic that may reduce the sensation of pain in the tonsillar tissue.

In embodiments where one or more of the space-filling implants comprise a capsule or other structure containing cavities, the space-filling implants may be designed to break or rupture at different times. In some aspects, devices of different sizes may rupture at different forces. For example, a device with thicker walls around a cavity may require more force to rupture than a device with thinner walls around a cavity. In versions where the space-filling implant is designed to be biodegradable, bioerodible, or otherwise degraded, the space-filling implant may become more susceptible to breakage over time. Thus, by providing space-filling implants with different degradation times, some space-filling implants may rupture at an earlier time than other space-filling implants. In general, space-filling implants may be designed to break or fracture at different times during a treatment regimen.

In other aspects, the space-filling implant may comprise a capsule designed to break or dissolve to release a substance that solidifies after release. For example, in some versions, different space-filling implants may comprise different compositions of fibrin glue. When the capsules are broken, the components of the fibrin glue may mix to form a solid fibrous matrix so that it may adhere to the surrounding tissue. Generally, a fibrin clot can be formed by mixing fibrinogen and thrombin in an aqueous environment, as thrombin polymerizes the fibrinogen into a polymer matrix. Thus, in these embodiments, some capsules may contain a thrombin solution while others contain a fibrinogen solution. When the capsules are broken or dissolved, these components may combine to form a polymeric fibrin matrix. It will be appreciated that the fibrinogen and thrombin solutions may contain one or more clotting factors or other components (calcium chloride) that may aid in the fibrin polymerization process, and may also contain one or more drugs or agents that may be released from the resulting fibrin matrix.

In other versions, one or more of the space-filling implants may be expandable. These space-filling implants may be any suitable expandable structure, such as an inflated structure (e.g., a balloon) or a swellable implant. The expandable space-filling implant may be delivered to one or more spaces in expanded or unexpanded form, such as those described above. When delivered in an unexpanded form, the expandable space-filling implant may expand in response to one or more forces or stimuli. These forces or stimuli may or may not be designed to be naturally provided by the body. For example, when the space-filling implant comprises one or more swellable materials, the space-filling implant may expand when the space-filling implant is in contact with saliva or other liquids introduced into tonsillar tissue. When the space-filling implant comprises a balloon or other inflatable structure, the balloon may be inflated after delivery to the tonsillar tissue. In some embodiments, the balloon may be filled with a drug-containing solution and designed to allow one or more drugs to flow out over a period of time. In other aspects, the balloon may include one or more elements (e.g., hooks, barbs, etc.) that may anchor the balloon to one or more regions of tonsil tissue. In addition, when one or more expandable space-filling implants expand in or around a space in tonsil tissue, the space-filling implant may apply one or more forces to the surrounding tissue, and in some cases may expand or reshape the surrounding tonsil tissue.

Foams and gels

In certain aspects, one or more gels or foams may be delivered to one or more portions of tonsil tissue. The gel or foam may be applied to the tonsil tissue during or after a tonsil procedure. The gel or foam may provide one or more beneficial functions. As will be described in more detail below, in certain aspects, the gel or foam may deliver one or more drugs to the peripheral tissue. In other arrangements, the gel or foam may help to seal or shield exposed tonsillar tissue or tissue of the exposed tonsillar fossa from external stimuli, such as acidic compounds or other irritating chemicals that may be swallowed when eating or drinking, or from frictional forces or temperature changes resulting from swallowing food or liquids.

Any suitable gel or foam may be used. In certain aspects, the gel or foam may be biodegradable, bioabsorbable, bioerodible, dissolvable or otherwise disintegratable. The gel may be made of any colloidal system in which a porous network of small particles, which may or may not be connected, spans the volume of the liquid medium. The foam may be formed by entrapping one or more gas bubbles in a liquid or solid. In certain aspects, one or more gels or foams may naturally adhere to tissue. For example, when the gel or foam is made of chitosan, chitin, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), fibrin glue or similar materials, the gel or foam may adhere to the tissue.

Where one or more gels or foams are administered to the tissue, they may be administered by any suitable method. In some aspects, one or more gels or foams may be placed in one or more holes, channels, voids, or other spaces within tonsil tissue. These spaces may be naturally occurring or artificially formed. In other cases, one or more gels or foams may be used to cover or encapsulate one or more tissue surfaces. As noted above, in certain aspects, the gel or foam may naturally adhere to the tissue surface. In other aspects, one or more structures may be used to hold the gel or foam in place against the tissue. Indeed, in certain aspects, one or more flaps, films, sheets, or meshes may be used to hold one or more gels or foams against tissue, as described in more detail below. In these approaches, a cover sheet, film, sheet, or mesh may be anchored or attached to the tissue, and one or more gels or foams may be placed under the cover sheet, film, sheet, or mesh. Any suitable cover sheet, film, sheet or web, such as those described herein, may be used. In the case of suturing the mucosal valve to the exposed tonsil bed, one or more gels or foams may be placed under the mucosal valve.

In other embodiments, one or more gels or foams can solidify after delivery. The gel or foam may solidify in response to one or more stimuli (e.g., heat, energy, light, pH change, humidity, chemicals or biological materials, etc.), or may naturally solidify after delivery to the tonsillar tissue. In certain aspects, a gel or foam may be delivered to one or more spaces in or around tonsil tissue, where the gel or foam may solidify. When the gel or foam contains one or more drugs, the gel or foam may be used to create one or more solid drug-releasing agglomerates.

Further, one or more gels or foams may be used in conjunction with one or more of the devices described herein (e.g., a tissue piercing device, a tissue restraining device, a clip, a space filling implant, or a combination thereof). In certain aspects, one or more gels or foams may be used to at least partially encapsulate one of the devices. In other arrangements, one or more gels or foams may be used to fill one or more spaces, cavities, or reservoirs within one of the devices.

Cover sheet, film and web

In some aspects, one or more flaps, sheets, membranes, nets or combinations thereof may be placed in, on or around the tonsil tissue. Any of these devices may or may not deliver one or more drugs to the tonsil tissue. When designed to deliver one or more drugs, the patch, sheet, film or mesh may release the drug in any suitable manner as described below. In addition, one or more portions of these devices may be designed to be biodegradable, bioerodible, or otherwise degradable.

Typically, one or more patches, sheets, membranes, nets or combinations thereof may be applied to the tonsil tissue. In some cases, one or more of these devices may be at least partially implanted in tissue. In other cases, one or more of these devices may be used to cover one or more tissue surfaces. When these devices are used to cover one or more tissue surfaces, a flap, sheet, membrane, or mesh may help protect the tonsil tissue from one or more irritants or chemicals that may irritate the tonsil tissue. In some cases, a flap, sheet, film or mesh may completely or partially enclose some or all of a portion of tonsil tissue to avoid external irritation or chemicals. In other cases, a flap, sheet, film or mesh may serve as a temporary hemostatic barrier. In addition, these flaps, sheets, films or meshes may be used to hold one or more additional devices against the tonsil tissue. In other aspects, the cover sheet, film or mesh may be designed such that blood or one or more components of blood may pass through at least a portion of the device.

These devices may be attached to tonsillar tissue in any suitable manner. In certain aspects, one or more portions of the device may naturally adhere to tissue. For example, when the film or sheet is made of a polymer such as chitosan, chitin, PVP, PVA, etc., the film or sheet may adhere to the tissue. For example, sucralfate may be used to help attach one or more portions of the device to tissue. In other cases, one or more biocompatible adhesives (e.g., fibrin glue or cyanoacrylate glue) may be used to attach one or more portions of the device to tissue. In other cases, one or more sutures or tissue-piercing devices may be used to anchor one or more portions of the device to the tissue. In other cases, one or more additional cover sheets, films, sheets, or webs may cover the device to hold it in place. In other cases, one or more of the clips or tissue-restraining devices described above may be used to anchor one or more portions of the device to tissue.

Any suitable cover, film, sheet or mesh may be given to the tonsil tissue. When a mesh is used, the mesh may be woven or non-woven, and may have any suitable pore size. In certain aspects, the mesh comprises pore sizes sufficient to allow tissue ingrowth. In fact, any cover sheet, sheet or mesh may be used for tissue ingrowth. For example, the coversheet, film, sheet or web may comprise one or more rough or porous surfaces, which may help promote tissue ingrowth.

When the membrane is applied to tissue, the membrane may be pre-formed or may be formed after administration to the tissue. In the case of a film formed after administration, a gel or foam as described above or some other solidifying material may be administered to the tonsil tissue. In certain embodiments, the gel or foam naturally solidifies as a film when placed against tonsil tissue. In other embodiments, the gel or foam cures when one or more stimuli are applied thereto. Examples of suitable stimuli include, without limitation, heat, light, electricity, moisture, chemicals, biological materials (e.g., proteins, enzymes, etc.), and pH changes. In some embodiments, a layer of fibrin glue may be applied to the tissue surface to form a sheet of polymerized fibrin thereon. When the sheet is applied to tonsil tissue, the sheet may be made of any suitable material, such as those described below.

When a tonsil is removed during a tonsillectomy, one or more clots may form on or within the tonsil bed. In some cases, during postoperative recovery from tonsils, large scars may be removed from tonsils tissue, which may lead to potentially problematic bleeding episodes. To help prevent such bleeding, it may be desirable to minimize the size of clots that may form on the tonsil tissue. Thus, it may be desirable for the cover sheet or sheet to contain one or more holes or cells therethrough to help regulate the size of the formed clot. For example, fig. 26A and 26B illustrate one aspect of a cover slip (2600). Cover glass (2600) is shown in fig. 26A, which comprises a frame (2602) and a plurality of defined compartments (2604). As shown in fig. 26B, the cover sheet (2600) may be placed over and adhered to the tonsil bed (2606) or other tonsil tissue during or after a tonsil procedure. When placed against tissue, blood may flow into the chamber (2604) and may form a plurality of smaller scars (not shown). These smaller scars may reduce the likelihood of bleeding. It should be understood that the chamber (2604) can be any suitable size or shape and that the cover (2600) can have a thickness sufficient to allow blood to flow into the chamber (2604).

Drug delivery

Any of the devices described herein can be used to deliver one or more drugs. Each of the devices described herein can be designed to release any suitable amount of drug over any suitable period of time. The number of devices that release the drug, the choice of drug, the timing of delivery, and the total amount of drug released can be determined by the intended treatment regimen, and can be further fine-tuned to meet the specific needs of the individual patient. Each drug delivered should be released at a rate that provides a healthy, safe, and effective dose to the patient, and each drug delivered should be administered at a total dose that is also healthy, safe, and effective.

The devices described herein may deliver one or more drugs in any number of ways. In certain aspects, at least a portion of the device itself comprises one or more drugs. In some cases, the drug may diffuse out of the device or may be released from the device over time. In other cases, the device may contain one or more cavities, channels, pockets, or other spaces from which the drug or drug-containing material may be released. In other embodiments, the device may contain one or more drug eluting layers, clusters, or reservoirs on one or more surfaces of the device.

Any suitable device or portion thereof may release one or more drugs to the tonsil tissue. In certain aspects, one or more drugs may be added to one or more portions of the body of the device. Each drug may be added to the entire body or may be added to only one or more portions of the body. For example, in a version in which the device comprises a staple having two legs as described above, a first medicament may be added to the first leg and a second medicament may be added to the second leg. In some cases, one or more drugs may diffuse out of the device body. In embodiments where one or more portions of the device are biodegradable, bioerodible, or otherwise degradable, one or more drugs may be released when the portions degrade or erode.

In other embodiments, the body of the device may contain one or more cavities, channels, wells, pockets or other spaces that may contain one or more drugs or drug-containing materials. These spaces may contain one or more drugs, one or more medicated solutions, foams, powders, solids, gels, or combinations thereof. In some aspects, one or more drugs may diffuse out of these spaces through the device body. In other versions, the drug or drug-containing material may exit the device through one or more holes or channels in the body of the device. In embodiments where one or more portions of the device are biodegradable, bioerodible, or otherwise degradable, one or more of the spaces may become exposed to tissue as those portions degrade or erode. In these cases, one or more drugs or drug-containing materials may be released from the device when the space becomes exposed to tissue.

In other embodiments, one or more surfaces of the device may comprise one or more drug-releasing layers or agglomerates exposed thereto. The drug-releasing layer or mass may be made of any suitable biocompatible material capable of releasing the drug over a period of time, and may be made by any suitable method. Each device may contain any number of drug-releasing layers or agglomerates (e.g., 0, 1, 2, 3, 4 or more). Each drug-releasing layer may wrap or cover the entire surface of the device, or may cover only one or more selected portions of the device. Furthermore, one drug release layer may be at least partially disposed on one or more additional drug release layers.

In general, the device may be designed to release one or more drugs over a predetermined period of time. The time may be on the order of hours, days, or weeks. The period of drug delivery will likely depend on the nature and amount of drug to be released and the intended treatment regimen. For example, when the device is used to treat one or more symptoms of a tonsillar surgery procedure, the cycle may be between less than about 1 day, between about 1 day to about 21 days, between about 1 day to about 18 days, between about 1 day to about 15 days, between about 1 day to about 12 days, between about 1 day to about 9 days, between about 1 day to about 7 days, between about 1 day to about 5 days, between about 1 day to about 3 days, between about 3 days to about 21 days, between about 3 days to about 18 days, between about 3 days to about 15 days, between about 3 days to about 12 days, between about 3 days to about 9 days, between about 3 days to about 7 days, between about 3 days to about 5 days, between about 5 days to about 21 days, between about 5 days to about 18 days, between about 5 days to about 15 days, between about 5 days to about 12 days, between about 5 days to about 9 days, between about 5 days to about 12 days, between about 9 days to about 9 days, Between about 5 days to about 7 days, between about 7 days to about 21 days, between about 7 days to about 18 days, between about 7 days to about 15 days, between about 7 days to about 12 days, between about 7 days to about 9 days, between about 9 days to about 21 days, between about 9 days to about 18 days, between about 9 days to about 15 days, between about 9 days to about 12 days, between about 12 days to about 21 days, between about 12 days to about 18 days, between about 12 days to about 15 days, between about 15 days to about 21 days, between about 15 days to about 18 days, or between about 18 days to about 21 days. As will be described in more detail below, this cycle may not begin immediately after implantation or administration of the device.

The drug may be, but is not required to be, released from the device at a constant rate. In fact, the device can be designed to have any suitable release rate characteristics. In certain embodiments, the daily amount of drug released may decrease over time. For example, the device may release an amount of drug for a first period of time (e.g., 1 day), and then may release a second amount of drug for a second period of time. Similarly, the amount of drug delivered may be varied any number of times during this period. The amount of drug released may decrease over time, or increase over time and decrease over a different period of time. Moreover, in certain aspects, the device may comprise multiple drug-eluting layers, and each layer may have a different and specific release profile. Of course, it should be understood that each layer may contain, include, or be designed to release one or more drugs or agents therefrom. Each layer may contain, include or be designed to release the same or different drugs or agents therefrom. Similarly, the device body may additionally contain a drug, and the device body may provide a release profile that is different from one or more drug-eluting layers.

In other aspects, the device may comprise one or more barrier layers. These layers may or may not release the one or more drugs and may delay the release of the one or more drugs from the one or more drug-releasing layers or from the device itself. The barrier layer may or may not be a backbone eroding polymer, or may not be a surface eroding polymer. In certain embodiments, the barrier layer may prevent the drug from passing through it. In these embodiments, the barrier layer may provide a period of time during which no drug is released from at least a portion of the drug-releasing layer or from at least a portion of the device. Once the barrier layer has sufficiently degraded or eroded, drug release may begin or continue. In other embodiments, the barrier layer may be permeable to an amount of the drug. In certain such embodiments, the amount of drug that permeates the barrier layer may be less than the amount of drug that would be released from the drug-release layer in the absence of the barrier layer. The barrier layer may thus provide a period of time during which a lesser amount of drug is released from at least a portion of the drug-release layer. Once the barrier layer has sufficiently degraded or eroded, the amount of drug released from the device may increase.

In addition to the baseline release profile of the device, the drug delivery regimens and combinations thereof described above may allow the device to provide a variable drug release profile or provide an initial or delayed burst release. In addition, these approaches may allow the device to provide different drug release profiles that are independent over different times. For example, the device may comprise two drug-releasing layers separated by a barrier layer. The outer drug-release layer may initially release an initial amount of drug and may follow any suitable drug release profile. The barrier layer may then degrade or erode over a period of time during which some or none of the drug is released from the second drug-release layer. Once degradation has been substantially completed, the second drug release layer may then release a second amount of drug over a second period of time, and such release may also follow any suitable drug release profile. As noted above, each drug-release layer can release any suitable amount of any suitable drug over any suitable period of time.

In addition, one or more release rate modifiers may also be used. The release rate modifier may be any suitable biocompatible substance for modifying the rate of drug release from the device. In certain aspects, the release rate modifier may comprise a hydrophilic agent. In certain instances, the release rate modifier is a polyethylene glycol, e.g., a polyethylene glycol having a molecular weight between about 3000 and about 13000, between about 3000 and about 11000, between about 3000 and about 9000, between about 3000 and about 7000, between about 3000 and about 5000, between about 5000 and about 13000, between about 5000 and about 11000, between about 5000 and about 9000, between about 5000 and about 7000, between about 7000 and about 13000, between about 7000 and about 11000, between about 7000 and about 9000, between about 9000 and about 13000, between about 9000 and about 11000, between about 11000 and about 13000, etc. In certain embodiments, the release rate modifier is polyethylene glycol having a molecular weight of about 6000.

As described throughout, the device may be designed to deliver multiple drugs. In certain embodiments, multiple types of drug particles are contained in a single drug-eluting layer or device body. In other embodiments, the device comprises a non-continuous drug-eluting layer having different portions containing different drugs. In these embodiments, the different moieties may have different compositions and thus may also provide different release rates. In other embodiments, multiple drug-eluting layers may be used, wherein each layer contains a different drug or combination of drugs. As mentioned above, the drug delivery mass may also contain different drugs therein, or may collectively release different drugs, rather than being released from the drug eluting layer. In other embodiments, the device itself may release different drugs or combinations of drugs, rather than from the drug eluting layer. Any combination of these approaches may also be used to achieve the desired drug delivery characteristics.

Illustrative reagents

The device may contain any suitable drug or agent, or combination of drugs or agents, and the agent selected will depend primarily on the intended use of the device. The device may comprise one or more diagnostic agents and may also comprise one or more therapeutic agents. For example, diagnostic agents may be used to diagnose the presence, nature, and/or extent of a disease or medical condition in an individual. Conversely, a therapeutic agent can be used to treat or affect one or more diseases, conditions, sensations, or symptoms.

Diagnostic agents include, for example, contrast agents for ultrasound imaging, Magnetic Resonance Imaging (MRI), Nuclear Magnetic Resonance (NMR), Computed Tomography (CT), Electron Spin Resonance (ESR), nuclear medicine imaging, optical imaging, elastography (elastography), fluorescence imaging, Positron Emission Tomography (PET), Radio Frequency (RF), and microwave laser. Diagnostic agents may also include any other agent useful in facilitating diagnosis of a disease or other condition in a patient, whether or not imaging techniques are used.

Examples of specific diagnostic reagents include radiopaque materials, such as iodine or iodine derivatives, such as iohexol and iopamidol. Other diagnostic agents, such as radioisotopes, may be detected by tracking the radioactive emissions. Examples of agents that can be detected by MRI are typically paramagnetic agents, which include, without limitation, gadolinium chelates. Examples of reagents that can be detected by ultrasound include, without limitation, perfluorohexane. Examples of fluorescent agents include, without limitation, indocyanine green. Examples of reagents for diagnostic PET include, without limitation, fluorodeoxyglucose, sodium fluoride, methionine, choline, deoxyglucose, butanol, raclopride, spiroperidinone, bromospiroperidinone, carfentanil, and flumazenil.

The device may also contain any suitable therapeutic agent. Suitable classes of therapeutic agents include, for example, local anesthetics, analgesics (e.g., anti-inflammatory agents, opiates, etc.), vasoconstrictors, anti-allergic agents, anticholinergics, antihistamines, anti-infectives, antiplatelet agents, anticoagulants, antithrombotic agents, anti-scarring agents, antiproliferatives, chemotherapeutic agents, antineoplastic agents, decongestants, hemostatic agents, healing promoters and vitamins (e.g., retinoic acid, vitamin a, dexpanthenol (depaxanthol), vitamin B and its derivatives), hyperosmotics (hypermoplar agents), immunomodulators, immunosuppressants, and combinations and mixtures thereof. It is to be understood that the devices described herein may contain any combination of drugs or agents (e.g., combinations of 2, 3, or 4 or more drugs or agents). For example, the device may contain a combination of local anesthetic and analgesic, a combination of local anesthetic and antibiotic, a combination of local anesthetic and vasoconstrictor, a combination of analgesic and antibiotic, a combination of analgesic and vasoconstrictor, a combination of analgesic and antibiotic, a combination of local anesthetic, antibiotic and vasoconstrictor, and the like.

Examples of local anesthetics suitable for use in the methods and devices described include, without limitation, ropivacaine, mepivacaine, bupivacaine, cocaine, procaine, etidocaine, lidocaine, prilocaine, articaine, amethocaine, benzocaine, butacaine, chloroprocaine, dicaine, meprocaine, metatetracaine, oxocaine, procaine, proparacaine, lidocaine, tetracaine, tropane, cyclomethiocaine, hecocaine, serocaine, articaine, caricaine, cinchocaine, etidocaine, trimetaine, ionocaine, combinations thereof, and the like. Examples of suitable vasoconstrictors include, without limitation, epinephrine, levonoradrenaline, epinephrine derivatives, combinations thereof, and the like.

Anti-infectives generally include antibacterial, antifungal, antiparasitic, antiviral and antibacterial agents. Anti-inflammatory agents typically include steroidal and non-steroidal anti-inflammatory drugs.

Examples of anti-allergic agents that may be suitable for use in the methods and devices described include, without limitation, pyriminoxidilPotassium salt of (A) and (B)Santen corporation), and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof. Examples of antiproliferative agents include, without limitation, actinomycin D, actinomycin IV, actinomycin I₁Actinomycin X₁Actinomycin C₁And dactinomycin (A)Merck corporation). Examples of antiplatelet agents, anticoagulant agents, antifibrinogenic agents, and anticoagulant agents include, without limitation, heparin sodium, low molecular weight heparin, heparin analogs, hirudin, argatroban, forskolin, vapreotide, prostacyclin and prostacyclin analogs, dextran, D-phenylalanine-proline-arginine-chloromethyl ketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibodies, recombinant hirudin, and thrombin inhibitors (R: (R) (R))Biogen corporation), and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof. Examples of healing promoting agents include, without limitation, sirolimus, everolimus, temsirolimus (temsirolimus), and vitamin a.

Examples of cytostatic or antiproliferative agents that may be suitable for use in the methods and devices described include, without limitation, angiopeptins, angiotensin converting enzyme inhibitors, such as captopril (R) ((R))AndBristol-Myers Squibb Co.), cilazapril or lisinopril (Andmerck corporation); calcium channel blockers, such as nifedipine; colchicine; fibroblast Growth Factor (FGF) antagonists, fish oils (omega 3-fatty acids); a histamine antagonist; lovastatin (Merck corporation); monoclonal antibodies, including without limitation antibodies specific for the platelet-derived growth factor (PDGF) receptor; nitroprusside; a phosphodiesterase inhibitor; a prostaglandin inhibitor; suramin; a serotonin blocking agent; a steroid; a thioproteinase inhibitor; PDGF antagonists including, but not limited to, triazolopyrimidines; and nitric oxide, and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof.

Examples of antimicrobial agents that may be suitable for use in the methods and devices include, without limitation, aminoglycosides, chloramphenicol, ansamycins, β -lactams (e.g., penicillins), lincosamides, macrolides, nitrofurans, quinolones, sulfonamides, sulfones, tetracyclines, vancomycin, and any derivative thereof, or combinations thereof. Penicillins suitable for use in the methods and apparatus include, without limitation, oxacillin, amoxicillin, ampicillin, apacillin, aspoxicillin, azlocillin, bacampicillin, benzylpenicillic acid, penicillin G sodium, carbenicillin, methicillin, dicloxacillin, cloxacillin, cyclopenicillin, dicloxacillin, phenoxybenzacillin, flucloxacillin, natacillin, linancillin, maytansillin, methicillin sodium, mezlocillin, ethoxynaphthalenicillin sodium, oxacillin, penicillin G diester, penicillin G ethylamine, penicillin G benzphetamine, benzathine G, penicillin G benzhydrylamine, penicillin G calcium, hydramin G, penicillin G potassium, penicillin G procaine, penicillin N, penicillin O, Penicillin V, benzathine penicillin V, hydrabamine penicillin V, penicillin V mepiquat chloride, ampicillin potassium, piperacillin, penicillins, phenoxypropylpenicillins, quinacrillin, sulbactam, phthaleinicin, temocillin, and ticarcillin.

Antifungal agents suitable for use in the methods and devices include, without limitation, allylamines, imidazoles, polyenes, thiocarbamates, triazoles, and any derivatives thereof. Antiparasitic agents that may be used include, without limitation, atovaquone, clindamycin, dapsone, diiodoquinoline, metronidazole, pentamidine, primaquine, pyrimethamine, sulfadiazine, trimethoprim/sulfamethoxazoleOxazole, trimetrexate, and combinations thereof.

Examples of antiviral agents suitable for use in the methods and devices include, without limitation, acyclovir, famciclovir, valacyclovir, edexuridine, ganciclovir, foscarnet, cidofovir (vistide), ganciclovir (vitrasert), fomivirsen, HPMPA (9- (3-hydroxy-2-phosphonomethoxypropyl) adenine), PMEA (9- (2-phosphonomethoxyethyl) adenine), HPMPG (9- (3-hydroxy-2- (phosphonomethoxy) propyl) guanine), PMEG (9- [2- (phosphonomethoxy) ethyl ] guanine), HPMPC (1- (2-phosphonomethoxy-3-hydroxypropyl) -cytosine), ribavirin, EI (5-ethynyl-1-beta-D-ribofuranosyl imidazole-4-carboxamide), CAR, Pyrazolofuranidin (3- [ beta-D-ribofuranosyl ] -4-hydroxypyrazole-5-carboxamide), 3-deazaguanine, GR-92938X (1-beta-D-ribofuranosyl pyrazole-3, 4-dicarboxamide), LY253963(1, 3, 4-thiadiazol-2-yl-cyanamide), RD3-0028(1, 4-dihydro-2, 3-benzodithiazine), CL387626(4, 4' -bis [4, 6-D ] [ 3-aminophenyl-N- -, N-bis (2-carbamoylethyl) -sulfonylimino ] -1, 3, 5-triazin-2-ylamino-biphenyl- -2- -, 2' -disulfonic acid disodium salt), BABIM (bis [ 5-amidino-2-benzimidazolyl ] -methane), NIH351, and combinations thereof.

Examples of suitable antimicrobial agents for use in the methods and devices include, without limitation, ethanol, chlorhexidine, iodine, triclosan, hexachlorophene, and silver-based agents such as silver chloride, silver oxide, and silver nanoparticles.

Analgesics may include opioids, anti-inflammatory agents and other analgesics. Examples of suitable opioids include, without limitation, codeine, hydrocodone, dihydrocodeine, oxycodone, fentanyl, propoxyphene, meperidine, hydromorphone, thebaine, papaverine, morphine, acetodihydrocodeine, buprenorphine, oxymorphone, cyclobutyloxymorphone, buprenorphine, dihydroetorphine, tramadol, derivatives thereof, combinations thereof, and the like. Anti-inflammatory agents may include steroidal and non-steroidal anti-inflammatory drugs. Examples of suitable steroidal anti-inflammatory drugs include, without limitation, pregnenolone 21-acetate, alclomethasone, aleurone, amcinonide, beclomethasone, betamethasone, budesonide, clomazone, dehydroflurometasone, clobetasol, cortexolone, clomazone, cortexolone, desoximetasone, dexamethasone, diflorasone, diflucortolone, vindiflunisal, glycyrrhetinic acid, fluzacort, fluorodichloropines, diflunisal, flunisolone, fluocinolone, fluocinonide, fluocortolone, fluccortolone, fluorometholone acetate, fluocinolone acetate, flurandrone, fluorohydropyroxolone acetonide, fluticasone propionate, flucetolone, halcinonide, halobetaxolone propionate, clodimexolone, prednisolone, haloacetate, prednisolone haloacetate, hydropyrone, Hydrocortisone, loteprednol etabonate, methylprednisolone, medroxyprogesterone, methylprednisolone, mometasone furoate, paramethasone, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednisolone valerate, methylprednisolone, rimexolone, mercaptohydrocortisone, triamcinolone acetonide, any derivative thereof, and combinations thereof.

Examples of suitable non-steroidal anti-inflammatory drugs include, without limitation, COX inhibitors. These COX inhibitors may include COX-1 or COX non-specific inhibitors, such as salicylic acid derivatives, aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, sulfasalazine, and azosalicylic acid; para-aminophenol derivatives, such as acetaminophen; indole and indene acetic acids such as indomethacin and sulindac; heteroaryl acetic acids such as tolmetin, diclofenac, and ketorolac; arylpropionic acids such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen and oxaprozin; anthranilic acids (fenamates), such as mefenamic acid and meloxicam; enolic acids, such as the oxicams (piroxicam, meloxicam) and the alkanones, such as naproxone. COX inhibitors may also include selective COX-2 inhibitors, such as diaryl substituted furanones, e.g., rofecoxib; diaryl substituted pyrazoles, such as celecoxib; indoleacetic acids, such as etodolac and sulfonanilides, such as nimesulide).

Examples of chemotherapeutic/antineoplastic agents that may be used in the devices described herein include, without limitation, antineoplastic agents (e.g., cancer chemotherapeutic agents, biological response modifiers, angiogenesis inhibitors, hormone receptor blockers, cryotherapeutic agents, or other agents that disrupt or inhibit tumorigenesis or tumorigenesis), such as alkylating agents or other agents that directly kill cancer cells by attacking their DNA (e.g., cyclophosphamide, ifosfamide), nitrosoureas, or other agents that kill cancer cells by inhibiting changes necessary for cellular DNA repair (e.g., carmustine (BCNU) and lomustine (CCNU)), antimetabolites or other agents that block cancer cell growth by interfering with certain cellular functions, typically DNA synthesis (e.g., 6-mercaptopurine and 5-fluorouracil (5FU), antitumor antibiotics, and other compounds that act by binding or inserting DNA and preventing RNA synthesis (e.g., doxorubicin, adriamycin, and the like, Daunorubicin, epirubicin, idarubicin, mitomycin-C and bleomycin), plant (vinca) alkaloids and other anti-neoplastic agents derived from plants (e.g., vincristine and vinblastine), steroid hormones, hormone inhibitors, hormone receptor antagonists and other agents that affect the growth of hormone-responsive cancers (e.g., tamoxifen, herceptin, aromatase inhibitors (e.g., aminoglutethimide and formestane), triazole inhibitors (e.g., letrozole and anastrozole), steroid inhibitors (e.g., exemestane)), anti-angiogenic proteins, small molecules, gene therapy and/or other agents that inhibit angiogenesis or vascularization of tumors (e.g., meth-1, meth-2, thalidomide), bevacizumab (Avastin), squalamine, endostatin, Angiozyme, AE-941 (neostat), CC-5013(Revimid), medi-522(Vitaxin), 2-methoxyestradiol (2ME2, Panzem), Carboxyamidotriazole (CAI), combretastatin A4 prodrug (CA4P), SU6668, SU11248, BMS-275295, COL-3, EMD121974, IMC-1C11, IM862, TNP-470, celecoxib (Celebrex), rofecoxib (Vioxx), interferon alpha, interleukin-12 (IL-12) or Science Vol, 1197, 1201 p.2000 (8.17.2000) (which is expressly incorporated herein by reference), any of the compounds identified, biological response modifiers (e.g., interferon, BCG (BCG), monoclonal antibodies, interleukin 2, Granulocyte Colony Stimulating Factor (GCSF), etc.), PGDF receptor antagonists, herceptins, asparagmase, asparaginase, platinum carmustine, cisplatin, Chlorambucil, cytarabine, dacarbazine, etoposide, flecarbazine (flucarbazine), fluorouracil, gemcitabine, hydroxyurea, ifosfamide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, thioguanine, thiotepa, topotecan, busulfan, vinblastine, vincristine, mitoxantrone, oxaliplatin, procarbazine, griseofulvin, taxol or taxol, taxotere, azathioprine, docetaxel analogs/homologs, derivatives of these compounds, and combinations thereof.

Examples of decongestants that may be used in the devices and methods described herein include, without limitation, epinephrine, pseudoephedrine, oxymetazoline, phenylephrine, tetrahydrozoline, and xylometazoline. Examples of mucolytic agents that may be used in the devices and methods described herein include, without limitation, acetylcysteine, alpha streptococci, and guaifenesin. Antihistamines such as azelastine, diphenhydramine, and loratadine can also be used in the methods and devices described herein.

Suitable high permeability agents that may be used in the devices described herein include, without limitation, furosemide, sodium chloride gel, and other salt formulations that absorb water from tissue or substances that directly or indirectly alter the permeability of the mucosal layer.

Other bioactive agents useful in the present invention include, without limitation, free radical scavengers; a nitric oxide donor; rapamycin; methyl rapamycin; everolimus; tacrolimus; 40-O- (3-hydroxy) propyl-rapamycin; 40-O- [2- (2-hydroxy) ethoxy ] ethyl-rapamycin; rapamycin analogs containing tetrazole, such as those described in U.S. Pat. No. 6,329,386; estradiol; clobetasol; an idoxifen; tazarotene; an alpha-interferon; host cells, including but not limited to prokaryotic and eukaryotic cells, such as epithelial cells and genetically engineered epithelial cells; dexamethasone; and any prodrugs, metabolites, analogs, homologs, derivatives, salts, and combinations thereof.

Examples of free radical scavengers include, without limitation, 2 ', 6, 6' -tetramethyl-1-piperidinyloxy, free radical (TEMPO); 4-amino-2, 2 ', 6, 6' -tetramethyl-1-piperidinyloxy, free radical (4-amino-TEMPO); 4-hydroxy-2, 2 ', 6, 6' -tetramethyl-piperidin-1-oxyl, free radical (TEMPOL), 2, 2 ', 3, 4, 5, 5' -hexamethyl-3 imidazoline-methyl 1-yloxysulphate, free radical; 16-doxyl-stearic acid, free radical; superoxide dismutase mimics (SODm) and any analogs, homologs, derivatives, salts, and combinations thereof. The nitric oxide donor includes, but is not limited to, S-nitrosothiol, nitrite, N-oxo-N-nitrosamine, substrate for nitric oxide synthase, diazeneDialdehydes (e.g. spermine diazenes)A dialdehydes), and any analogs, homologs, derivatives, salts, and combinations thereof.

Material

The devices described herein may be made of any suitable material or combination of materials. In certain aspects, one or more of the materials may be biodegradable, bioerodible, or otherwise erodable. In these approaches, the rate of biodegradation of the degradable portion of the device can be affected by a number of factors including, without limitation, the type of material used to form the portion, the size and shape of the device, and the environment of use. The devices described herein may be made from a single material, or may be made from a combination of materials.

One or more portions of the device may comprise one or more polymers. The polymer may be biodegradable, but is not required. Examples of biodegradable polymers that may be suitable for use in the methods and devices described herein include, without limitation, alginate, cellulose and esters, dextran, elastin, fibrin, hyaluronic acid, polyacetal, polyarylate (L-tyrosine derived or free acid), poly (alpha-hydroxy-ester), poly (beta-hydroxy-ester), polyamide, poly (amino acid), polyalkanoate, polyalkylene alkylate, polyalkylene beta-orcinol methyl ester (oxylate), polyalkylene succinate, polyanhydride, polyaspartic acid (aspartic acid), polybutylene diglycolate, poly (caprolactone)/poly (ethylene glycol) copolymer, poly (carbonate), L-tyrosine derived polycarbonate, polynitrile acrylate, Polydihydropyrans, poly (dioxanones), poly-p-dioxanones, poly (e-caprolactone), poly (e-caprolactone-dimethyltrimethylene carbonate), poly (esteramides), poly (esters), aliphatic polyesters, poly (ether esters), poly (ethylene glycol)/poly (orthoester) copolymers, poly (glutaric acid), poly (glycolic acid), poly (glycolide)/poly (ethylene glycol) copolymers, poly (glycolide-trimethylene carbonate), poly (hydroxyalkanoates), poly (hydroxybutyrate-co-valerate), poly (iminocarbonates), polyketals, poly (lactic acid), poly (lactic acid-co-glycolic acid)/poly (ethylene glycol) copolymers, poly (lactic acid-co-glycolic acid)/poly (ethylene glycol) copolymers, poly (ethylene glycol), poly (lactide), poly (lactide-co-caprolactone), poly (DL-lactide-co-glycolide), poly (lactide-co-glycolide)/poly (ethylene glycol) copolymers, poly (lactide)/poly (glycolide) copolymers, polyorthoesters, poly (oxyethylene)/poly (oxypropylene) copolymers, polypeptides, polyphosphazenes, polyphosphates, polyphosphate urethanes, poly (trimethylene fumarate-co-ethylene glycol), poly (trimethylene carbonate), poly (tyrosine carbonate), polyurethanes, PorLastin or silk-elastin (silk-elastin) polymers, spider silk, tepaflex, terpolymers (copolymers of glycolide, lactide or dimethyltrimethylene carbonate), and combinations thereof, A mixture or a copolymer. Examples of non-biodegradable polymers suitable for use in the methods and devices described herein include, without limitation, poly (ethylene vinyl acetate), poly (vinyl acetate), silicone polymers, polyurethanes, polysaccharides (e.g., cellulosic polymers and cellulosic derivatives, acyl substituted cellulose acetate and derivatives thereof), copolymers of poly (ethylene glycol) and poly (butylene terephthalate), polystyrene, polyvinyl chloride, polyvinyl fluoride, poly (vinylimidazole), chlorosulfonated polyolefins, polyethylene oxide, and copolymers and mixtures thereof.

In other aspects, one or more portions of the device comprise one or more metals, metallic materials, or metal alloys. Examples of suitable metals include, without limitation, zinc, magnesium, cobalt, chromium, nickel, platinum, stainless steel, titanium, tantalum, and iron, combinations thereof, and the like. Examples of suitable metal alloys include, without limitation, magnesium, nickel-cobalt alloys, nickel-titanium alloys, copper-aluminum-nickel alloys, copper-zinc-aluminum-nickel alloys, combinations thereof, and the like. In other aspects, one or more portions of the device may comprise an elastic material.

In certain aspects, one or more portions of the device can comprise one or more hemostatic substances, which can be a drugMay help to stop or prevent bleeding. For example, the devices described herein can comprise oxidized cellulose (e.g., cellulose acetate)SURGICEL ) Gelatin sponges (e.g. sponge)) Microfibrillar collagen (e.g. collagen)) One or more sealants or adhesives (as described in more detail below), combinations thereof, and the like.

In certain aspects, one or more portions of the device comprise mucoadhesive or other adhesive material. For example, certain devices comprise one or more mucoadhesive hydrogels, such as PLG polymers, polyacrylic acid, carageenan, alginates, xanthan gum, carboxymethyl cellulose, hydroxypropyl cellulose, chitin, chitosan, hyaluronic acid, plant lectins, derivatives thereof, combinations thereof, and the like. In other embodiments, the device may comprise fibrin glue, cyanoacrylate glue, combinations thereof, and the like. When the device comprises fibrin glue, the glue may be formed by mixing fibrinogen and thrombin. The fibrin glue may further comprise one or more coagulation factors or other components of the coagulation cascade (e.g. vitamin K, calcium, phospholipids, etc.), which may affect the strength or durability of the resulting polymerized fibrin. The fibrin glue may further comprise one or more anti-fibrinolytic agents (e.g., apolipoproteins) that may affect the rate of degradation/fibrinolysis of the clot. These adhesive materials may additionally be designed to release one or more drugs therefrom.

Method of producing a composite material

Methods of treating tonsil tissue are also described. In general, the methods described herein involve implanting or delivering one or more of the above-described devices to one or more regions of tonsil tissue. For example, in some methods, one or more tissue-piercing devices may be at least partially implanted into tonsil tissue. In other methods, one or more clips or tissue fixation devices may be anchored or attached to the tissue. In other methods, multiple space-filling implants may be delivered into or around tonsillar tissue. In other methods, one or more gels, foams, patches, meshes, films or sheets may be implanted, attached or delivered to tonsil tissue. In other versions, a combination of the above devices may be delivered to tonsil tissue. Any of these devices may be administered or implanted into any suitable region of tonsillar tissue. In certain methods, one or more devices are applied to a tonsil, adenoid, lingual tonsil, or eustachian tube tonsil. In other methods, one or more devices are applied to one or more portions of the tonsillar fossa, such as the palatopharyngeal arch, palatoglossal arch and superior constrictor muscles, or other connective or peripheral tissues.

When one or more devices as used herein are delivered to tonsil tissue, the devices may be delivered to any suitable tissue at any suitable time. In certain methods, one or more devices are delivered to a swollen or infected area of tonsil tissue. In certain methods, the device may provide one or more functions useful for tonsillar procedures (e.g., tonsillectomy) (e.g., reduction of swelling). Indeed, in certain aspects, the devices described herein may be used to treat one or more conditions or symptoms associated with, for example, tonsillitis, obstructive sleep apnea, and the like. In other methods, one or more devices are delivered to tonsil tissue during a tonsil procedure. For example, during a tonsillectomy, one or more devices may be delivered to the exposed tonsillar bed after removal of at least a portion of the palatal tonsils. In some cases, one or more devices may function to cover or seal the exposed tonsil bed from external forces or stimuli. In other methods, one or more devices are delivered to tonsil tissue after a tonsil procedure. This may be useful for continued treatment of post-operative discomfort following tonsil procedures. For example, if the patient is experiencing discomfort 1 week after a tonsillar surgical procedure, one or more devices may be delivered to the tonsillar tissue to provide one or more analgesics. It should be appreciated that the devices may be delivered to the tonsil tissue at any combination of the above points in time (e.g., one or more devices delivered prior to a tonsil procedure, one or more devices delivered during a tonsil procedure, one or more devices delivered after a tonsil procedure, etc.). It should also be understood that one or more adhesives (e.g., fibrin glue) may be used to cover or encapsulate portions of one or more of the devices described herein, or may be used to help secure one or more devices to tissue. These binders may further be used to release one or more drugs.

In general, the devices described above may be designed to deliver one or more drugs to tonsil tissue. In certain aspects, the one or more drugs may treat inflammation or swelling of one or more tonsil tissues. In other aspects, one or more drugs may aid in post-operative recovery after tonsil procedures. More particularly, the methods may comprise administering one or more antibiotics, analgesics, hemostatic agents, healing-promoting agents, or combinations thereof. As noted above, the device may be administered before, during, or after a tonsillectomy, adenoidectomy, tonsillectomy, or any other tonsillar procedure.

As described above, certain methods include implanting one or more tissue-piercing devices at least partially into tonsil tissue. Any number of tissue-piercing devices may be implanted in the tissue, and each tissue-piercing device may have any suitable configuration of elements as described above. When multiple tissue-piercing devices are implanted in tonsillar tissue, the tissue-piercing devices may have the same configuration, or may have different configurations. When the tissue-piercing device is used to release one or more drugs over a period of time, the tissue-piercing device may release the same drug over the same period of time, or may deliver different drugs over different periods of time. For example, some tissue-piercing devices may be designed to deliver antibiotics over a period of time (e.g., 3 days), while other tissue-piercing devices may be designed to deliver one or more analgesics or local anesthetics over a second period of time (e.g., 10 days). This potential variation in configuration between different tissue-piercing devices, as well as the variation in drug delivery of other devices described herein, may give the physician considerable leeway in designing treatment regimens for individual patients.

The tissue-piercing device may be implanted in the tissue in any suitable manner. The tissue-piercing devices may be implanted simultaneously or sequentially. In some versions, one batch of tissue-piercing devices is implanted simultaneously, but different batches are implanted sequentially. In some methods, one or more tissue-piercing devices may be introduced through the catheter with the aid of a pusher. In other methods, the tissue-piercing device is released from one or more spray guns or injection devices. In other methods, a plurality of tissue piercing devices may be released from the base. The base may be any suitable structure capable of removably receiving one or more tissue-piercing devices. The base may have any suitable size or shape and may be capable of receiving any number of tissue piercing devices. For example, fig. 21A illustrates a block-shaped base (2100) designed to receive 3 wires (2102), while fig. 21B illustrates a cylindrical base (2104) designed to receive 5 wires (2106).

The base may removably receive at least a portion of one or more delivery devices. Fig. 22A illustrates a suitable version of a delivery device (2200). There is shown a handle (2202) and a shaft (2204) connected to a base (2206) housing a plurality of tissue piercing devices (2208). Although shown as straight, the rod (2204) may have one or more curved or angled portions. Fig. 22B illustrates one such version of a delivery device (2210) comprising a handle (2212) and a rod (2214). Also shown is a base (2216) and a tissue-piercing device (2218). Although shown in fig. 22B as having one angled portion (2220), rod (2214) may have any suitable number of angled or curved portions.

Fig. 23A-23C illustrate one method of applying a plurality of tissue piercing devices (2300) to tonsillar tissue (2302) from a base (2304). Base (2304) may be attached to any suitable delivery device, such as those just described above. First, the base (2304) and tissue-piercing device (2300) are pushed to the tonsil tissue, as shown in fig. 23A. The base (2304) may then be further advanced so as to advance one or more tissue-piercing devices (2300) into tonsil tissue (2302), as shown in fig. 23B. The tissue-piercing device (2300) may then be disengaged from base (2304) such that the tissue-piercing device is at least partially implanted in tonsil tissue (2302), as shown in fig. 23C. The tissue-piercing device (2300) may be disengaged from the base (2304) in any suitable manner. In certain aspects, the delivery device (not shown) may comprise one or more pushers (not shown) that disengage the tissue-piercing device (2300) from the base (2304). In other versions, the tissue-piercing device may be designed to remain within the tissue, as described in more detail above. Once the tissue-piercing device (2300) is inserted into the tonsil tissue (2302), the tissue-piercing device (2300) may be prevented from being pulled out of the tonsil tissue (2302). Thus, when base (2304) is withdrawn from tonsil tissue (2302), tissue-piercing device (2300) may remain in place such that it is disengaged from base (2304).

Fig. 24A-24C illustrate another method by which a plurality of tissue-piercing devices (2400) may be implanted into tonsillar tissue (not shown). Fig. 24A shows a perspective view of a ring (2402) containing holes (2404). Also shown is a tissue-piercing device (2400) disposed at least partially in the aperture (2404). Generally, each tissue-piercing device (2400) can be designed to slide or move through the aperture (2404) of the loop (2402). To implant tissue-piercing device (2400) into tonsillar tissue, tissue-piercing device (2400) and loop (2402) may first be placed in an "open" configuration, with a substantial portion of each tissue-piercing implant (2400) remaining outside of loop (2402), as shown in the top view shown in fig. 24B. The ring (2402) may then be placed around a portion of tonsil tissue, and the tissue-piercing implant (2400) may be moved into a "closed" configuration in which a majority of each tissue-piercing device (2400) has been pushed through the hole (2404) into the ring (2402), as shown in fig. 24C. Moving the tissue-piercing device (2400) through the aperture (2404) can cause the tissue-piercing device to penetrate tonsil tissue located within the loop (2402). In certain versions, tissue-piercing device (2400) may be passed completely through aperture (2404) such that loop (2402) may be removed while retaining tissue-piercing device (2400) implanted in the tissue. In other versions, one or more tissue-piercing devices (2400) remain coupled to the loop (2402) such that the loop (2402) remains in place against the tissue.

Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be obvious that certain changes and modifications may be practiced, and are within the scope of the appended claims.

Claims

1. A system for treating tonsil tissue, the system comprising:

a delivery device comprising a handle, a base, and a rod connecting the handle and the base; and

a plurality of tissue-piercing filaments partially and releasably seated in the base, wherein the plurality of tissue-piercing filaments are at least partially implanted in the tonsil tissue as the base is advanced toward the tonsil tissue.

2. The system of claim 1, wherein the plurality of tissue-piercing filaments comprise one or more drugs delivered to tonsil tissue.

3. The system of claim 2, wherein the one or more drugs comprise one or more anesthetics.

4. The system of claim 2, wherein the one or more drugs comprise one or more antibiotics.

5. The system of claim 1, wherein at least one of the plurality of tissue-piercing filaments comprises a plurality of notches, wherein the plurality of notches inhibit removal of the at least one tissue-piercing filament.

6. The system of claim 5, wherein the plurality of notches are formed by cutting the plurality of notches.

7. The system of claim 1, wherein the plurality of tissue-piercing filaments are biodegradable.

8. The system of claim 1, wherein the rod comprises an angled portion.