Abstract:
A method and apparatus for delivering a plurality of medicaments in a single delivery vehicle for the management of co-morbid diseases, illnesses and conditions. The present invention provides a novel delivery process for many medicaments. Medicaments may be encapsulated and stored separately within a larger capsule until the time of ingestion, consumption, or the like. Benefits of the present invention include maintaining separation of distinct ingredients within a single capsule and the capability to control the time release of multiple ingredients within the capsule.

Description:
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS 
       [0001]    This is a Continuation-in-part of U.S. patent application Ser. No. 10/804,224, filed Mar. 19, 2004, which is a Continuation-in-part of U.S. patent application Ser. No. 10/786,563, filed on Feb. 26, 2004, which claim priority of U.S. Provisional Patent Application Ser. No. 60/451,150, filed Feb. 27, 2003, entitled, Apparatus and Methods for Delivering a Plurality of Medicaments for Management of a Disease, Illness or Condition Affecting One or More Organ Systems, identifying Frederick H. Miller as the inventor, the contents of which are incorporated by reference herein in their entirety. This application is related to U.S. patent application Ser. No. 10/786,564, filed on Feb. 26, 2004, which claim priority of U.S. Provisional Patent Application Ser. No. 60/450,615, filed on Feb. 27, 2003, entitled, Apparatus and Methods for Delivering a Plurality of Medicaments for Management of Co-Morbid Diseases, Illnesses or Conditions, identifying Frederick H. Miller as the inventor, the contents of which are incorporated by reference herein in their entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to methods for the administration of a plurality of heterogenous chemical and biological compounds to animals and humans using a multi-compartment delivery system for treatment of separate conditions or diseases in one or more organ systems. 
       BACKGROUND OF THE INVENTION 
       [0003]    Administration of chemicals and biomolecules to animals and humans may first appear to be a simple undertaking, however, the contemplation, design, testing, and manufacture of elegant pharmaceutical products requires a thorough integration of medical and pharmacy principles. 
         [0004]    The art and practice of pharmacy can be divided into four distinct divisions. Pharmacology is the study of interactions occurring between the pharmacologic agent, or medicament and specific targeted cells in the body. More specifically, the interaction between an active agent and a cellular receptor along with the resulting change in cell physiology is examined. Medicinal chemistry is largely concerned with the identification of naturally occurring and synthetic compounds which possess medicinal characteristics. Pharmacotherapeutics is the holistic application of pharmacy practice to specific pathologies, illnesses, and other body functions. Finally, Pharmaceutical science ascertains or regulates the composition of medicinal substances, and is largely directed to the development of new mechanisms for delivering chemicals and biomolecules into animals and humans. A sub-category of pharmaceutical science is called pharmacokinetics and sometimes generally referred to as biopharmaceutics. 
         [0005]    A.D.M.E. is an acronym often used to describe the four essential components to pharmaceutical science: absorption, distribution, metabolism, and elimination, respectively. One way to differentiate between pharmacology and pharmaceutical science is that the former is primarily concerned with the effect of the medicament on the body, whereas, the latter is primarily concerned with the delivery and time-course of the medicament on its journey through the body. 
         [0006]    In clinical applications, chemicals and biomolecules are often referred to as active ingredients or medicaments. Medicaments may include “pharmaceuticals, nutraceuticals, biotechnicals, vitamins, minerals and dietary supplements.” Oral administration is the most frequent route for delivery of medicaments. Medicaments may be orally administered in a variety of physical states, including, solid, liquid, dispersion, and gaseous forms. As appreciated, tablets and capsules are the most common vehicle for oral delivery of medicaments. 
         [0007]    Frequently, a medical or surgical patient may receive a plurality of concurrent medicaments. Data has been accumulated to demonstrate that patients undergoing a surgical procedure may receive ten (10) or more medicaments during the surgery and the resulting surgical recovery period. Some patients who have undergone organ transplantation or who have contracted human immunodeficiency virus (HIV) may receive three (3) or more medicaments which require multiple administrations per day. HIV patients often receive many more than three (3) medicaments. These medicaments may be necessary for the treatment of several conditions occurring in a plurality of organ systems or they may be necessary to treat a single condition or some combination thereof. 
         [0008]    In some cases, it may be desirous to combine a plurality of medicaments because of a synergistic interaction between a plurality of medicaments. This synergy may enhance the efficacy of one or more of the medicaments. Medicaments may be combined to increase the intensity of response or efficacy. A plurality of medicaments, in combination, may be homergic (i.e., ellicit the same quality of effect). In many cases, a plurality of homergic medicaments may also be homodynamic (i.e., interact with the same receptor). A plurality of homergic medicaments may be additive, supra-additive and infra-additive. A plurality of combined medicaments which do not produce the same quality of response may be called, heterergic. When heterergy is found to be a positive effect (i.e., at least one medicament enhances the response to another medicament), this may be called synergism and is sometimes called synergy. 
         [0009]    In further cases, it may be desirous to combine a plurality of medicaments to decrease their individual dosages and possibility for toxicity. It may also be desirous to combine a plurality of medicaments to target the treatment of a disease, illness or condition from divergent angles. It may be desirous to combine a plurality of medicaments to minimize the side effects and adverse effects of one or more medicaments. It may be still further desirous to combine a plurality of medicaments to alter the pharmacokinetic characteristics of one or more medicaments. For example, alterations in the absorption, distribution, metabolism or elimination of one or more medicaments. 
         [0010]    Fixed combinations of a plurality of medicaments have been generally disfavored due to any number of perceived disadvantages. These disadvantages may include, for example: (1) complicating the interpretation of safety and efficacy in therapeutic regimens, (2) there may be inter-patient differences to fixed combinations, (3) there may be difficulties in dosage titration, and (4) the delivery platforms for fixed combinations have generally been found to be uneconomical to produce. 
         [0011]    On the other hand, fixed combinations of a plurality of medicaments may lead to several therapeutic advantages, including, for example, but not by way of limitation: (1) increasing patient compliance with therapy, (2) increasing efficacy by optimizing timing of medicaments, (3) minimization of side effects and adverse effects, (4) enhancement of pharmacokinetic characteristics of one or more medicaments in a fixed combination, (5) increased patient quality of life, (6) optimization of institutional resources by minimizing the amount of medicament administrations, and (7) minimizing patient length of stay in institutional facilities by optimizing therapy. 
         [0012]    Prior art therapeutic technologies contain isolated examples of pharmaceutical formulations containing fixed combinations of medicaments. However, therapeutic technologies of the prior art teach a fixed combination, wherein a plurality of medicaments are placed into a single receiving chamber in the delivery formulation (i.e., no separation between the plurality of medicaments). In addition, those skilled in the art developed therapeutic technologies that contemplate the use of a multi-compartment (i.e., multiple-receiving chambered) delivery vehicle for treating  helicobacter pylori -induced peptic ulcer disease. 
         [0013]    In view of the state of the technology as it exists today, generally, therapeutic apparatus and methods are needed to provide a plurality of medicaments for medical and surgical conditions, as well as maintenance of normal health function for delivery to animals and humans using a multi-chambered delivery apparatus. Such apparatus and methods for delivering a plurality of medicaments to animals and humans using a multi-chambered delivery apparatus are contemplated herein. 
       SUMMARY OF THE INVENTION 
       [0014]    A primary object of the present invention is to provide novel delivery apparatus and methods for affecting multiple organ systems in animals or humans using a plurality of medicaments delivered by a pharmaceutical formulation comprising a multi-chambered apparatus. Accordingly, the present invention provides novel delivery apparatus and administration techniques or methods aimed at affecting multiple organ systems in an animal or human using a plurality of medicaments. A delivery apparatus may be in any multi-chambered apparatus, but preferably in a capsular formulation. Thus, a plurality of medicaments may be encapsulated and stored separately within a larger capsule until the time of ingestion, consumption, or the like. Upon consumption, the capsule walls of one or more dividing walls of a capsule may dissolve to release their contents. Different methods of encapsulation may be used to deliver their respective contents, including but not limited to, dissolution, melting, ablation or biodegradation of the encapsulating wall. In certain embodiments and as contemplated herein, the medicaments retained in the multi-compartment capsule may actually diffuse through one or more of the encapsulating walls. 
         [0015]    In accordance with one presently preferred embodiment of the present invention, an encapsulated product may be provided in several parts, including a primary capsule and one or more secondary capsules enclosed therein. In other presently preferred embodiments, a capsule may be provided having separate compartments or sections where ingredients may be stored and released at desired time intervals. More specifically, a process for encapsulating secondary smaller capsules in a larger primary capsule is contemplated hereinbelow. In one presently preferred embodiment, a process in accordance with the present invention may include the steps of
       1. Providing a primary capsule with a receiving chamber, wherein, in certain preferred embodiments, the primary capsule may be provided in two parts, such as a body portion and a cap portion, which may be sealed together to retain ingredients contained therein;   2. Providing one or more secondary capsules having a dimensional size sufficient so that medicaments and the secondary capsule may be introduced within the receiving chamber of the primary capsule, wherein, in selected preferred embodiments, the secondary capsule may also be provided in two parts, such as a body portion and a cap portion, which may be sealed together to retain ingredients contained therein;   3. Filling the receiving chamber of a secondary capsule with one or more medicaments, wherein said medicaments may be the same or different from medicaments in other receiving chambers;   4. Sealing one or more medicaments within the secondary capsule;   5. Inserting the secondary capsule into at least a portion of the receiving chamber of the primary capsule;   6. Filling the body portion of the primary capsule, housing one or more secondary filled capsules, with one or more medicaments; and   7. Sealing one or more medicaments and one or more secondary capsules within a receiving chamber of the primary capsule.       
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0023]    The objects and features of the present invention will become more fully apparent from the following description, taken in conjunction with the accompanying drawings and appendicies. Understanding that the Figures depict presently preferred embodiments of the present invention and are, therefore, not to be considered limiting of its scope, the invention will be described with additional specificity and detail through use of the accompanying drawings and appendicies in which: 
           [0024]      FIG. 1  is flow chart illustrating several preferred embodiments of the present invention, wherein said embodiments originating from five (5) proprietary products belonging to Pfizer, Incorporated; 
           [0025]      FIG. 2  is flow chart illustrating several preferred embodiments of the present invention, wherein said embodiments originating from five (5) proprietary products belonging to Glaxo SmithKline, P.L.C; 
           [0026]      FIG. 3  is flow chart illustrating several preferred embodiments of the present invention, wherein said embodiments originating from five (5) proprietary products belonging to Merck &amp; Co; 
           [0027]      FIG. 4  is flow chart illustrating several preferred embodiments of the present invention, wherein said embodiments originating from five (5) proprietary products belonging to AstraZeneca, P.L.C; and 
           [0028]      FIG. 5  is flow chart illustrating several preferred embodiments of the present invention, wherein said embodiments originating from five (5) proprietary products belonging to Novartis, Incorporated. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0029]    It will be readily understood that the components of the present invention as detailed below, may be arranged and designed in a wide variety of different configurations and steps. Thus, the description herein is not intended to limit the scope of the invention, but is merely representative of certain presently preferred embodiments in accordance with the invention and its inherent inventive concepts. Those of ordinary skill in the art will, of course, appreciate that various modifications to the details herein may easily be made without departing from the essential characteristics of the invention, as described. Thus, the following information is intended only by way of example, and simply illustrates certain presently preferred embodiments consistent with the invention. 
         [0030]    Appendix I contains a list of diseases, illnesses and conditions which are known to affect several organ systems and a list of medicaments which may be helpful in managing said diseases, illnesses and conditions, the contents of Appendix I being incorporated herein by reference in their entirety. 
         [0031]    Referring to generally to Appendix I, it may be demonstrated that as medical and pharmacy knowledge has continued to expand exponentially, new medicaments, new classes of medicaments and new delivery technologies are becoming available for use in animals and humans who experience particular medical diseases, illnesses or conditions. A disease, illness, or condition may affect one or more organ systems in an animal or human. Organ systems may include, for example: (1) autonomic, (2) cardiovascular, (3) neurological, (4) gastro-intestinal, (5) respiratory, (6) renal system, (7) psychiatric, (8) endocrine, (9) gynecologic, (10) urologic, (11) immunologic, (12) bone and joint systems, (13) ear, nose, and throat, (14) dermatologic, (15) hematologic, (16) infectious defense and (17) nutrition and metabolism. In an animal or human who may be suffering from one disease, illness or condition, it is common to also be suffering from a disease, illness or condition affecting one or more of the other organ system(s). These concomitant diseases, illnesses or conditions occurring within a single animal or human are often labeled as “co-morbidities”, a term often shortened and referred to as “co-morbid.” 
         [0032]    New medicaments and delivery technologies are providing patients and their health care practitioners with unprecedented therapeutic options in managing diseases, illnesses and conditions. In spite of this sophistication, there has been no effort to develop new methods of using fixed combinations of medicaments for therapy of co-morbid diseases, illnesses or conditions. Moreover, there has been no effort to develop new methods of using fixed combinations of medicaments for management of a single disease, illness or condition affecting one or more organ system(s). The aforementioned fixed combinations may include a plurality of medicaments, which may be newly discovered and developed, or have been known for sometime or some combination of medicaments thereof. In any regard, said fixed combinations have not previously been contemplated in the art. 
         [0033]    The following examples will illustrate the invention in further detail. It will be readily understood that the various plurality of medicaments that may be introduced into the receiving chambers of the multi-compartment vehicles of the present invention, as generally described and illustrated in the Examples herein, are to be viewed as exemplary of the principles of the present invention, and not as restrictive to a particular structure or process for implementing those principles. Thus, the following more detailed description of the presently preferred embodiments of the methods, formulations, and compositions of the present invention, as represented in Examples I-V, is not intended to limit the scope of the invention, as claimed, but is merely representative of presently preferred embodiments of the invention. 
       Example I 
       [0034]    Referring to  FIG. 1 , in one presently preferred embodiment of the present invention, a plurality of medicaments are delivered in a single vehicle for management of co-morbid diseases, illnesses or conditions. More particularly, a plurality of medicaments comprising an HMG CoA Reductase inhibitor, for example, atorvastatin (LIPITOR® manufactured by Pfizer, Inc.), and a serotonin reuptake inhibitor, for example, sertraline (ZOLOFT® manufactured by Pfizer, Inc.), may be combined into a single delivery apparatus, for example, a multi-compartment capsule. 
         [0035]    In the presently preferred embodiment, a therapeutically effective amount of atorvastatin (LIPITOR® manufactured by Pfizer, Inc.), may be introduced into a receiving chamber of a secondary capsule. The base and cap of the secondary capsule may then be sealed using any available conventional means readily known to those skilled in the art. The secondary capsule may then be introduced into a receiving chamber in a primary capsule. A therapeutically effective amount of sertraline (ZOLOFT® manufactured by Pfizer, Inc.) may be introduced into the receiving chamber of the primary capsule. The base and cap of the primary capsule may then be sealed using any available conventional means readily known to those skilled in the art. 
         [0036]    A capsular format of the present invention may include the following composition: 
         [0000]    
       
         
               
               
             
           
               
                   
               
             
             
               
                 Primary Capsule: 
                   
               
               
                 sertraline (ZOLOFT ® manufactured by Pfizer, Inc.) 
                 100 mg 
               
               
                 [dosage range 50-200 mg/day] 
               
               
                 Secondary Capsule: 
               
               
                 atorvastatin (LIPITOR ® manufactured by Pfizer, Inc.) 
                  20 mg 
               
               
                 [dosage range 10-80 mg/day] 
               
               
                   
               
             
          
         
       
     
         [0037]    The incorporation of time-release coatings to vary the release rates of the medicaments (e.g., sertraline (ZOLOFT® manufactured by Pfizer, Inc.) and atorvastatin (LIPITOR® manufactured by Pfizer, Inc.)) in the primary and secondary capsules, respectively, of the multi-compartment capsule may be used to target key time intervals or events when the body may be most able to utilize the named active ingredients. For example, HMG CoA Reductase Inhibitors are known to as much as a 70% increase in efficacy when administered in the evening hours. Thus, by varying the composition of the secondary capsular wall, release of the contents of the secondary capsule may be targeted to an optimal delivery time. A differential release between the primary capsule and secondary capsule may therefore optimize management of co-morbid conditions in a patient. The patient is able to take a single daily administration vehicle, which provides a plurality of medicaments for managing co-morbid conditions. Thus, the incorporation of time-release coatings in the encapsulation process when forming a multi-compartment capsule may be specifically designed to fit the needs and desires of numerous different users having similar conditions that are being targeted for treatment. It is intended, therefore, that the examples provided herein be viewed as exemplary of the principles of the present invention, and not as restrictive to a particular structure or method for implementing those principles. 
       Example II 
       [0038]    Referring to  FIG. 2 , in one presently preferred embodiment of the present invention, a plurality of medicaments are delivered in a single vehicle for management of co-morbid diseases, illnesses or conditions. More particularly, a plurality of medicaments comprising a thiazolidinedione derivative, for example, rosiglitazone (AVANDIA® manufactured by Glaxo SmithKline), and a serotonin reuptake inhibitor, for example, paroxetine (PAXIL® manufactured by Glaxo SmithKline) may be combined into a single delivery apparatus, for example, a multi-compartment capsule. 
         [0039]    In the presently preferred embodiment, a therapeutically effective amount of paroxetine (PAXIL® manufactured by Glaxo SmithKline) may be introduced into a receiving chamber in a secondary capsule. The base and cap of the secondary capsule may then be sealed using any available means readily known to those skilled in the art. A therapeutically effective amount of rosiglitazone (AVANDIA® manufactured by Glaxo SmithKline) may be introduced into a receiving chamber in a primary capsule. The secondary capsule may then be introduced into a receiving chamber in a primary capsule. The primary capsule may then be sealed using any available means readily known to those skilled in the art. 
         [0040]    A capsular format of the present invention may include the following composition: 
         [0000]    
       
         
               
               
             
           
               
                   
               
             
             
               
                 Primary Capsule: 
                   
               
               
                 rosiglitazone (AVANDIA ® manufactured by Glaxo 
                  4 mg 
               
               
                 SmithKline) [dosage range 4-8 mg/day] 
               
               
                 Secondary Capsule: 
               
               
                 paroxetine (PAXIL ® manufactured by Glaxo SmithKline) 
                 20 mg 
               
               
                 [dosage range 20-60 mg/day] 
               
               
                   
               
             
          
         
       
     
         [0041]    The incorporation of time-release coatings to varying the release rates of the medicaments (e.g., rosiglitazone (AVANDIA® manufactured by Glaxo SmithKline) and paroxetine (PAXIL® manufactured by Glaxo SmithKline)) in the primary and secondary capsules, respectively, of the multi-compartment capsule may be used to target key time intervals or events when the body may be most able to utilize the named active ingredients. For example, paroxetine (PAXIL® manufactured by Glaxo SmithKline) is known to have sedating effects similar to antihistamines. Therefore, to minimize these effects on activities of daily living, paroxetine (PAXIL® manufactured by Glaxo SmithKline) is recommended for administration in the evening hours. Thus, by varying the composition of the secondary capsule wall, release of the contents of the secondary capsule may be targeted to an optimal time. A differential release between the primary capsule and secondary capsule may therefore optimize management of co-morbid conditions in a patient. The patient is able to take a single daily administration vehicle, which provides a plurality of medicaments for managing co-morbid conditions. Thus, the incorporation of time-release coatings in the encapsulation process when forming a multi-compartment capsule may be specifically designed to fit the needs and desires of numerous different users having similar conditions that are being targeted for treatment. It is intended, therefore, that the examples provided herein be viewed as exemplary of the principles of the present invention, and not as restrictive to a particular structure or method for implementing those principles. 
       Example III 
       [0042]    Referring to  FIG. 3 , in one presently preferred embodiment of the present invention, a plurality of medicaments are delivered in a single vehicle for management of co-morbid diseases, illnesses or conditions. More particularly, a plurality of medicaments comprising a bisphosphonate, for example, alendronate (FOSAMAX® manufactured by Merck &amp; Co.) and an HMG CoA Reductase Inhibitor, for example, simvastatin (ZOCOR® manufactured by Merck &amp; Co.) may be combined into a single delivery apparatus, for example, a multi-compartment capsule. 
         [0043]    In the presently preferred embodiment, a therapeutically effective amount of simvastatin (ZOCOR® manufactured by Merck &amp; Co.) may be introduced into a receiving chamber in a secondary capsule. The base and cap of the secondary capsule may then be sealed using any available conventional means readily known to those skilled in the art. The secondary capsule may then be introduced into a receiving chamber in a primary capsule. A therapeutically effective amount of alendronate (FOSAMAX® manufactured by Merck &amp; Co.) may be introduced into a receiving chamber in a primary capsule. The base and cap of the primary capsule may then be sealed using any available conventional means readily known to those skilled in the art. 
         [0044]    A capsular format of the present invention may include the following composition: 
         [0000]    
       
         
               
               
             
           
               
                   
               
             
             
               
                 Primary Capsule: 
                   
               
               
                 alendronate (FOSAMAX ® manufactured by Merck &amp; Co.) 
                  5 mg 
               
               
                 [dosage range 5-10 mg/day] 
               
               
                 Secondary Capsule: 
               
               
                 simvastatin (ZOCOR ® manufactured by Merck &amp; Co.) 
                 40 mg 
               
               
                 [dosage range 5-80 mg/day] 
               
               
                   
               
             
          
         
       
     
         [0045]    The incorporation of time-release coatings to varying the release rates of the medicaments (e.g., alendronate (FOSAMAX® manufactured by Merck &amp; Co.) and simvastatin (ZOCOR® manufactured by Merck &amp; Co.)) in the primary and secondary capsules, respectively, of the multi-compartment capsule may be used to target key time intervals or events when the body may be most able to utilize the named active ingredients. For example, HMG CoA Reductase Inhibitors are known to as much as a 70% increase in efficacy when administered in the evening hours. Therefore, to maximize its effects, simvastatin (ZOCOR® manufactured by Merck &amp; Co.) is recommended for administration in the evening hours. Moreover, alendronate (FOSAMAX® manufactured by Merck &amp; Co.) is known to have an extremely low bioavailability following oral administration. Alendronate (FOSAMAX® manufactured by Merck &amp; Co.) is recommended to be taken on an empty stomach upon waking in the morning. It is also recommended that the patient stay in an upright position for at least 30 minutes following administration. Therefore the presently preferred embodiment of the present invention is ideally suited for increasing patient compliance. 
         [0046]    Thus, by varying the composition of the secondary capsule wall, release of the contents of the secondary capsule may be targeted to an optimal delivery time. A differential release between the primary capsule and secondary capsule may therefore optimize management of co-morbid conditions in a patient. The patient is able to take a single daily administration vehicle, which provides a plurality of medicaments for managing co-morbid conditions. Thus, the incorporation of time-release coatings in the encapsulation process when forming a multi-compartment capsule may be specifically designed to fit the needs and desires of numerous different users having similar conditions that are being targeted for treatment. It is intended, therefore, that the examples provided herein be viewed as exemplary of the principles of the present invention, and not as restrictive to a particular structure or method for implementing those principles. 
       Example IV 
       [0047]    Referring to  FIG. 4 , in one presently preferred embodiment of the present invention, a plurality of medicaments are delivered in a single vehicle for management of co-morbid diseases, illnesses or conditions. More particularly, a plurality of medicaments comprising a beta-adrenergic receptor antagonist, for example, metoprolol (TOPROL XL® manufactured by AstraZeneca) and a proton pump inhibitor, for example, omeprazole (PRILOSEC® manufactured by AstraZeneca) may be combined into a single delivery apparatus, for example, a multi-compartment capsule. 
         [0048]    In the presently preferred embodiment, a therapeutically effective amount of omeprazole (PRILOSEC® manufactured by AstraZeneca) may be introduced into a receiving chamber in a secondary capsule. The base and cap of the secondary capsule may then be sealed using any available conventional means readily known to those skilled in the art. The secondary capsule may then be introduced into a receiving chamber in a primary capsule. A therapeutically effective amount of metoprolol (TOPROL XL® manufactured by AstraZeneca) may be introduced into a receiving chamber in a primary capsule. The base and cap of the primary capsule may then be sealed using any available conventional means readily known to those skilled in the art. 
         [0049]    A capsular format of the present invention may include the following composition: 
         [0000]    
       
         
               
               
             
           
               
                   
               
             
             
               
                 Primary Capsule: 
                   
               
               
                 metoprolol (TOPROL XL ®manufactured by AstraZeneca) 
                 100 mg 
               
               
                 [dosage range 25-200 mg/day] 
               
               
                 Secondary Capsule: 
               
               
                 omeprazole (PRILOSEC ® manufactured by AstraZeneca) 
                  20 mg 
               
               
                 [dosage range 20-80 mg/day] 
               
               
                   
               
             
          
         
       
     
         [0050]    The incorporation of time-release coatings to varying the release rates of the medicaments (e.g., metoprolol (TOPROL XL® manufactured by AstraZeneca) and omeprazole (PRILOSEC® manufactured by AstraZeneca)) in the primary and secondary capsules, respectively, of the multi-compartment capsule may be used to target key time intervals or events when the body may be most able to utilize the named active ingredients. For example, the peak acid secretion in the gastrointestinal system is believed to occur during sleep. Proton pump inhibitors may therefore be more efficacious when administered in the evening hours and thus allowing a peak systemic concentration to coincide with higher levels of acid production. Therefore, to maximize its effects, omeprazole (PRILOSEC® manufactured by AstraZeneca) is recommended for administration in the evening hours. Therefore the presently preferred embodiment of the present invention is ideally suited for increasing patient compliance. 
         [0051]    Thus, by varying the composition of the secondary capsule wall, release of the contents of the secondary capsule may be targeted to an optimal delivery time. A differential release between the primary capsule and secondary capsule may therefore optimize management of co-morbid conditions in a patient. The patient is able to take a single daily administration vehicle, which provides a plurality of medicaments for managing co-morbid conditions. Thus, the incorporation of time-release coatings in the encapsulation process when forming a multi-compartment capsule may be specifically designed to fit the needs and desires of numerous different users having similar conditions that are being targeted for treatment. It is intended, therefore, that the examples provided herein be viewed as exemplary of the principles of the present invention, and not as restrictive to a particular structure or method for implementing those principles. 
       Example V 
       [0052]    Referring to  FIG. 5 , in one presently preferred embodiment of the present invention, a plurality of medicaments are delivered in a single vehicle for management of co-morbid diseases, illnesses or conditions. More particularly, a plurality of medicaments comprising an acetylcholinesterase inhibitor, for example, rivastigmine (EXELON® manufactured by Novartis, A.G) and an angiotensin II receptor antagonist, for example, valasartan (DIOVAN®manufactured by Novartis, A.G) may be combined into a single delivery apparatus, for example, a multi-compartment capsule. 
         [0053]    In the presently preferred embodiment, a therapeutically effective amount of valasartan (DIOVAN® manufactured by Novartis, A.G) may be introduced into a receiving chamber in a secondary capsule. The base and cap of the secondary capsule may then be sealed using any available conventional means readily known to those skilled in the art. The secondary capsule may then be introduced into a receiving chamber in a primary capsule. A therapeutically effective amount of rivastigmine (EXELON® manufactured by Novartis, A.G) may be introduced into a receiving chamber in a primary capsule. The base and cap primary capsule may then be sealed using any available conventional means readily known to those skilled in the art. 
         [0054]    A capsular format of the present invention may include the following composition: 
         [0000]    
       
         
               
               
             
           
               
                   
               
             
             
               
                 Primary Capsule: 
                   
               
               
                 rivastigmine (EXELON ® manufactured by Novartis, A.G) 
                  9 mg 
               
               
                 [dosage range 6-12 mg/day] 
               
               
                 Secondary Capsule: 
               
               
                 valasartan (DIOVAN ®manufactured by Novartis, A.G) 
                 120 mg 
               
               
                 [dosage range 80-320 mg/day] 
               
               
                   
               
             
          
         
       
     
         [0055]    The incorporation of time-release coatings to varying the release rates of the medicaments (e.g., rivastigmine (EXELON® manufactured by Novartis, A.G) and valasartan (DIOVAN® manufactured by Novartis, A.G)) in the primary and secondary capsules, respectively, of the multi-compartment capsule may be used to target key time intervals and optimize patient compliance. For example, rivastigmine (EXELON® manufactured by Novartis, A.G) is labeled for use in patients suffering from Alzheimer&#39;s disease, a type of dementia. These patients often have difficulty remembering tasks associated with activities of daily living. It is known that these patients may forget to take their medicines. By reducing the daily administration of medicine in this patient, there may be improved patient compliance. Therefore the presently preferred embodiment of the present invention is ideally suited for increasing patient compliance. 
         [0056]    Thus, by varying the composition of the secondary capsule wall, release of the contents of the secondary capsule may be targeted to an optimal time. A differential release between the primary capsule and secondary capsule may therefore optimize management of co-morbid conditions in a patient. The patient is able to take a single daily administration vehicle, which provides a plurality of medicaments for managing co-morbid conditions. Thus, the incorporation of time-release coatings in the encapsulation process when forming a multi-compartment capsule may be specifically designed to fit the needs and desires of numerous different users having similar conditions that are being targeted for treatment. It is intended, therefore, that the examples provided herein be viewed as exemplary of the principles of the present invention, and not as restrictive to a particular structure or method for implementing those principles. 
         [0057]    As can be seen above, various embodiments of the present invention can be utilized in specific medical applications. By way of example only and not by way of limitation, the present invention can be practiced to prepare delivery devices for use in chemotherapy to address/treat, by way of example and not by limitation, the following aspects of chemotherapy: psychological, timing (to coincide with tumor growth for example) route of administration, nausea, vomiting (CINV), compliance, and cost (e.g. reduce hospital management of patients, reduce the number of “repeat” drug doses due to patient vomiting, etc.). Still further, the just mentioned aspects are not limited to chemotherapy, as the present invention can be practiced to address common aspects between chemotherapy and other treatments. 
         [0058]    Further by way of examples, capsules containing Zofran (ondansertron), Temodar (temozolomide) can be made. 
         [0059]    Still further, the present invention can be used in cardiovascular treatments, for example hypertension, heart failure, and heart rhythm disorders. Also, the present invention can be used in immunology (e.g. transplant rejections, auto-immune disorders, etc.). The present invention can be used to treat neurological disorders (such as Parkinson&#39;s disease, dementia, stroke, epilepsy, and migraine headache, etc.), psychiatric disorders (schizophrenia, bipolar disease, depression, anxiety, ADHD/ADD, Addictions, etc.), infectious diseases (fungal, bacterial, viral (HIV), etc.), and in anesthesiology (induction anesthesia, local anesthesia). Furthermore, the present invention has application in endocrinology (cholesterol, diabetes, hormone replacement therapy, thyroid dysfunction, oral contraception, obesity, etc.), dermatology (onychomycosis, acne, rosaceae, psoriasis, etc.), rheumatology (arthritis, gout, osteoporosis/Osteomalacia), respiratory fields (asthma, emphysema, cystic fibrosis, etc.), gastro-intestinal fields (gastro-esophageal reflux disease, ulcer prophylaxis, crohn&#39;s disease, inflammatory bowel disease, etc.), chronic renal failure (vitamin and mineral replacement, blood pressure regulation, diabetes, depression, etc.), genito-urinary (enlarged prostate/BPH, overactive bladder, erectile dysfunction, feminine yeast infections, etc.) and hematology-oncology (thromboembolous, hermatopoeisis, neoplastic disease, nausea/vomiting). 
         [0060]    The present invention may be utilized for dual/multiple disease state therapy with one capsule, dual/multiple organ system therapy with one capsule, enhanced pharmacoeconomic delivery, temporal/circadian optimized delivery, sports nutrition, sports therapy, athletic performance enhancement and law enforcement and military applications. 
         [0061]    The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative, and not restrictive. One skilled in the art will recognize that this technology may be applicable for providing a wide variety a plurality of medicaments in a single delivery vehicle for management of co-morbid diseases, illnesses or conditions. 
         [0062]    Other drugs that may be combined, into a single delivery apparatus, for example, a multi-compartment capsule, according to the present invention include, by way of example, Lipitor (by Pfizer), Prilosec (by Astra Zenica), Prevacid (by Tap), Zocor (by Merck), Celebrex (by Searle), Zoloft (by Pfizer), Paxil (by GSK,) Vioxx (by Merck), Prozac (by Lilly), Augmentin (by GSK), Norvasc (by Pfizer), Zyprexa (by Lilly) EPO (by Amgen), Cipro (by Bayer), Lotrel (by Novartis), Topamx (by Johnson and Johnson), Glucotrol XL (by Pfizer), Claritin (by Schwiring), Wellbutrin SR (by GSK), Difucan (by Pfizer), Prilosec/Nexium (by Astra Zenica), Accupril (by Pfizer), Zofran (by GSK), Zithromax (by Pfizer), Imitrex (by GSK), Fosamax (by Merck) Zytrec (by Pfizer), Neurontin (by Pfizer), Pravachol (by BMS), Depakote (by Abbott). Some embodiments of the invention include two or more of the just mentioned drugs combined in a single delivery apparatus, while other embodiments of the invention include only one of the just mentioned drugs combined with another pharmaceutical and/or nutricutical and/or other substances, such as, by way of example and not by way of limitation, one or more of the pharmaceuticals and/or nutraceuticals and/or other substances listed in Appendix I. Still further, some embodiments of the invention include two or more of the pharmaceuticals and/or nutraceuticals and/or other substances listed in Appendix I in a single delivery apparatus. In this regard, the present invention includes an apparatus and a method for delivering a plurality of the medicaments listed in Appendix I for management of co-morbid diseases, illnesses, and/or conditions, as would be understood by one of ordinary skill in the art furnished with the teachings of the present invention. 
         [0063]    It is further noted that a singe delivery apparatus, to deliver a plurality of medicaments for management of co-morbid diseases, illnesses or conditions according to the present invention may include a deliver apparatus as is disclosed in U.S. application Ser. No. 10/369,427, filed Feb. 18, 2003, entitled “MULTI-PHASE, MULTI-COMPARTMENT CAPSULAR DELIVERY APPARATUS AND METHODS FOR USING SAME,” the contents of which are hereby incorporated by reference in their entirety; U.S. application Ser. No. 10/368,951, filed Feb. 18, 2003, entitled “PROCESS FOR ENCAPSULATING MULTI-PHASE, MULTI-COMPARTMENT CAPSULES,” the contents of which are hereby incorporated by reference in their entirety; U.S. application Ser. No. 10/369,244, filed on Feb. 18, 2003, and entitled “MULTI-PHASE, MULTI-COMPARTMENT CAPSULAR DELIVERY APPARATUS FOR THERAPEUTIC COMPOSITIONS AND METHODS FOR USING SAME” the contents of which are hereby incorporated by reference in their entirety; U.S. application Ser. No. 10/369,247, filed Feb. 18, 2003, and entitled “PROCESS FOR ENCAPSULATING MULTI-PHASE, MULTI-COMPARTMENT CAPSULES FOR THERAPEUTIC COMPOSITIONS,” the contents of which are hereby incorporated by reference in their entirety; and PCT/US/03/10816 filed Apr. 9, 2003, and entitled “MULTI-PHASE, MULTI-COMPARTMENT CAPSULAR SYSTEM”, the contents of which are hereby incorporated by reference in their entirety, the apparatus delivering these pharmaceuticals and/or nutraceuticals and/or other substances containing them in a common phase (e.g., all solid, all liquid, etc.), or in a multi-phase (e.g., one substance solid and one substance liquid; two substances solid and one substance liquid, etc.) state as disclosed in the just mentioned references. 
       APPENDIX I 
     Medicaments Acting on the Autonomic Nervous System 
       [0064]    Adrenergic Medicaments 
         [0065]    Cholinergic Medicaments 
         [0066]    Direct Muscarinic Agonists Choline Esters
       acetylcholine   bethanechol (Urecholine)   carbachol   methacholine (Provocholine)       
 
         [0071]    Alkaloids
       muscarine   pilocarpine (Pilocar)       
 
         [0074]    Direct Nicotinic Agonist
       nicotine       
 
         [0076]    Acetylcholinesterase Inhibitors Acetylcholinesterase Inhibitors (“Reversible”)
       edrophonium (Tensilon)   neostigmine (Prostigmin)   physostigmine (Antilirium)       
 
         [0080]    Acetylcholinesterase Inhibitors (“Irreversible”)
       (diisopropylflurorphosphate DFP)   echothiophate (Phospholine)   isoflurophate (Floropryl)       
 
         [0084]    Muscarinic Antagonists Atropine
       ipratropium (Atrovent)   pirenzepine   scopolamine       
 
         [0088]    2-PAM: Acetylcholinesterase React ivator Pralidoxime (Protopam) {2-PAM}:peripheral acetylcholinesterase reactivator for certain phosphoryl-enzyme complexes 
         [0089]    Ganglionic Blockers
       hexamethonium   mecamylamine (Inversine)   trimethaphan       
 
         [0093]    Catecholamines
       dobutamine (Dobutrex)   dopamine (Intropin)   epinephrine   isoproterenol (Isuprel)   norepinephrine (Levophed)       
 
         [0099]    Direct Adrenoceptor Agonist Medicaments
       albuterol (Ventolin, Proventil)   clonidine (Catapres)   methoxamine (Vasoxyl)   oxymetazoline (Afrin)   phenylephrine (Neo-Synephrine)   ritodrine (Yutopar)   salmeterol (Serevent)   terbutaline (Brethine)       
 
         [0108]    Indirect-Acting Sympathomimetic Medicaments
       amphetamine   cocaine   ephedrine, Pseudoephedrine   tyramine       
 
         [0113]    Alpha-Adrenoceptor Antagonists Medicaments
       doxazosin (Cardura)   labetalol (Trandate, Normodyne)   phenoxybenzamine (Dibenzyline)   phentolamine (Regitine)   prazosin (Minipress)   terazosin (Hytrin)   tolazoline (Priscoline)   trimazosin   yohimbine (Yocon)       
 
         [0123]    β-Adrenoceptor antagonist Medicaments
       atenolol (Tenormin)   butoxamine   esmolol (Brevibloc)   labetalol (Trandate, Normodyne)   metoprolol (Lopressor)   nadolol (Corgard)   pindolol (Visken)   propranolol (Inderal)   timolol (Blocadren)       
 
         [0133]    Adrenergic Neuron Blocking Medicaments
       guanethidine (Ismelin)   reserpine       
 
       Cardiovascular System Disorders Cardiovascular Testing and Diagnosis 
       [0136]    Hypertension (HTN) 
         [0137]    Heart Failure 
         [0138]    Ischemic Heart Disease 
         [0139]    Myocardial Infarction 
         [0140]    Arrhythmias 
         [0141]    Isolated Diastolic Heart Failure and Cardiomyopathies 
         [0142]    Cardiac Transplantation 
         [0143]    Venous Thromboembolism 
         [0144]    Stroke 
         [0145]    Hyperlipidemia 
         [0146]    Peripheral vascular disease 
         [0147]    Diuretics
       carbonic-anhydrase inhibitors   loop diuretics   osmotic diuretics   potassium sparing diuretics   thiazide diuretics       
 
       Anitiarrhythmic Medicaments 
       [0153]    Sodium Channel blocking agents
       disopyramide (Norpace)   flecainide (Tambocor)   ibutilide   lidocaine (Xylocaine)   mexiletine (Mexitil)   moricizine (Ethmozine)   procainamide (Pronestyl, Procan)   propafenone (Rythmol)   quinidine   tocainide (Tonocard)       
 
         [0164]    Calcium Channel blocking agents
       bepridil (Vasocor)   diltiazem (Cardizem)   verapamil (Isoptin, Calan)       
 
         [0168]    Adrenergic receptor antagonists
       propranolol (Inderal)       
 
         [0170]    Other medicaments
       adenosine (Adenocard)   amiodarone (Cordarone)   bretylium (Bretylol)   disopyramide (Norpace)   esmolol (Brevibloc)   sotalol (Betapace)       
 
       Hypolipidemic Medicaments 
       [0177]    HMG CoA Reductase Inhibitors
       atorvastatin (Lipitor)   cerivistatin (Baycol)   lovastatin (Mevacor)   pravastatin (Pravochol)   simvastatin (Zocor)       
 
         [0183]    Bile-acid sequestrants
       cholestyramine (Questran)   colestipol (Colestid)       
 
         [0186]    Fibric acids
       clofibrate   fenofibrate (Tricor)   gemfibrozil (Lopid)       
 
         [0190]    niacin, nicotinic acid 
         [0191]    probucol (Lorelco) 
       Antihypertensive Medicaments 
       [0192]    Adrenergic receptor antagonists
       acebutalol (Sectral)   atenolol (Tenormin)   betaxolol (Betoptic)   bisoprolol (Zebeta)   carteolol (Cartrol)   clonidine (Catapres)   labetalol (Normodyne)   metoprolol (Toprol)   penbutalol (Levatol)   pindolol (Visken)   prazosin (Minipres)   propranolol (Inderal)   terazosin (Hytrin)   timolol (Timoptic)       
 
         [0207]    Calcium Channel Antagonists
       amlodipine (Norvasc)   diltiazem (Cardizem)   felodipine (Plendil)   isradipine (Dynacirc)   nicardipine (Cardene)   nifedipine (Procardia)   nimodipine (Nimotop)   nisoldipine (Sular)   verapamil (Isoptin, Calan)       
 
         [0217]    Angiotensin Converting Enzyme (ACE) Inhibitor
       benazepril (Lotensin)   bepridil (Vascor)   captopril (Capoten)   enalapril (Vasotec)   fosinopril (Monopril)   lisinopril (Prinivil, Zestril)   moexipril (Univase)   quinapril (Accupril)   ramipril (Altace)       
 
         [0227]    Angiotensin II Receptor Antagonists
       losartan (Cozaar)   valasartan (Diovan)       
 
         [0230]    Diuretics
       amiloride (Midamor)   bumetanide (Bumex)   chlorothalidone (Hygroton)   ethacrynic acid (Edecrin)   furosemide (Lasix)   hydrochlorothiazide (Diuril)   indapamide (Lozol)   metolazone (Zaroxolyn)   torsemide (Demadex)   triamterene       
 
         [0241]    Other Agents
       hydralazine (Apresoline)   minoxidil (Rogaine)   nitroprusside (Nipride)   prazosin (Minipres)   reserpine   sotalol (Brevibloc)   spironolactone (Aldactone)   terazosin (Hytrin)       
 
       Antianginal Medicaments 
       [0250]    Organic nitrates 
         [0251]    Calcium Channel Antagonists 
         [0252]    Adrenergic Receptor Antagonists 
         [0253]    amyl nitrite 
         [0254]    erythrityl tetranitrate 
         [0255]    isosorbide dinitrate (Isordil) 
         [0256]    nitroglycerin 
         [0257]    pentaerythritol tetranitrate 
       Congestive Heart Failure Medicaments 
       [0258]    phosphodiesterase (PDE) inhibitors
       amrinone (Inocor)   milrinone (Primacor)       
 
         [0261]    carvedilol (Coreg) 
         [0262]    cardiac glycosides
       digitoxin   digoxin       
 
         [0265]    diuretics 
         [0266]    ACE Inhibitors 
         [0267]    dobutamine 
         [0268]    dopamine 
       Respiratory System Disorders Asthma 
       [0269]    Chronic Obstructive Lung Disease (COLD)/Chronic Obstructive Pulmonary Disease (COPD) 
         [0270]    Acute Respiratory Distress Syndrome (ARDS) 
         [0271]    Drug-Induced Pulmonary Disease 
         [0272]    Cystic Fibrosis 
         [0273]    corticosteroids
       beclomethasone   betamethasone   cortisone   dexamethasone   fluticasone (Flovent/Flonase)   hydrocortisone   methylprednisolone   prednisolone   prednisone   triamcinolone       
 
         [0284]    sympathomimetics
       albuterol (Proventil/Ventolin)   salmeterol (Serevent)       
 
         [0287]    muscarinic antagonists
       ipratropium (Combivent)       
 
         [0289]    leukotriene pathway inhibitors
       montelukast (Singulair)   zafirlukast (Accolate)       
 
         [0292]    mast cell stabilizers
       cromolyn (Intal)       
 
         [0294]    methylxanthines
       theophylline   aminophylline       
 
         [0297]    Dnase (Pulmozyme) 
       Gastrointestinal System Disorders Gastro-Esophageal Reflux Disease (GERD) 
       [0298]    Peptic Ulcer Disease 
         [0299]    Inflammatory Bowel Disease 
         [0300]    Nausea and Vomiting 
         [0301]    Diarrhea, Constipation, Irritable Bowel Disease (IBD) 
         [0302]    Portal Hypertension and Cirrhosis 
         [0303]    Drug-Induced Liver Disease 
         [0304]    Pancreatitis 
         [0305]    Viral Hepatitis 
         [0306]    Liver Transplantation 
         [0307]    Histamine-2 receptor antagonists
       famotidine (Pepcid)   nizatidine (Axid)   pantoprazole (Protonix)   rabeprazole (Aciphex)   ranitidine (Zantac)       
 
         [0313]    Proton Pump Inhibitors (PPIs)
       esomeprazole (Nexium)   lansoprazole (Prevacid)   omeprazole (Prilosec)       
 
         [0317]    Anti-nausea/anti-vertigo medicaments
       anticholinergics
           antihistamines (Histamine-1 receptor antagonists)   
           dopamine antagonists   prokinetic gastric stimulant   serotonin 5HT 3  receptor antagonists
           dolasetron (Anzmet)   granisetron (Kytril)   ondansetron (Zofran)   
           other medicaments
           hydroxyzine (Atarax, Vistaril)   corticosteroids   benzodiazepines   cannabinoids   
               
 
         [0331]    Prokinetic gastric stimulants (gastric motility stimulants)
       cisapride (Propulsid))   metoclopramide (Reglan)       
 
         [0334]    Laxatives
       Saline laxatives
           magnesium salts   sodium salts   
           irritant/stimulant medicaments
           cascara   senna   phenolphthalein   bisacodyl   casanthranol   castor oil   
           bulk-producing medicaments
           methylcellulose   psyllium   polycarbophil   
           lubricant
           mineral oil   
           surfactants
           docusate   
           miscellaneous
           glycerin   lactulose   
               
 
         [0356]    Anti-diarrheal medicaments
       diphenoxylate   atropine   diphenoxin   loperamide   bismuth   lactobacillus       
 
         [0363]    Ulcerative Colitis Medicaments
       mesalamine   olsalazine       
 
       Renal System Disorders Acute Renal Failure 
       [0366]    Progressive Renal Failure/Chronic Renal Failure 
       Neurologic System Disorders Multiple Sclerosis and Inflammatory Polyneuropathies 
       [0367]    Epilepsy 
         [0368]    Parkinson&#39;s disease and Movement Disorders 
         [0369]    Pain management 
         [0370]    Headache 
         [0371]    Amyotrophic Lateral Sclerosis 
         [0372]    Anti-Epileptic Medicaments
       carbamazepine (Tegretol)   divalproex sodium (Depakote)   felbamate (Felbatol)   gabapentin (Neurontin)   lamotrigine (Lamictal)   oxcarbazepine (Trileptal)   phenytoin (Dilantin)   topiramate (Topamax)   zonisamide (Zonegran)       
 
         [0382]    Antimigraine Medicaments
       serotonin 5HT 1d  receptor agonists
           almotriptan (Axert)   frovatriptan (Frova)   naratriptan (Amerge)   rizatriptan (Rizalt)   sumatriptan (Imitrex)   zolmitriptan (Zomig)   
           ergot alkaloids
           dihydroergotamine (DHE)   
           isometheptine/dichlorophenazone (Midrin)   caffeine   pizotifen (Sanomigran)       
 
         [0395]    Sedative-Hypnotic Medicaments
       benzodiazepines
           alprazolam (Xanax)   clonazepam (Klonopin)   clorazepate (Tranxene)   diazepam (Valium)   flumazenil (Romazicon)-antagonist   lorazepam (Ativan)   midazolam (Versed)   triazolam (Halcion)   
           barbiturates/Anesthetics
           pentobarbital (Nembutal)   phenobarbital (Luminal)   thiopental (Pentothal)   
           non-depressant anxiolytic
           buspirone (BuSpar)   
               
 
         [0411]    Treatment of Alcoholism
       disulfiram (Antabuse)       
 
         [0413]    Pain Management Medicaments
       Opioids
           Opioid Peptides
               beta-endorphin   dynorphin
                   enkephalins   
                   
               Agonists
               codeine   etorphine   fentanyl (Sublimaze)   hydrocodeine   hydromorphone   meperidine (Demerol)   methadone (Dolophine)   morphine   oxycodone   propoxyphene   
               Agonist-antagonists
               buprenorphine   
               Partial Agonist
               dezocine (Dalgan)   nalbuphine (Nubain)   pentazocine (Talwain)   
               Antagonist
               naloxone (Narcan)   
               
           Non-opiate
           acetaminophen (tylenol)   tramadol (ultram)   
               
 
         [0441]    Anti-Parkinsonism Medicaments
       levodopa   carbidopa   bromocriptine (Parlodel)   pergolide (Permax)   amantadine (Symmetrel)   selegiline (Deprenyl)   anticholinergic agents   dopamine Agonists
           pramipexole (Mirapex)   ropinirole (Requip)   
           COMT inhibitors
           entacapone (Comtan)   tolcapone (Tasmar)   
               
 
         [0455]    Anti-Spasticity Medicaments
       baclofen (Lioresal)   botulinum toxin type A (Botox)   carisoprodol (Soma, Rela)   chlorphenesin (Maolate)   chlorzoxazone (Paraflex)   cyclobenzaprine (Flexeril)   dantrolene (Dantrium)   diazepam (Valium)   metaxalone (Skelaxin)   methocarbamol (Robaxin)   orphenadrine (Norflex)   tizanidine (Zanaflex)       
 
       Psychiatric System Disorders Childhood Psychiatric Disorders 
       [0468]    Attention Deficit Hyperactivity Disorder (ADHD)/Attention Deficit Disorder (ADD) 
         [0469]    Eating disorders 
         [0470]    Alzheimer&#39;s disease and Dementia Disorders 
         [0471]    Substance abuse and Addictive Disorders 
         [0472]    alcohol, tobacco and caffeine abuse 
         [0473]    Schizophrenia 
         [0474]    Depressive disorders 
         [0475]    Bipolar disorders 
         [0476]    Anxiety disorders 
         [0477]    Obsessive-Compulsive disorders 
         [0478]    Sleep disorders 
         [0479]    Psychostimulant Medicaments
       amphetamine mixed salts (Adderall)   dextroamphetamine (Dexedrine)   methylphenidate (Ritalin, Concerta)       
 
         [0483]    Antipsychotic Medicaments (Dopamine Antagonists)
       Phenothiazine type
           chlorpromazine (Thorazine)   fluphenazine (Prolixin)   
           Thioxanthene type
           thiothixene (Navane)   
           Butyrophenone type
           haloperidol (Haldol)   
           Dibenzodiazepine type
           clozapine (Clozaril)   
           Thienobenzodiazepine type
           olanzapine (Zyprexa)   quetiapine (Seroquel)   
               
 
         [0496]    Antidepressant Medicaments
       Tricyclic antidepressants (TCA&#39;s)
           amitriptyline (Elavil, Endep)   clomipramine (Anafranil), also a SSRI   desipramine (Norpramin)   doxepin (Sinequan)   imipramine (Tofranil)   maprotiline (Ludiomil)   nortriptyline (Aventyl, Pamelor)   protriptyline (Vivactil)   
           Monoamine oxidase inhibitors (MAO-I&#39;s)
           clorgyline (specific for MAO type A)   isocarboxazid (Marplan)   phenelzine (Nardil)   tranylcypromine (Parnate)   
           Second Generation Medicaments (not including SSRIs)
           amoxapine (Asendin)   bupropion (Wellbutrin)   nefazodone (Serzone)   trazodone (Desyrel)   
           Serotonin-Specific Reuptake Inhibitors (SSRIs)
           citalopram (Celexa)   clomipramine (Anafranil)   escitalopram (Lexapro)   fluoxetine (Prozac)   fluvoxamine (Luvox)   paroxetine (Paxil)   sertraline (Zoloft)   
           Other
           lithium   mirtazapine (Temeron)   venlafaxine (Effexor)   
               
 
         [0528]    Anti-Anxiety Agents
       barbiturates   benzodiazepines   buspirone (Buspar)   chloral hydrate   doxepin   hydroxyzine   sedative-hypnotics   serotonin reuptake inhibitors       
 
         [0537]    Anti-Demential Medicaments
       cholinesterase inhibitors
           donepezil (Aricept)   galantamine (Reminyl)   rivastigmine (Exelon)   tacrine (Cognex)   
               
 
       Endocrinologic System Disorders Diabetes Mellitus 
       [0543]    Thyroid disorders 
         [0544]    Adrenal Gland disorders 
         [0545]    Pituitary Gland disorders 
         [0546]    ACTH 
         [0547]    Adrenal androgens 
         [0548]    Adrenocortical Function Antagonists 
         [0549]    Mineralocorticoid antagonists 
         [0550]    Anti-Diabetic Medicaments
       Insulin   Sulfonylureas
           acetohexamide (Dymelor)   chlorpropamide (Diabinese)   glimepiride (Amaryl)   glipizide (Glucotrol)   glyburide (Micronase, DiaBeta)   tolazamide (Tolinase)   tolbutamide (Orinase)   
           Biguanides
           metformin (Glucophage)   
           Alpha-glucosidase Inhibitors
           acarbose (Precose)   miglitol (Glyset)   
           Thiazolidinedione Derivatives
           pioglitazone (Actos)   rosiglitazone (Avandia)   troglitazone (Rezulin)   
               
 
         [0569]    Thyroid Disorder Medicaments
       Levothyroxine   Liothyronine   Liotrix       
 
         [0573]    Hypothalamic and Pituitary Gland Medicaments
       bromocriptine (Parlodel)   chorionic gonadotropin (hCG)   corticotropin generic (ACTH)   cosyntropin (Cortrosyn)   desmopressin (DDAVP)   gonadorelin acetate (GnRH) (Lutrepulse)   gonadorelin hydrochloride (GnRH) (Factrel)   goserelin acetate (Zoladex)   growth hormone   histrelin (Supprelin)   leuprolide (Lupron)   menotropins (hMG) (Pergonal, Humegon)   nafarelin (Synarel)   octreotide (Sandostatin)   oxytocin (Pitocinit, Syntocinon)   pergolide (Permax)   protirelin (Thypinone, Relefact TRH)   sermorelin (GHRH) (Geref)   somatrem (Protropin)   somatropin (Humatrope, Nutropin)   thyrotropin (TSH) (Thytropar)   urofollitropin (Metrodin)   vasopressin (Pitressin Synthetic)       
 
       Gynecologic System and Obstetric Conditions Pregnancy and Lactation 
       [0597]    Infertility 
         [0598]    Contraception 
         [0599]    Menstruation-related disorders 
         [0600]    Endometriosis 
         [0601]    Hormone Replacement Therapy (HRT) 
         [0602]    Conjugated estrogens (Premarin) 
         [0603]    desogestrel 
         [0604]    di-norgestrel 
         [0605]    ethinyl diacetate 
         [0606]    ethinyl estradiol 
         [0607]    levonorgestrel 
         [0608]    medroxyprogesterone 
         [0609]    norethindrone 
         [0610]    norgestimate 
         [0611]    progesterone 
       Urologic System Disorders Erectile Dysfunction 
       [0612]    Benign Prostatic Hypertrophy 
         [0613]    Urinary Incontinence 
         [0614]    apomorphine 
         [0615]    alprostadil 
         [0616]    phosphodiesterase (PDE-5) inhibitors
       sildenafil (Viagra)   tadalafil (Cialis)   vardenafil (Levitra)   tolterodine (Detrol)   tamulosin (Flomax)   yohimbine       
 
       Immunologic System Disorders Systemic Lupus Erythematosus and Other Collagen-Vascular Diseases 
       [0623]    Allergic and pseudo-allergic drug reactions 
         [0000]    Bone and Joint System Disorders Osteoporosis and osteomalacia 
         [0624]    Rheumatoid Arthritis 
         [0625]    Osteoarthritis 
         [0626]    Gout and hyperuricemia 
         [0627]    Medicaments Used in the Control of Inflammation
       Non-steroidal anti-inflammatory drugs (NSAIDs)
           aspirin   diclofenac (Cataflam, Voltaren)   diflusnisal (Dolobid)   etodolac (Lodine)   fenoprofen (Nalfon)   flubiprofen (Ansaid)   ibuprofen (Motrin, Advil, Nuprin)   indomethacin (Indocin)   ketoprofen (Orudis)   ketorolac (Toradol)   meclofenamate   nabumetone (Relafen)   naproxen (Naprosyn)   oxaprozin (Daypro)   phenylbutazone   piroxicam (Feldene)   salicylate   sulindac (Clinoril)   tolmetin (Tolectin)   
           Cyclooxygenase-2 inhibitors (COX-2)
           celecoxib (Celebrex)   rofecoxib (Vioxx)   
               
 
         [0651]    Arthritis and Gout Medicaments
       allopurinol   anti-malarial compounds
           chloroquine   
           colchicine   enbrel   Glucocorticoids   Gold   methotrexate   NSAIDs   Penicillamine       
 
         [0662]    Other Medicaments
       alendronate (Fosamax)   raloxifene (Evista)       
 
       Disorders of the Eyes, Ears, Nose, and Throat Systems Glaucoma Allergic Rhinitis 
       [0665]    Histamine-1 receptor antagonists
       brompheniramine (Dimetane)   cetirizine (Zyrtec)   chlorpheniramine (Chlor-Trimeton)   clemastine (Tavist)   cyproheptadine (Periactin)   dimenhydrinate (Dramamine)   diphenhydramine (Bendaryl)   doxylamine (Sominex, Unisom)   fexofenadine (Allegra)   loratidine (Claritin)       
 
         [0676]    Sympathomimetic medicaments
       pseudoephedrine (Sudafed)       
 
       Dermatologic System Disorders Acne 
       [0678]    Psoriasis 
         [0679]    Rosacea and pigmentation disorders 
         [0680]    Drug-Induced skin reactions 
       Hematologic System Disorders Hematopoeisis 
       [0681]    Anemias 
         [0682]    Coagulation disorders 
         [0683]    Sickle-cell anemia 
         [0684]    Drug-induced hematologic disorders 
         [0685]    Coagulation Disorders Medicaments
       aspirin   clopidogrel (Plavix)   fibrinolytic inhibitors   fibrinolytics   glycoprotein (GP) IIb/IIIa antagonists/monoclonal antibodies
           abciximab (Reopro)   eptifibatide (Integrelin)   tiofibran (Aggrastat)   
           heparin   low-molecular weight heparins   Plasma fractions—blood factors   ticlopidine (Ticlid)   vitamin K   warfarin (Coumadin)       
 
       Infectious System Diseases Central Nervous System (CNS) Infections 
       [0700]    Lower Respiratory Tract Infections 
         [0701]    Upper Respiratory Tract Infections 
         [0702]    Skin and Soft Tissue Infections 
         [0703]    Infective Endocarditis 
         [0704]    Tuberculosis 
         [0705]    Gastrointestinal Infections and Enterotoxigenic poisonings 
         [0706]    Intra-abdominal Infections 
         [0707]    Parasitic diseases 
         [0708]    Urinary Tract Infections and Prostatis 
         [0709]    Sexually Transmitted Diseases 
         [0710]    Bone and Joint Infections 
         [0711]    Sepsis and Septic Shock 
         [0712]    Superficial Fungal Infections 
         [0713]    Invasive Fungal Infections 
         [0714]    Infections in Immunocompromised Patients 
         [0715]    Antimicrobial prophylaxis in Surgery 
         [0716]    Vaccines, toxoids, and other immunobiologics 
         [0717]    Human Immunodeficiency Virus Infection 
         [0718]    Medicaments Used in Infectious Diseases 
         [0719]    Cell Wall Synthesis Inhibitors
       Penicillins
           amoxicillin (Amoxil Polymox)   ampicillin (Principen, Omnipen)   benzathine Penicillin G   benzyl Penicillin (Penicillin G)   carbenicillin (Geocillin)   cloxacillin (Cloxapen)   dicloxacillin (Dynapen)   methicillin (Staphcillin)   mezlocillin   nafcillin (Nafcil, Unipen)   oxacillin   phenoxymethyl Penicillin (Penicillin V)   piperacillin (Pipracil)   ticarcillin (Ticar)   
           Cephalosporins
           1st generation:
               cefazolin (Ancef, Defzol)   cephalexin (Keflex)   cephalothin (Keflin)   
               2nd generation:
               cefaclor (Ceclor)   cefoxitin (Mefoxin)   cefpodoxime (Vantin)   cefuroxime (Zinacef, Ceftin)   loracarbef (Lorabid)   
               3rd generation:
               cefoperazone   cefotaxime (Claforan)   cefotetan   ceftazidime (Fortax, Taxidime, Tazicef)   ceftriaxone (Rocephin)   veftizoxime (Cefizox)   
               4th generation:
               cefepime   
               
           Other beta-Lactams aztreonam (Azactan)
           clavulanic acid   imipenem (Primaxin)   meropenem (Merrem IV)   sulbactam   
           Other Cell-Wall Synthesis Inhibitors
           bacitracin   
           cycloserine   fosfomycin (Monurol)
           vancomycin (Vancocin)   
               
 
         [0765]    Agents Which Affect Cell Membranes
       Polymixins
           Colistimethate   Polymyxin B   
               
 
         [0769]    Protein Synthesis Inhibitors
       Aminoglycosides
           amikacin (Amikin)   gentamicin (Garamycin)   kanamycin (Kantrex)   neomycin   netilmicin (Netromycin)   streptomycin   tobramycin   
           Tetracyclines
           demeclocycline (Declomycin)   doxycycline   doxycycline (Vibramycin, Doryx)   tetracycline (Achromycin)   
           Macrolides
           azithromycin (Zithromax)   clarithromycin (Biaxin)   erythromycin esters   erythromycin   
           Other Protein Synthesis Inhibitors
           Chloramphenicol (Chloromycetin)   Clindamycin (Cleocin)   Spectinomycin (Trobicin)   
               
 
         [0792]    Inhibitors of Folate-Dependent Pathways
       co-trimoxazole   silver Sulfadiazine   sodium Sulfacetamide   sulfamethoxazole (Gantanol)   sulfasalazine (Azulfidine) (Salicylazosulfapyridine)   sulfisoxazole (Gantrisin)   sulfonamides       
 
         [0800]    Dihydrofolate Reductase Inhibitor
       trimethoprim       
 
         [0802]    DNA Gyrase Inhibitors
       ciprofloxacin (Cipro)   gatifloxacin (Tequin)   levofloxacin (Levaquin)   lomefloxacin (Maxaquin)   nalidixic acid   ofloxacin (Floxin)       
 
         [0809]    Urinary Tract Antiseptics
       nitrofurantoin       
 
         [0811]    Antimyobacterial Agents
       First-line anti-TB medicaments
           ethambutol   isoniazid (INH)   pyrazinamide   rifampin (Rimactane)   streptomycin   
           Second-line anti-TB medicaments
           capreomycinA   cycloserine   dapsone   ethionamide   para-aminosalicylic acid   
               
 
         [0824]    AntiFungal Agents
       amphotericin B (Fungizone, Amphotec)   clotrimazole (Mycelex)   fluconazole (Diflucan)   flucytosine   griseofulvin   itraconazole (Sporanox)   ketoconazole (Nizoral)   miconazole (Monistat)   nystatin (Mycostatin)       
 
         [0834]    AntiParasitic Agents 
         [0835]    Antimalarials
       chloroquine (Aralen)   mefloquine (Lariam)   primaquine   pyrimethamine-sulfadoxine (Fansidar)       
 
         [0840]    Antiprotozoals
       metronidazole (Flagyl)   pentamidine isethionate   pyrimethamine-sulfonamide   trimethoprim (generic) sulfamethoxazole (Gantanol)       
 
         [0845]    Antihelminthic Medicaments
       mebendazole   praziquantel (Biltricide)   pyrantel pamoate   thiabendazole (Mintezol)       
 
         [0850]    Antiviral Medicaments
       acyclovir (Zovirax)   didanosine (DDI)   foscarnet (Foscavir)   ganciclovir (DHPG, Cytovene)   ribavirin   rimantadine   stavudine (d4T))   valacyclovir (Valtrex)   vidarabine (Vira-A)   zalcitabine (ddC)   zidovudine (Azidothymidine, AZT)       
 
         [0862]    Protease inhibitors
       indinavir (Crixivan)   ritonavir (Norvir)   saquinavir (Fortovase)       
 
       Oncologic and Immunological Disorders Breast Cancer 
       [0866]    Lung Cancer 
         [0867]    Colorectal Cancer 
         [0868]    Prostate Cancer 
         [0869]    Malignant Lymphomas 
         [0870]    Ovarian Cancer 
         [0871]    Acute Leukemias 
         [0872]    Chronic Leukemias 
         [0873]    Melanoma and other Skin Cancers 
         [0874]    Hematopoeitic Stem Cell Transplantation 
         [0875]    Anti-Neoplastic Medicaments
       Alkylating Agents
           busulfan (Myleran)   carboplatin (Paraplatin)   carmustine (BNCU, BiCNU)   cisplatin (Platinol)   cyclophosphamide (Cytoxan)   ifofamide (Ifex)   lomustine (CCNU, CeeNU)   mechlorethamine (Mustargen)   melphalan (Alkeran)   procarbazine (Matulane)   thiotepa   
           Antimetabolites
           folic acid Antagonist   methotrexate   
           Purine Antagonists 6-mercaptopurine
           6-thioguanine   
           Pyrimidine Antagonists
           cytarabine (ARA-C)   fluorouracil (5-FU)   
           Hormonal Agents Hormones
           diethylstilbestrol (DES)   estrogens   prednisone (Deltas one)   
           Modulation of Hormone Release &amp; Action Aminoglutethimide
           leuprolide acetate   tamoxifen (Nolvadex)   
           Plant Alkaloids
           Vinca Alkaloids
               vinblastine (Velban)   vincristine (Oncovin)   
               Podophyllotoxins
               etoposide (VP-16)   
               Other
               docetaxel (Taxotere)   paclitaxel (Taxol)   
               
           Antibiotics
           bleomycin (Blenoxane)   dactinomycin (Cosmegen)   daunorubicin (DaunoXome)   doxorubicin (Adriamycin)   mitomycin (Mutamycin)   
           Other Anti-neoplastic Medicaments
           amsacrine (AMSA)   azathioprine (Imuran)   capecitabine (Xeloda)   chlorambucil (Leukeran)   cyclosporine (Sandimmune, Neoral)   gemcitabine (Gemzar)   hydroxyurea (Hydrea)   mitotane (Sodren)   mitoxantrone (Novantrone)   pamidronate (Aredia)   
               
 
         [0929]    Immunosuppressant Medicaments
       15-desoxyspergualin   corticosteroids   cyclosporine   Interferons   Interleukins   mycophenolate mofetil   sirolimus (rapamycin)   tacrolimus   thalidomide       
 
       Nutritional Disorders 
       [0939]    Malnutrition, vitamin and mineral deficiencies 
         [0940]    Enteral Nutrition 
         [0941]    Obesity
       orlistat (Xenical)   appetite suppressants
           sympathomimetic stimulants   amphetamine stimulants   
               
 
         [0946]    Mineral supplementation
       calcium ion   iodine   iron   magnesium ion   phosphorous   potassium ion   selenium   sodium ion   zinc       
 
         [0956]    Fat-soluble vitamins
       vitamin A   vitamin D   vitamin E
           vitamin K   
               
 
         [0961]    Water-soluble vitamins
       vitamin C   thiamine (vitamin B1)   riboflavin (vitamin B2)   niacin (vitamin B3)   pyridoxine (vitamin B6)   folate   cyanocobalamin (vitamin B12)       
 
       Medicaments Used to Alleviate Symptoms of Allergic Rhinitis, Upper Respiratory Symptoms, Cough, Mild Aches and Pains 
       [0969]    Nasal Decongestants
       ephedrine   phenylephrine   phenylpropanolamine   pseudoephedrine       
 
         [0974]    Antihistamines (Histamine-1 receptor antagonists) 
         [0975]    Antitussive agents
       benzonatate   codeine   dextromethorphan       
 
         [0979]    Expectorants
       guaifenesin   iodinated glycerol   terpinhydrate       
 
         [0983]    Xanthines
       aminophylline   caffeine   dyphylline   theophylline       
 
         [0988]    Pain relievers
       narcotic agonists   NSAIDS   acetaminophen       
 
       Dietary Supplements 
       [0992]    Arnica 
       Other Drugs 
       [0993]    abacavir sulfate
 
acetazolamide
 
acetylsalicylic acid
 
albendazole
 
allopurinol
 
amiloride hydrochloride
 
amitriptyline hydrochloride artemether
 
atropine sulfate
 
benznidazole
 
biperiden hydrochloride
 
chloroquine phosphate
 
chlorpheniramine maleate
 
chlorpromazine hydrochloride
 
cimetidine
 
ciprofloxacin hydrochloride
 
clofazimine
 
clomiphene citrate
 
clomipramine hydrochloride
 
cloxacillin sodium
 
codeine phosphate
 
dapsone
 
didanosine
 
diethylcarbamazine citrate
 
digoxin
 
diloxanide furoate
 
       DL-methionine 
     Doxycycline 
     Efavirenz 
       [0994]    ergometrine maleate
 
ergotamine tartrate
 
erythromycin ethyl succinate
 
ethambutol hydrochloride
 
ethosuximide
 
ferrous sulfate
 
alendronate sodium
 
amlodipine besylate
 
amphetamine (mixed salts)
 
atorvastatin calcium
 
benazepril hydrochloride
 
bisoprolol fumarate
 
bupropion hydrochloride
 
carbidopa
 
cefprozil
 
cetirizine hydrochloride
 
citalopram hydrobromide
 
clindamycin hydrochloride
 
clonidine hydrochloride
 
clopidogrel bisulfate
 
cyclobenzaprine hydrochloride
 
desloratadine
 
digoxin
 
diltiazem hydrochloride
 
doxazosin mesylate
 
doxycycline
 
enalapril maleate
 
fexofenadine hydrochloride
 
fluoxetine hydrochloride
 
folic acid
 
fosinopril sodium
 
hydrocodone bitartrate
 
hydrocodone
 
hydroxyzine hydrochloride
 
indinavir
 
irbesartan
 
isosorbide mononitrate
 
lamivudine
 
levothyroxine sodium
 
lopinavir
 
loratadine
 
losartan potassium
 
meclizine hydrochloride
 
medroxyprogesterone acetate
 
meperidine
 
metformin hydrochloride
 
methylphenidate hydrochloride
 
methylprednisolone
 
metoclopramide hydrochloride)
 
minocycline hydrochloride
 
montelukast sodium
 
naproxen sodium
 
nelfinavir
 
nevirapine
 
niclosamide
 
nicotinamide
 
nifurtimox
 
nitrofurantoin
 
nortriptyline hydrochloride
 
oxybutynin chloride
 
oxycodone hydrochloride
 
paracetamol
 
paroxetine hydrochloride
 
penicillin V potassium
 
phenytoin sodium
 
pioglitazone hydrochloride
 
prednisolone
 
primaquine phosphate
 
pravastatin sodium
 
prednisolone
 
promethazine hydrochloride
 
promethazine fumarate
 
propylthiouracil
 
pyrantel embonate
 
pyridostigmine bromide
 
raloxifene hydrochloride
 
ranitidine hydrochloride
 
rifampicin
 
risedronate sodium
 
risperidone
 
rosiglitazone maleate
 
salbutamol sulfate
 
saquinavir mesylate
 
sertraline hydrochloride
 
sildenafil citrate
 
sulfadiazine
 
sumatriptan succinate
 
tamoxifen citrate
 
tamsulosin hydrochloride
 
temazepam
 
terazosin hydrochloride
 
timolol maleate
 
tolterodine tartrate
 
tramadol hydrochloride
 
trazodone hydrochloride
 
triclabendazole
 
valacyclovir hydrochloride
 
valdecoxib
 
valproic acid
 
valsartan
 
venlafaxine hydrochloride
 
verapamil hydrochloride
 
warfarin sodium
 
zolpidem tartrate
 
         [0995]    Bilberry 
         [0996]    Black Cohosh 
         [0997]    Cat&#39;s claw 
         [0998]    Chamomile 
         [0999]    Echinacea 
         [1000]    Evening Primrose Oil 
         [1001]    Fenugreek 
         [1002]    Flaxseed 
         [1003]    Feverfew 
         [1004]    Garlic 
         [1005]    Ginger root 
         [1006]    Ginko biloba 
         [1007]    Ginseng 
         [1008]    Goldenrod 
         [1009]    Hawthorn 
         [1010]    Kava-Kava 
         [1011]    Licorice 
         [1012]    Milk thistle 
         [1013]    Psyllium 
         [1014]    Rauwolfia 
         [1015]    Senna 
         [1016]    Soybean 
         [1017]    St. John&#39;s wort 
         [1018]    Saw palmetto 
         [1019]    Turmeric 
         [1020]    Valerian 
         [0000]    Therapeutic Proteins and Biotechnology Medicaments