| Extracellular matrix based gastroesophageal junction reinforcement device -> Monitor Keywords |
|
|
 
Extracellular matrix based gastroesophageal junction reinforcement deviceRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Extract, Body Fluid, Or Cellular Material Of Undetermined Constitution Derived From Animal Is Active Ingredient, Digestive System (e.g., Salivary Gland, Etc.), Gastrointestinal System (e.g., Intestine, Stomach, Gall Bladder, Etc.)Extracellular matrix based gastroesophageal junction reinforcement device description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070166396, Extracellular matrix based gastroesophageal junction reinforcement device. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Patent Application No. 60/757,086, filed on Jan. 6, 2006, and which is incorporated herein by reference in its entirety. [0003] Described herein are medical devices for implantation in patients that may be used to connect an esophagus or portions thereof with a stomach to form and/or repair a gastro-esophageal junction. Methods of use of the medical device are also described herein. [0004] Surgical procedures involving the esophagus have always been challenged by their high morbidity and mortality rates (Orringer and Stirling, 1988, J Thorac Cardiovasc Surg. 96:887-93; Heitmiller et al., 1999, Dis Esophagus. 12:264-9; Whyte and Orringer, 1994, Semin Radiat Oncol. 4:146-156). Radical esophagectomy, the therapy of choice for patients with esophageal cancer or patients with high grade dysplasia, is usually followed by a complex reconstructive surgery to restore food transit. The most commonly accepted approach has been mobilizing the stomach through the mediastinum after shaping it into a tube and anastomosing it to the remaining cervical esophagus ("gastric pull-up")(Orringer et al., 2001, World J Surg. 25:196-203). When the stomach is not available, other options such as colonic or small bowel interposition are utilized (Yildirim, 2004, J Gastrointest Surg. 8:675-8). Although partially successful, the outcome of these procedures remains suboptimal due to the high associated morbidity (lannettoni et al., 1995, J Thorac Cardiovasc Surg. 110:1493-500). The mobilization of the abdominal organs into the mediastinal cavity usually yields to extensive compromise of the blood supply and the resulting poorly vascularized tissue has a reduced healing capacity that contributes to complications at the anastomotic site (Reavis et al., 2005, Ann Surg. 241:736-45). Anastomotic leakage is the most common complication associated with high morbidity and it is considered an independent risk factor in the prognostic outcome (Rizk et al., 2004, J Am Coll Surg. 198:42-50). For many years, surgeons have attempted modifications of the surgical technique to improve this condition with limited success. In fact, controversy still exists on whether a complete mechanical anastomosis significantly decreases the leak rate when compared to a hand sewn anastomosis. Another common complication related to poor healing capacity and scarring is the post-operative stricture of the anastomosis that requires endoscopic dilation in up to 50% of patients (Orringer et al., 2001, World J Surg. 25:196-203). On the other hand, partial resection of the esophagus (i.e. mucosectomy in Barret's disease) is limited by the inability of the tissue to regenerate in an organized manner and leads to scar tissue formation and ultimately esophageal stenosis (Stein et al., 2000, Ann Surg. 232:733-42; DeMeester and DeMeester, 1999, Adv Surg. 33:29-68). [0005] There exists a need for anastomotic reinforcement in connection with surgical procedures involving the esophagus. Recently, regenerative medicine approaches have shown promising results using extracellular matrix (ECM) scaffolds derived from the small intestinal submucosa (SIS) and urinary bladder (UBM) in the attempt to reconstitute normal tissue. Several pre-clinical and clinical applications have been reported for numerous body structures including vascular, skin, musculo-skeletal, lower urinary tract, and esophageal tissue. SUMMARY [0006] ECM scaffolds are provided as anastomotic reinforcement devices and to reduce scarring and inflammation to better promote healing with decreased complications. Thus provided, according to one embodiment of the medical devices described herein, are medical devices for implantation in patients having lost at least part of their esophagus or having damage to their esophagus. According to one embodiment, the medical devices described herein connect the esophagus or remaining part of the esophagus with the stomach to form a gastro-esophageal junction that promotes healing and encourages new host tissue growth, diminishes scar tissue formation and stricture while distributing the load, decreasing tension, and increasing vascular perfusion at the anastomotic site. The medical device comprises extracellular matrix (ECM) shaped into a conformation that more closely approximates the geometry of the native gastro-esophageal junction than does direct attachment of the remaining stomach, often tubularized, to the shortened esophagus. Methods of use of the medical device are also encompassed by the present invention. [0007] In one embodiment, a device is provided comprising one or more layers of extracellular matrix tissue, for example and without limitation 2-10 layers, and comprising a tubular esophageal portion having essentially a constant diameter (the diameter can increase, decrease or vary so long as it substantially conforms with a shape of a portion of an esophagus); and a tubular gastric portion attached to the esophageal portion at a junction having a diameter that increases from the junction to a distal tip of the gastric portion. The diameter of the gastric portion may increases in an essentially uniform manner from the junction to the distal tip of the gastric portion. Typically, the gastric portion is modeled to conform with a portion of a patient's stomach to which a remaining portion of the patient's esophagus is to be attached, and in one embodiment, the gastric portion is modeled to conform with a cardiac region of a stomach adjacent to a cardiac opening of the stomach. [0008] In certain embodiments, the esophageal portion has a length of between 1 to 30 cm and a diameter of between 0.5 to 5 cm; and/or the gastric portion has a length of between 1 to 8 cm and the distal tip of the gastric portion has a diameter of between 1-12 cm. According to other embodiments, the esophageal portion has a length of about 3 cm and a diameter of about 2.3 cm; and/or the gastric portion has a length of about 3-4 cm and a diameter of the distal tip of about 7 cm. [0009] The extracellular matrix tissue may be isolated by any useful method from any useful source. In one example, the tissue is isolated from urinary bladder tissue, for example and without limitation porcine urinary bladder tissue. The extracellular matrix tissue may comprise epithelial basement membrane and subjacent tunica propria. The extracellular matrix tissue may comprise tunica submucosa. The extracellular matrix tissue may comprise epithelial basement membrane, subjacent tunica propria, tunica submucosa and/or tunic muscularis. The extracellular matrix tissue also may be isolated from intestinal submucosa, esophagus or dermis of skin. The device may be seeded with cells, typically human cells, such as a patient's cells into whom the device is to be implanted or allogeneic cells. The cells may be implanted in the device prior to surgery and may be allowed to populate the device prior to surgery by incubation in a bioreactor. Alternately, autologous or allogeneic cells may be implanted at the time of surgery, for example and without limitation, by sattaching a suitable piece of tissue to the device during implantation surgery. [0010] Also provided is a mold for molding extracellular matrix tissue into a device as described herein, comprising a tubular esophageal portion having essentially a constant diameter (the diameter can increase, decrease or vary so long as it substantially conforms with a shape of a portion of an esophagus), and a tubular gastric portion attached to the esophageal portion at a junction, the gastric portion having a diameter that increases from the junction to a distal tip of the gastric portion. As with the device described herein, the diameter of the gastric portion of the mold may increase in an essentially uniform manner from the point of connection to the esophageal portion to the distal tip of the gastric portion. In other embodiments, the esophageal portion of the mold has a length of between 1 to 30 cm and a diameter of between 0.5 to 5 cm; and the gastric portion has a length of between 1 to 8 cm and the distal tip of the gastric portion has a diameter of between 1-12 cm. In further embodiments, the esophageal portion has a length of about 3 cm and a diameter of about 2.3 cm; and the gastric portion has a length of about 3-4 cm and a diameter of the distal tip of about 7 cm. The mold may be made of one or more water-permeable materials. In certain embodiments, the gastric portion is modeled to conform with a portion of a stomach, for example and without limitation, the gastric portion is modeled to conform with a cardiac region of a stomach adjacent to a cardiac opening of the stomach. Due to variations in esophageal and gastric geometry prior to and after surgery, the esophageal portion of the mold may be detachable from the gastric portion to allow interchangeability of different-shaped gastric portions. Further, the mold may be collapsible by any means known in the art to facilitate removal of the device from the mold. [0011] In another embodiment of the technology described herein, a method is provided of reinforcing an anastomotic site in a patient comprising implanting a device between a portion of (e.g., that portion remaining after surgery) the patient's esophagus and stomach, the device can be any device comprising one or more layers of extracellular matrix tissue and comprising a tubular esophageal portion having essentially a constant diameter; and a tubular gastric portion attached to the esophageal portion at a junction having a diameter that increases from the junction to a distal tip of the gastric portion and variations thereof described herein. In certain embodiments, the patient has or previously has had Barrett's disease, esophageal cancer, congenital atresia, or trauma to the esophagus. BRIEF DESCRIPTION OF THE DRAWINGS [0012] FIG. 1 is a schematic of a cross-sectional view of the wall of the urinary bladder (not drawn to scale). The following structures are shown: epithelial cell layer (A), basement membrane (B), tunica propria (C), muscularis mucosa (D), tunica submucosa (E), tunica muscularis extema (F), tunica serosa (G), tunica mucosa (H), and the lumen of the bladder (L). [0013] FIGS. 2A-2C show schematically two embodiments of an extracellular matrix device described herein. FIG. 2A provides two views of a first embodiment and FIG. 2C provides a single view of a second embodiment as described herein. The esophageal and gastric portions of the device are indicated as well as the proximal and distal tips of the device. [0014] FIGS. 3A-3D schematically show implantation of one embodiment of a device described herein in a cervical esophageal anastomosis. [0015] FIGS. 4A-4C show implantation of one embodiment of a device described herein in a gastro-espohageal junction anastomosis. DETAILED DESCRIPTION [0016] The present invention is related to a medical device to be implanted in patients having suffered the loss of or damage to at least part of their esophagus. The device comprises one or more layers of extracellular matrix (ECM) molded into a particular shape that more closely approximates the geometry of the native gastro-esophageal junction than does direct attachment of the remaining stomach to the shortened esophagus. In one embodiment, the ECM is molded into a shape that essentially recapitulates the native geometry of the gastro-esophageal junction (the portions of the stomach and esophagus adjacent to the cardiac orifice) prior to tissue loss. The device serves as an inductive support scaffold that facilitates constructive remodeling of this site following segmental esophagectomy. [0017] As used herein, the terms "extracellular matrix" and "ECM" refer to a complex mixture of structural and functional biomolecules including, but not limited to, structural proteins, specialized proteins, proteoglycans, glycosaminoglycans, and growth factors that surround and support cells within mammalian tissues. [0018] Any type of extracellular matrix tissue can be used to make a device as described herein (see generally, U.S. Pat. Nos. 4,902,508; 4,956,178; 5,281,422; 5,352,463; 5,372,821; 5,554,389; 5,573,784; 5,645,860; 5,771,969; 5,753,267; 5,762,966; 5,866,414; 6,099,567; 6,485,723; 6,576,265; 6,579,538; 6,696,270; 6,783,776; 6,793,939; 6,849,273; 6,852,339; 6,861,074; 6,887,495; 6,890,562; 6,890,563; 6,890,564; and 6,893,666). In certain embodiments, the ECM is isolated from a vertebrate animal, for example and without limitation, from a warm blooded mammalian vertebrate animal including, but not limited to, human, monkey, pig, cow and sheep. The ECM can be derived from any organ or tissue, including without limitation, urinary bladder, intestine, liver, esophagus and dermis. In one embodiment, the ECM is isolated from a urinary bladder. The ECM may or may not include the basement membrane portion of the ECM. In certain embodiments, the ECM includes at least a portion of the basement membrane. The material used to make the ECM Device may comprise primarily (that is, greater than 70%, 80%, or 90%) ECM. This material may or may not retain some of the cellular elements that comprised the original tissue such as capillary endothelial cells or fibrocytes. [0019] In one embodiment, the ECM is harvested from porcine urinary bladders. Briefly, the ECM is prepared by removing the urinary bladder tissue from a pig and trimming residual external connective tissues, including adipose tissue. All residual urine is removed by repeated washes with tap water. The tissue is delaminated by first soaking the tissue in a de-epithelializing solution such as hypertonic saline, for example and without limitation, 1.0 N saline, for periods of time ranging from 10 minutes to 4 hours. Exposure to hypertonic saline solution effectively removes the epithelial cells from the underlying basement membrane. The tissue remaining after the initial delamination procedure includes epithelial basement membrane and the tissue layers abluminal to the epithelial basement membrane. This tissue is next subjected to further treatment to remove the majority of abluminal tissues but not the epithelial basement membrane. The outer serosal, adventitial, smooth muscle tissues, tunica submucosa and most of the muscularis mucosa are removed from the remaining de-epithelialized tissue by mechanical abrasion or by a combination of enzymatic treatment, hydration, and abrasion. Mechanical removal of these tissues is accomplished by removal of mesenteric tissues with, for example, Adson-Brown forceps and Metzenbaum scissors and wiping away the tunica muscularis and tunica submucosa using a longitudinal wiping motion with a scalpel handle or other rigid object wrapped in moistened gauze. After these tissues are removed, the resulting ECM consists mainly of epithelial basement membrane and subjacent tunica propria (layers B and C of FIG. 1). [0020] In another embodiment, the ECM is prepared by abrading porcine bladder tissue to remove the outer layers including both the tunica serosa and the tunica muscularis (layers G and F in FIG. 1) using a longitudinal wiping motion with a scalpel handle and moistened gauze. Following eversion of the tissue segment, the luminal portion of the tunica mucosa (layer H in FIG. 1) is delaminated from the underlying tissue using the same wiping motion. Care is taken to prevent perforation of the submucosa (layer E of FIG. 1). After these tissues are removed, the resulting ECM consists mainly of the tunica submucosa (layer E of FIG. 1). [0021] The ECM can be sterilized, and typically decellularized by any of a number of standard methods without loss of its ability to induce endogenous tissue growth. For example, the material can be sterilized by propylene oxide or ethylene oxide treatment, gamma irradiation treatment (0.05 to 4 mRad), gas plasma sterilization, peracetic acid sterilization, or electron beam treatment. The material can also be sterilized by treatment with glutaraldehyde, which causes cross linking of the protein material, but this treatment substantially alters the material such that it is slowly resorbed or not resorbed at all and incites a different type of host remodeling which more closely resembles scar tissue formation or encapsulation rather than constructive remodeling. Cross-linking of the protein material can also be induced by physical and/or chemical methods, including without limitation, treatment with carbodiimide or dehydrothermal or photooxidation methods. More typically, ECM is disinfected by immersion in 0.1% (v/v) peracetic acid (.sigma.), 4% (v/v) ethanol, and 96% (v/v) sterile water for 2 h. The ECM material is then washed twice for 15 min with PBS (pH=7.4) and twice for 15 min with deionized water. Continue reading about Extracellular matrix based gastroesophageal junction reinforcement device... Full patent description for Extracellular matrix based gastroesophageal junction reinforcement device Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Extracellular matrix based gastroesophageal junction reinforcement device patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Extracellular matrix based gastroesophageal junction reinforcement device or other areas of interest. ### Previous Patent Application: Method for manufacturing biomedical bone material with concrete characteristic Next Patent Application: Medical graft products with differing regions and methods and systems for producing the same Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Extracellular matrix based gastroesophageal junction reinforcement device patent info. IP-related news and info Results in 0.16639 seconds Other interesting Feshpatents.com categories: Electronics: Semiconductor , Audio , Illumination , Connectors , Crypto , 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
