Patent Publication Number: US-2011066141-A1

Title: Implantable medical device having an anti-gastric distress agent

Description:
BACKGROUND 
     The described embodiments generally relate to medical devices suitable for at least partial implantation into a body. More particularly, they relate to medical devices having at least an anti-gastric distress agent, and methods of use thereof. 
     Patients for whom normal ingestion of food becomes difficult or impossible may require placement of a feeding tube to assist in providing their nutritional needs. For some individuals, such as comatose patients, stroke victims, or those with a compromised gastrointestinal tract, this may require placement of a feeding tube that is introduced into the stomach for delivery of nutritional products into the stomach. The nutritional products are delivered to the interior of the stomach through the distal end of the feeding tube and/or through side ports along the length of the tube. 
     Feeding tubes inserted percutaneously through a hole in the abdominal and stomach wall, or gastrostomy, are generally referred to as gastrostomy tubes, or “G”-tubes. In some patients, feeding may be accomplished by inserting a tube, referred to as a jejunostomy tube, or “J”-tube or “GJ”-tube, that extends on through the stomach and directly into the jejunum (the middle section of the small intestine). In many cases, a J-tube may be inserted into the jejunum through the interior of a G-tube that has been previously positioned in the stomach, e.g., via the Seldinger percutaneous entry technique. Feeding tubes may also be inserted into the patient&#39;s nose, through the nasal passage, down the esophagus and into the stomach or the small intestines. Collectively, these types of feeding tubes are called nasogastric tubes, or “NG”-tubes. Although its delivery is relatively noninvasive, NG-tubes may contribute to local irritation or infection in the patient&#39;s nasal passage. 
     While indwelling feeding tubes provide several advantages, they also present opportunities for infection. Indwelling feeding tubes are particularly susceptible to infection due to their long term presence in the body. In essence, the feeding tube provides a path from the external environment into the body along which microorganisms can colonize, and eventually produce an infection. Successful colonization along the surface of feeding tubes can even form biofilm layers along its surface. Leakage of gastric contents out of the stomach and into the surrounding skin may also result in inflammation, ulceration, and infection. Gastric contents can include a mixture of nutritional products, dissolved or suspended medications, and gastric secretions. One way to control infection is to clean the feeding tubes periodically by flushing with suitable fluids. Another way is to clean the surrounding skin and to keep it dry. 
     For patients having feeding tubes and abnormally high leakage of gastric contents, gastroesophageal reflux disease (GERD) or acid reflux, peptic ulcers, gastritis, or excess stomach gas, treatment may be difficult. The oral administration or consumption of antacids to treat excess gastric acid and relieve its associated discomfort is well known. 
     Although the active ingredients of commercially available, over-the-counter antacid compositions vary, many of these antacids include alkaline earth (e.g., calcium and magnesium) carbonates and hydroxides. More specifically, antacids are generally available in tablet form or liquid form to neutralize acids in the gastrointestinal tract. Antacids are generally insoluble inorganic salts such as calcium hydroxide, aluminum hydroxide, magnesium hydroxide (MILK of MAGNESIA®), combination of aluminum hydroxide and magnesium hydroxide (MMLOX® or MYLANTA®), calcium carbonate (TUMS® or ROLAIDS®), magnesium carbonate, or sodium bicarbonate (ALKA-SELTZER®). Other antacids include bismuth subsalicylate (PEPTO-BISMOL®) and magaldrate with simethicone. 
     Oral administration or consumption of gastric acid blockers aid to block the release of acid into the patient&#39;s gastrointestinal tract is also known. Histamine 2 receptor antagonists (H2 blockers) are compounds that block the H2 receptors on parietal cells in the stomach that stimulate the secretion of acid by the stomach. Gastric acid blockers, which may also include antacids, include for example cimetidine (TAGAMET®), ranitidine (ZANTAC®), or famotidine (PEPCID AC®), just to name a few. Another class of medication used for gastric acid control is proton pump inhibitors. Proton pump inhibitors act to block the molecular pump that produces acid in the patient&#39;s gastrointestinal tract. Proton pump inhibitors can include for example omeprazole (PRILOSEC®), dexlansoprazole (KAPIDEX®), or esomeprazole (NEXIUM®), just to name a few. 
     Instead of periodic oral administration of some form of infection regulation and/or acid regulation or regular cleaning, it would be desirable to provide a medical device in a patient&#39;s gastrointestinal system, which is designed to prevent infection and/or to relieve or prevent gastric distress or other effects of gastric acid that cause discomfort to the patient. 
     SUMMARY 
     Medical devices suitable for at least partial implantation into a body, and more particularly, having at least one anti-gastric distress agent for partial or full implantation within the gastrointestinal system are provided. Nonlimiting examples of medical devices can include tubes for delivering nutritional products directly into the gastrointestinal system, such as G-tubes or GI-tubes, GJ-tubes, NG-tubes, etc., tubes for delivering other fluid-like materials such as therapeutic agents or drugs, contrast materials or saline, tubes for delivering specified materials to target sites in other body canals, and/or tubes for drainage of fluid or contents. A portion of the medical device further includes at least one anti-gastric distress agent, such as antacids and acid inhibitors (including H2 blockers and proton pump inhibitors), or any combination thereof. The anti-gastric distress agent can promote relief and/or prevent gastric acid buildup, which causes discomfort to the patient, without the hassles of oral administration of such drugs which for some patients is not possible. 
     In one embodiment, the medical device can include a body having a distal end, a proximal end, and a lumen extending therebetween. The device can further include a first section proximate the distal end of the main body and having a first therapeutic agent comprising at least one anti-gastric distress agent. The body preferably has a length such that when the device is at least partially implanted the first section is accessible to the gastrointestinal portion of the patient&#39;s body. 
     In another embodiment, the medical device can further include a second section proximate the proximal end and having an antimicrobial agent. At least a portion of the second section preferably is disposed adjacent to body tissue outside the stomach of the patient. For example, the second section can be placed adjacent the nasal passage or throat of a patient for a NG-tube, or adjacent the gastrostomy wall for a G-tube. In other embodiments, the medical device can include a bolster system configured to anchor the medical device to the body. The bolster system preferably has a sleeve sized to fit within the gastronomy and receive the device body. The sleeve, instead of or in addition to the second section, can have a section including the antimicrobial agent. At least a portion of the sleeve section is disposed adjacent the gastronomy wall of the patient. 
     In another embodiment, the medical device can further include a second anti-gastric distress agent at the first section of the device. The second anti-gastric distress agent preferably has a slower controlled release rate than the first anti-gastric distress agent. In one aspect, the first anti-gastric distress agent is configured to provide immediate relief by absorbing excess gastric acid, while the second anti-gastric distress agent is configured to inhibit the production of gastric acid. The second anti-gastric distress agent can be configured to have a longer release rate or time in order to relieve the adverse effects of gastric acid, such as heartburn. 
     In some embodiments, the first section of the device comprises a first coating and/or a second coating disposed along a portion of at least one of the exterior surface and luminal surface of the medical device&#39;s body. Each of the coatings can include one or more anti-gastric distress agents. Some coatings are biodegradable and are configured to degrade with interaction with the contents of the gastrointestinal tract and/or flushing or feeding. The material of the body may also include and/or be impregnated with one or more anti-gastric distress agents. The device body may further include a second section disposed longitudinally distal to the first section, where the first section of the device includes one or more anti-gastric distress agents and the second section includes one or more anti-gastric distress agents. The cross-sectional area of the second section may be smaller than the first section. 
     In another aspect, methods of treating gastric distress in a gastrointestinal portion of a body of a patient are provided. One embodiment of the medical device can be introduced into said gastrointestinal portion of the body. The medical device may have any combination of one or more therapeutic agents. The medical device may be introduced through a gastronomy formed in the patient and/or through the nasal passage of the patient. Another step includes at least partially implanting the medical device into the gastrointestinal portion of the body such that the first section is accessible to the gastrointestinal portion of the patient&#39;s body. 
     The above, as well as other advantages of the preferred embodiments, will become readily apparent to those skilled in the art from the following detailed description of a preferred embodiment when considered in the light of the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of one embodiment of a medical device. 
         FIGS. 2A-2D  are cross-sectional views taken along line  2 - 2  in  FIG. 1 , depicting various embodiments of the medical device. 
         FIGS. 3A-3D  are cross-sectional views taken along line  3 - 3  in  FIG. 1 , depicting various embodiments of the medical device. 
         FIG. 4  is a schematic illustration of a medical device implanted within the gastrointestinal system of a body. 
         FIG. 5A  is a close-up view of a medical device implanted within the gastrointestinal system of the body of  FIG. 4 . 
         FIG. 5B  is a close-up view of a medical device implanted within the gastrointestinal system of the body of  FIG. 4 . 
         FIG. 6  is perspective view of another embodiment of a medical device. 
     
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting. 
     In the following discussion, the terms “proximal” and “distal” will be used to describe the opposing axial ends of the inventive device, as well as the axial ends of various component features of the device. The term “proximal” is used in its conventional sense to refer to the end of the device (or component thereof) that is closest to the operator during use of the device. The term “distal” is used in its conventional sense to refer to the end of the device (or component thereof) that is initially inserted into the patient. 
     The term “medical device” will be used to describe devices for partial or full implantation within the gastrointestinal system, including but not limited to: tubes for delivering nutritional products directly into the gastrointestinal system, or particularly, the stomach and/or the jejunum of a patient, such as G-tubes or GI-tubes, GJ-tubes, NG-tubes, etc; for delivering other fluid-like materials such as drugs, contrast materials or saline; for delivery of specified materials to target sites in other body canals; and/or for drainage of fluid or contents, for example for drainage of the gastric fluid. 
     The term “anti-gastric distress agent” will be used to describe any or all types of therapeutic agents configured to, at least one of, interact, neutralize, inhibit, reduce, or eliminate gastric hyperacidity or the adverse effects of gastric acid. Specific non-limiting anti-gastric distress agents are described below, including antacids, H2 blockers, and proton pump inhibitors. However, other types of anti-gastric distress agents are known by those skilled in the art are considered within the scope and spirit of the present embodiments. 
     The term “antimicrobial agent” means any agent that has killing or growth inhibiting effects on one or more microorganisms. 
     The term “biodegradable material” refers to a material that dissipates upon implantation within a body, independent of the mechanisms by which dissipation can occur, such as dissolution, degradation, absorption and excretion. The actual choice of which type of materials to use may readily be made by one of ordinary skill in the art. Such materials are often referred to by different terms in the art, such as “bioresorbable,” “bioabsorbable,” or “biodegradable,” depending upon the mechanism by which the material dissipates. The prefix “bio” indicates that the erosion occurs under physiological conditions, as opposed to other erosion processes, caused for example, by high temperature, strong acids or bases, UV light or weather conditions. 
     The term “carrier material” refers to a material that forms a mixture with a therapeutic agent on a surface or in an implantable medical device. The carrier material may control the release of the therapeutic agent from the medical device. 
     The term “barrier layer” is any layer that is placed over at least a portion of a therapeutic agent present in or on an implantable medical device. In general, the therapeutic agent will not be present in the barrier layer. Any mixing of a therapeutic agent with the barrier layer is unintentional and merely incidental. The barrier layer may or may not be the outer-most layer present on the device. For example, a therapeutic agent may be coated onto a surface of a device, a first barrier layer placed over the therapeutic agent and further barrier layers and layers containing the same or a different therapeutic agent placed on the first barrier layer. The barrier layer may control the, release of the therapeutic agent from the medical device upon implantation. 
     The term “controlled release” refers to the release of an agent at a predetermined rate. A controlled release may be constant or vary with time. A controlled release may be characterized by a drug elution profile, which shows the measured rate that the agent is removed from a device in a given solvent environment as a function of time. For example, a controlled release elution profile from a medical device may include an initial burst release associated with the implantation of the medical device, followed by a more gradual subsequent release. A controlled release may be a gradient release in which the concentration of the agent released varies over time or a steady state release in which the agent is released in equal amounts over a certain period of time (with or without an initial burst release). 
     As used herein, the term “therapeutic agent” refers to any pharmaceutically active agent that produces an intended therapeutic effect on the body to treat or prevent conditions or diseases. 
     Now referring to all of the figures where like reference numerals are used throughout all of the figures to refer to generally like components,  FIG. 1  illustrates one embodiment of a medical device  10  having at least one therapeutic agent for partial or full implantation within the body, preferably within the gastrointestinal system. In this embodiment, the medical device  10  comprises a cannula  11  having a main body  12  defining a lumen  14  about a longitudinal axis. The-medical device  10  includes an exterior surface  16  and an interior surface  18 , and a distal end  20  and a proximal end  22 . The length of the cannula  11  extends from the distal end  20  to the proximal end  22 . A first section  24  of the cannula  11  extends along a portion of the length, and a second section  26  extends along another axially distinct portion of the length. Both the first and second sections  24 ,  26  extend at least partially circumferentially around the cannula  11  and at least partially axially along a respective portion of the length. As illustrated in  FIG. 1 , the first section  24  is preferably near the distal end  20  and the second section  26  is preferably near the proximal end  22 . 
     The cross-sectional shape of the medical device can be any shape suitable for the types of procedures in which the device will be utilized. A circular cross-sectional shape is particularly preferable in embodiments in which the device comprises a cannula, such as that illustrated in  FIG. 1 . A circular cross-sectional shape maximizes space within the lumen  14  of the cannula  11  while also providing a suitable shape for interfacing with a body organ or part. Furthermore, the medical device can have any suitable configuration of lumen(s), and the chosen configuration will depend on the application for which the device is used. Single and multi-lumen configurations can be utilized. U.S. Pat. No. 7,306,580, which is hereby incorporated by reference in its entirety, illustrates various suitable cross-sectional shapes and lumen configurations for use in medical devices according to the present invention. 
     The medical device  10  includes at least one of various therapeutic agents for at least relieving and/or preventing at least one of undesirable gastric acid buildup, preventing infection, or any combinations thereof. For example, in the embodiment shown in  FIG. 1 , the medical device includes a first therapeutic agent  28  at the first section  24  of the cannula  11 , and a second therapeutic agent  30  at the second section  26  of the cannula  11 . In other embodiments, the medical device  10  can include more therapeutic agents, for example, a third therapeutic agent  31  as shown in  FIGS. 2B-2D . 
     The therapeutic agents  28 ,  30 ,  31  can be associated with the cannula  11  in a variety of manners described below. Any suitable technique for placing a therapeutic agent in, on, or near a medical device for release from the medical device can be utilized, For example, in the cross-sectional view illustrated in  FIG. 2A , the external surface  16  of the first section  24  of the cannula  11  includes a coating layer  36  comprising a first therapeutic agent  28  posited thereon. A portion  37  of the material of the first section  24  can include the same or another therapeutic agent  31  impregnated within the material. Also, in the cross-sectional view of a preferred embodiment illustrated in  FIG. 3A , the external surface  16  of the second section  26  of the cannula  11  includes a coating layer  38  comprising a second therapeutic agent  30  posited thereon. Other embodiments are described in more detail below. 
     Many alternative embodiments of the orientation and placement of the therapeutic agents are within the scope of the present invention. For example,  FIGS. 2B-2D  illustrate cross-sectional views of alternative embodiments of the first section  24  of the cannula  11 , and  FIGS. 3B-3D  illustrate cross-sectional views of alternative embodiments of the second section  26  of the cannula  11 . 
     In  FIG. 2B , a first coating layer  36 A comprises a first therapeutic agent  28 , represented by the dashed line, and a second, more inner coating layer  36 B comprises another therapeutic agent  31 , each disposed on the exterior surface  16  of the cannula  11 . In  FIG. 2C , a coating layer  34  disposed on the interior surface  18  of the cannula  11  comprises a first therapeutic agent  28  and a portion  37  of the material of the first section  24  comprises another therapeutic agent  31  impregnated therein. In  FIG. 2D , the coating layer  34  disposed on the interior surface  18  of the cannula  11  comprises a first therapeutic agent  28 , and the coating layer  36  disposed on the exterior surface  16  of the cannula  11  comprises another therapeutic agent  31 . In other embodiments, multiple coating layers and impregnated materials can each include a single therapeutic agent. In other embodiments, a coating layer or impregnated material can include a combination of therapeutic agents. 
     Similarly, the second therapeutic agent  30  can be associated with the second section  26  of the cannula  11 . For example, in  FIG. 3B , a portion  42  of the material of the second section  26  of the cannula  11  comprises a second therapeutic agent  30  impregnated therein. In  FIG. 3C , a coating layer  40  disposed along the interior surface  18  of the cannula  11  comprises a second therapeutic agent  30 . In  FIG. 3D , one or more therapeutic agents  30 A,  30 B can be included in two coatings: a coating layer  38  disposed on the exterior surface  16  and a coating layer  40  disposed on the interior surface  18 . In addition to the various arrangements for each of the therapeutic agents, any suitable combination of arrangements may be utilized and/or more than one first, second, third therapeutic agents may be utilized with the medical device. For example, although some of the figures illustrate more than one coating, some embodiment may include only one coating with one therapeutic agent. 
       FIG. 4  schematically illustrates the relative position of at least a partially implanted embodiment of the medical device  10 A and a bolster system  41  when the device is inserted through an opening in the abdominal wall of a patient and into the gastrointestinal system, or more specifically the stomach. The bolster system  41  can include an external bolster member  40  and an internal bolster member  48 . The external bolster member  40  is in cooperating relationship with the medical device  10 A of the type that extends from the exterior of the patient to a site internal of the patient. In the non-limiting example illustrated herein, the medical device  10 A is an enteral feeding tube, such as a gastrostomy tube, or G-tube. As illustrated, the distal end  20  of the medical device  10 A extends through an epidermal surface  42  and other layers of the skin, through subcutaneous layers including an abdominal wall  44  and a stomach wall or lining  46 , and into the stomach. Some main components of the gastrointestinal system are also depicted in the figure including: the fundus of the stomach; the main body, or gastric lumen, of the stomach; the antrum of the stomach which is the portion before the outlet; and the jejunum which is the middle section of the small intestines. 
       FIG. 4  illustrates one embodiment of the external bolster  40 . In the embodiment shown, the external bolster  40  is provided external of the patient for anchoring the medical device  10 A along the patient&#39;s skin. The external bolster  40  includes a base portion  50  that is positioned in a manner to abut, or substantially abut, the external epidermal surface  42 , and an elongated body portion  52  that is configured to receive and surround the medical device  10 A. An optional securing structure, such as twist lock member  54 , may be provided around the elongated body  52  for applying a gripping pressure on the medical device  10 A. Preferably, the base portion  50  comprises the dome-like configuration. Utilizing a dome-like configuration at the distal portion of the base for contacting the skin of the patient provides bolstering with a limited ability to rock back and forth upon movement of the medical device  10 A. Excessive rocking movement can cause trauma to the skin of the patient. 
     The internal bolster member  48  depicted is one example of the type of internal bolster used with tubes. Typically, the internal bolster  48 , such as a balloon or a flared portion of the tube, is provided around a portion of the medical device  10 A. The internal bolster is positioned internal of the stomach to abut and hold the anterior stomach wall  46  against the abdominal wall  44 . The internal and external bolsters  48 ,  40  are configured to maintain the surface  42  of the body and the internal surface of the stomach wall  46  in close proximity. After coupling, the external bolster  40  is secured to the medical device  10 A in order to prevent future migration of the device and reduce the need for constant reposition or pull on the device. In the preferred embodiments disclosed, the bolster system may be formed separately or as an integral unit, and the segments of the system may be formed of the same, or a similar, composition. One bolster system is described in U.S. Patent Publ. No. 2008/0082081 A1, which is hereby incorporated by reference in its entirety. Other types of bolster systems are described in U.S. Pat. Nos. 5,716,347 and 5,720,734, which are hereby incorporated by reference in their entirety. It is to be understood by one of ordinary skill in the art that, instead of using the described bolster system, the proximal end of the medical device  10 A can reside, and otherwise be fixed, in other locations such as the patient&#39;s nose, and similarly the distal end can reside in other locations such as the jejunum. 
       FIG. 5A  is a close-up view of another embodiment of the bolsters  40 ,  48  and the medical device  10 A partially implanted within the body such that the lumen of the medical device  10 A is in communication with the gastrointestinal system. In particular, at least a portion of the second section  26  of the feeding tube is in direct interface with subcutaneous layers such as at least one of the epidermal surface  42 , the abdominal wall  44  and the stomach wall  46 . A portion  56  of the device  10 A remains external to the body. This external portion  56  provides the desired access to the lumen which is in communication with the gastrointestinal system. Thus, the gastrointestinal system can be accessed without further disruption to the skin. In this example, a portion of the second section  26  includes one or more second therapeutic agents  30  and is preferably positioned across the subcutaneous layers. The second section  26  may even extend below the stomach wall. Because of this position of the second section  26 , the second therapeutic agent  30  can inhibit infection of the contacting portions of the medical device  10 A with the body. A portion of the first section  24  includes the first therapeutic agent  28 , which is positioned within the gastrointestinal system. Because of the position of the first section  24 , the first therapeutic agent  30  can inhibit gastric acid buildup or adverse effects thereof. 
       FIG. 5B  is a close-up view of another embodiment of the bolsters  40 ,  48  and the medical device  10 A partially implanted within the body as described above.  FIG. 5B , however, illustrates a sleeve  60  or barrier coupled to at least one of the bolsters  40 ,  48  such that the sleeve  60  is in direct interface with the subcutaneous layers. The sleeve  60  which has a lumen configured to surround and receive the medical device  10 A can be made of materials similar to the aforementioned materials of the cannula. In this example, a portion of the sleeve  60 , rather than the second section  26 , includes one or more second therapeutic agents  30 , and is preferably positioned across at least one of the epidermal surface  42 , the abdominal wall  44  and the stomach wall  46 . Because of this position of the sleeve  60 , the second therapeutic agent  30  can inhibit infection of the contacting portions of the medical device and/or sleeve with the body. The second section  26  of the medical device preferably does not have any therapeutic agent. A portion of the first section  24  includes the first therapeutic agent  28 , which is positioned within the gastrointestinal system for inhibiting gastric acid buildup or adverse effects thereof. It can be appreciated that the components of the bolster system may also include therapeutic agents for respectively inhibiting infection or gastric acid buildup. 
     For NG tubes, the second section  26  having one or more second therapeutic agents  30  can be associated along various portions of the nasal passage, along various portions of the throat, and/or along various portions of the esophagus. In this instance, the second therapeutic agent is preferably positioned across the respective portions in order for the second therapeutic agent to inhibit infection of the contacting portions of the medical device with the body. For example, the second section can extend from the proximal end of the device for a longitudinal length sufficient to contact portions of the nasal passage and the throat. In another example, the second section may have a first region for contacting a portion of the nasal passage and a second region for contacting a portion the throat, with each of the first and second regions having the same second therapeutic agent or different second therapeutic agents for treating each respective area. 
     The therapeutic agents can be any suitable agents, and need only provide the desired effects. Thus, the therapeutic agents which are associated with the first section  24  can include anti-gastric distress agents that can have a negative effect on the formation or the neutralizing effect on gastric acids. Also, the therapeutic agent which is associated with the second section  26  can have an antimicrobial effect. 
     The therapeutic agents  28 ,  31  associated with the first section  24  can be any suitable anti-gastric distress agent. For example, the therapeutic agents  28 ,  31  can comprise one or more antacids including a variety of alkaline substances. Examples include but not limited to any antacids acceptable to the Food and Drug Administration, such as aluminum carbonate, aluminum hydroxide (or as aluminum hydroxide-hexitol stabilized polymer, aluminum hydroxide-magnesium hydroxide codried gel, aluminum hydroxide-magnesium trisilicate codried gel, aluminum hydroxide-sucrose powder hydrated), aluminum phosphate, aluminum hydroxy carbonate, dihydroxy aluminum sodium carbonate, aluminum magnesium glycinate, dihydroxy aluminum aminoacetate, dihydroxyaluminum aminoacetic acid, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, bismuth subsalicylate, calcium carbonate, calcium phosphate, calcium hydroxide, hydrated magnesium aluminate activated sulfate, magnesium aluminate, magnesium aluminosilicates, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, sodium bicarbonate, potassium bicarbonate, glycine, dried milk solids, sodium carbonate, potassium carbonate, sodium potassium tartrate, and magaldrate with simethicone. A combination of antacids may also be used. Preferably, the antacid is selected from aluminum hydroxide, calcium carbonate, magnesium carbonate, and magnesium hydroxide. Other antacids are known to those skilled in the art and can be found in standard reference literature such as Remington, the Science and Practice of Pharmacy 20th Ed. and the United States Pharmacopeia (USP 26). 
     Antacids can treat an abnormally high acidic gastric acid (pH of about 2) by raising the pH level of the stomach to between 3 and 4. This can neutralize up to 99 percent of the gastric acid, leading to substantial relief from symptoms for most people. Antacids can work within a minute, and can provide relief that ranges from 10 minutes to more than 90 minutes. Generally, antacid compositions containing weaker acid neutralizing agents such as calcium carbonate and aluminum hydroxide are slower acting and consequently do not provide as rapid relief to the discomfort associated with excess or highly acidic gastric acid, but may last longer. More rapid acting antacids may include a stronger acid neutralizing agent, such as, for example, magnesium hydroxide or sodium bicarbonate, but may not last as long. 
     Alternatively, or in combination with the antacids, the therapeutic agent  28 ,  31  can include one or more gastric acid blockers including a variety of H2 blockers. Examples of H2 blockers include cimetidine, famotidine, nizatidine, ranitidine, and ranitidine bismuth citrate. H2 blockers are known to provide longer lasting relief than antacids, up to about 6 to 10 hours or more, depending on the dosage. 
     Alternatively, or in combination with the antacids and/or H2 blockers, the therapeutic agents  28 ,  31  can include one or more proton pump inhibitors. The proton pump inhibitor may be, if desired, in the form of free base, free acid, salt, ester, hydrate, anhydrate, amide, enantiomer, isomer, tautomer, prodrug, polymorph, derivative, or the like, provided that the free base, salt, ester, hydrate, amide, enantiomer, isomer, tautomer, prodrug, or any other pharmacologically suitable derivative is therapeutically active. Examples included omeprazole, dexlansoprazole, esomeprazole, lansoprazole, pantoprazole, pariprazole, leminoprazole, rabeprazole, tenatoprazole, and derivatives thereof. Proton pump inhibitors can provide longer lasting relief than antacids and H2 blockers, for example, up to about 2 to 3 days or more, depending on the dosage. Proton pump inhibitors can be prescribed for treatment of active duodenal ulcers, gastrointestinal ulcers, gastro esophageal reflux disease (GERD), severe erosive esophagitis, poorly responsive symptomatic GERD, and pathological hypersecretory conditions such as Zollinger Ellison syndrome. 
     The therapeutic agent  30  which is associated with the second section  26  can be any suitable antimicrobial agent. Suitable classes of antimicrobial agents include antibiotics, disinfectants, and antiseptics. 
     In a preferred embodiment, the therapeutic agent  30  comprises one or more antibiotics having activity against the common microorganisms associated with colonization and/or infection with indwelling cannula. Examples of suitable classes of antibiotics include tetracyclines, rifamycins, macrolides, penicillins, cephalosporins, other beta-lactam antibiotics, aminoglycosides, chloramphenicol, sulfonamides, glycopeptides, quinolones, fusidic acid, trimethoprim, metronidazole, clindamycin, mupirocin, polyenes, azoles and beta-lactam inhibitors. 
     Examples of specific antibiotics that can be used as the therapeutic agent  30  include minocycline, rifampin, erythromycin, nafcillin, cefazolin, imipenem, aztreonam, gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim, metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin, clarithromycin, ofloxacin, lomefloxacin, norfloxacin, nalidixic acid, sparfloxacin, pefloxacin, amifloxacin, enoxacin, fleroxacin, temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid, amphotericin B, fluconazole, itraconazole, ketoconazole, and nystatin. 
     The therapeutic agent  30  can comprise a combination of two or more antimicrobial agents. In these embodiments, the two or more antimicrobial agents can be located in or on discrete locations within the second section  26 , or the two or more antimicrobial agents can be blended together and uniformly distributed within or on the second section  26 . In a preferred embodiment, rifampin and minocycline are used as the therapeutic agent  30 . The rifampin and minocycline preferably are blended together and evenly distributed either in or on the second section  26 . In a particularly preferred embodiment, discussed below, blended rifampin and minocycline are coated onto the surfaces of second section  26 . With reference to  FIG. 3D , it may be advantageous for one embodiment of the medical device to have a first antimicrobial agent  30 A associated with the interior surface  18  and configured to reduce infection caused by contents entering into, or exiting from, the gastrointestinal system. Further, the embodiment of the medical device includes a second antimicrobial agent  30 B, different than the first, associated with the exterior surface  16  and configured to reduce infection caused by the outside environment or the wall of the gastrostomy. 
       FIG. 6  illustrates one aspect of the medical device  110  that can be included with any of the embodiments described herein, which includes a separator  115  configured to space the first section  124  from the second section  126 . The separator  115 , in addition to physically separating the first and second sections  124 , 126 , provides a visual indicator of the transition between these sections, which can aid fabrication and implantation procedures. The separator  115  can be any suitable separator that provides a separation between the first and second sections  124 , 126 . The separator  115  need only not interfere with implantation in the body. In some embodiments, the separator  115  comprises a portion of the main body  112  that has a reduced diameter as compared to the diameters of the first and second sections  124 , 126 . Examples of other suitable separators include markers, such as bands and dyes disposed within or on the main body and other visual indicators. 
       FIG. 6  also illustrates another aspect of the medical device  110  that can be included with any of the embodiments described herein, which includes a first elongated member  102  and a discrete second elongated member  104  (or a reduced diameter portion of the first tube). The first elongated member is sized to fit within a larger cross-sectional area, while the second elongated member  104  is sized to fit within a smaller cross-sectional area, such as for example the jejunum. 
     Another aspect in  FIG. 6  is the application of therapeutic agents in a side-by-side configuration. For example, the first section  124  of the first elongated member  102  can be configured to interact with the stomach. To this end, the first section  124  can include a therapeutic agent  128  comprising at least one anti-gastric distress agent that is configured to interact more effectively within the stomach. The second elongated member  104  includes another therapeutic agent  131  comprising at least one anti-gastric distress agent that is configured to interact more effectively within the intestines. The second section  126  can also include another therapeutic agent  130  comprising an antimicrobial agent, as described above. Various non-limiting configurations for applications of the therapeutic agents are described above with reference to  FIGS. 2A-2D  and  FIGS. 3A-3D . It is to be understood that the side-by-side configuration can be included in various embodiments of medical devices  10  or  10 A, as well as for the second sections of the various embodiments of the medical devices. 
     The cannula of the medical device, or various sections or elongated members of the cannula, can be made from any suitable material(s) acceptable for use in a medical device and acceptable for the intended use of the medical device. Preferably, the material(s) is able to have one or more therapeutic agents associated with it. Examples of suitable material(s) include polymers, copolymers, plastics, and metals. Typically, the material(s) is a biocompatible polymeric material, including but not limited to silicone, polyurethane, a copolymer of silicone and polyurethane, or a polyamide, such as nylon. The material(s) chosen will depend on several factors, including the intended use of the medical device, the therapeutic agents that will be used in the medical device, the ability of the material to have one or more of the agents associated with it, the permeability of the material to the therapeutic agents, and the ability of the material to be formed into members permeable to the therapeutic agents. The cannula may have portions of different materials, for example the first and second elongated members of  FIG. 6  can be formed of different materials beneficial for their respective implantation. 
     The therapeutic agent(s) can be associated with the respective portions of the medical device in any suitable manner. For example, if a therapeutic agent(s) is bulk distributed in the material of the medical device, a swelling method can be utilized. Alternatively, the therapeutic agent(s) can be added to a melt of bulk material. Once extruded, the medical device will include the therapeutic agent(s) in the material. Further, if different portions of the medical device have therapeutic agents associated in different manners (e.g., bulk distribution versus coating layer), a combination of suitable techniques can be utilized. The separator between the first and second sections of medical devices according to these embodiments, as described above, can advantageously be used to isolate different techniques during fabrication. 
     The therapeutic agent(s) can be releasably associated with the medical device, meaning that the therapeutic agent can be released from the medical device upon implantation in the body of a patient. Preferably, the therapeutic agent(s) is released in a controlled manner. The therapeutic agent(s) can be included in any suitable part or component of the medical device cannula or other components used in association with the medical device. As described in various embodiments, the therapeutic agent(s) can be incorporated within the material of and/or coated onto the surface of one or more of these elements. The therapeutic agent(s) can also be placed in holes, wells or groves formed in the cannula of the medical device. 
     A porous barrier layer can be posited over some, or all, of the therapeutic agent(s) to control the release of the therapeutic agent(s) from the medical device. Multiple porous barrier layers and/or the pore size in the porous barrier layer can be used to control the rate of release of the therapeutic agent(s). One or more therapeutic agents may be impregnated into the material of the medical device or components used therewith. Methods of impregnating therapeutic agents into the structure of non-metallic medical devices are described in U.S. Pat. No. 5,624,704, which is hereby incorporated by reference. One or more therapeutic agents may be impregnated into such medical devices by contacting the medical device with the therapeutic agent in a suitable solvent. In some cases, a penetrating ingredient is also added. 
     In preferred embodiments, one, first anti-gastric distress agent has a faster controlled release rate than another, second anti-gastric distress agent. In other embodiments, one anti-gastric distress agent has a slower treatment rate than another anti-gastric distress agent. Accordingly, the first anti-gastric distress agent is configured to interact with the gastric acid or the gastric acid source to provide quicker relief, while the second anti-gastric distress agent is configured to interact with the gastric acid and/or gastric acid source in order to provide relief over extended periods of time. Examples of combinations may include the first anti-gastric distress agent including a faster acting antacid such as magnesium hydroxide or sodium bicarbonate and the second anti-gastric distress agent including a slower acting antacid such as calcium carbonate or aluminum hydroxide. Alternatively, the first anti-gastric distress agent can include an antacid and the second anti-gastric distress agent can include a H2 blocker and/or a proton pump inhibitor. 
     Selection of the type of anti-gastric distress agent(s), the portions of the medical device containing the anti-gastric distress agent(s) and the manner of attaching the anti-gastric distress agent(s) to the medical device can be chosen to perform a desired therapeutic function upon implantation and, in particular, to achieve the controlled release of the anti-gastric distress agent(s) at a desired rate. 
     Also, if a coating layer is desired, the therapeutic agent(s) can be dip-coated, spray-coated, or coated onto the medical device using any other suitable coating technique. The therapeutic agent(s) can be coated directly on a medical device surface as a separate layer. The therapeutic agent(s) can be bonded to the surface directly via a covalent bond or via a linker molecule which covalently links the therapeutic agent(s) and the surface. The therapeutic agent(s) can also be bound to the surface by ionic, hydrophobic or hydrogen bonding interactions. 
     Alternatively, the therapeutic agent(s) can be attached to a medical device surface within a layer including a carrier material. For example, the therapeutic agent(s) can be mixed with the carrier material, such as a polymer, and applied to a surface of the medical device, for example, by spray or dip coating onto the surface. If the carrier material is biostable, the therapeutic agent(s) can be released by diffusion through the carrier material. If the carrier material is biodegradable, the therapeutic agent(s) can be released upon erosion of the biodegradable carrier material. 
     The carrier material may include a biostable polymer, a biodegradable polymer or any combination thereof. In one embodiment, the therapeutic agent(s) is blended with a biostable polymer to deposit the therapeutic agent(s) within the porous channels within the biostable polymer that permits release of the therapeutic agent(s) from the medical device upon implantation. Alternatively, a blend of the therapeutic agent(s) and a biodegradable polymer can be incorporated within a biostable polymer matrix to permit dissolution of the biodegradable polymer through channels or pores in the biostable polymer matrix upon implantation in the body, accompanied by release of the therapeutic agent(s). In another embodiment, the carrier material includes a biostable polymer, a biodegradable polymer or any combination thereof that is configured to degrade over a certain amount of time such that suitable dosages of therapeutic agent(s) are released periodically to provide relief over a longer implanted time. For example, suitable dosages of therapeutic agent(s) can be released every hour (for example, 0.5%, 1%, 2% or similar increments), every day (5%, 10%, 15% or similar increments) or portions thereof. The percentages may vary due to the type of therapeutic agent, concentration of the therapeutic agent, different expected indwelling times for the medical device, severity of patient&#39;s condition, region of gastrointestinal tract, and size of patient. 
     In another embodiment, for example as illustrated in  FIGS. 2C and 2D , the interior coating  34  of the medical device can be more protected from gastric juices of the gastrointestinal tract than an exterior coating, which may extend the life of the associated therapeutic agent. Further, the interior coating  34  can be configured to interact with the fluid used for flushing the medical device and/or the nutrient fluid used for feeding the patient. The coating may have additional carrier and/or barrier layers that degrade when there is flushing or feeding so that the anti-gastric distress agent is released. The interior coating can include anti-gastric distress agents, and more preferably, an anti-gastric distress agent such as antacid that can be released during flushing or feeding. This is particularly useful since patients may be more apt to require faster acting anti-gastric distress agents during feeding than during other times. In addition, as opposed to interacting with gastric juices of the gastrointestinal tract which may cause faster degradation of the coating, interacting with flushing fluid or feeding fluid may cause a more controlled degradation along the interior coating. In other examples, the exterior of the medical device can allow for a more constant release of an anti-gastric distress agent, while there can be additional intermittent treatment when the medical device is flushed or used for feeding. 
     In accordance with the provisions of the patent statutes, the present invention has been described in what is considered to represent its preferred embodiment. However, it should be noted that the invention can be practiced otherwise than as specifically illustrated and described. Those skilled in the art will recognize that variations and modifications can be made without departing from the true scope and spirit of the preferred embodiments as defined by the claims that follow. It is therefore intended to include within the preferred embodiments all such variations and modifications as fall within the scope of the appended claims and equivalents thereof.