Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Reexamination Certificate
2001-03-29
2004-08-03
Hartley, Michael G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
C424S043000, C424S400000, C514S619000, C514S397000, C514S471000, C128S200140
Reexamination Certificate
active
06770262
ABSTRACT:
1. FIELD OF THE INVENTION
The present invention is directed to a method for treating gastroparesis. More particularly, the present invention is directed to a method for treating gastroparesis typically caused by diabetes mellitus (including type 1 and type 2 diabetes), postviral syndromes, anorexia nervosa, malnutrition, alcoholism, surgery on the stomach or vagus nerve, medications, particularly anticholinergics and narcotics which slow contractions in the intestine, gastroesophageal reflux disease, smooth muscle disorders such as amyloidosis and scleroderma, nervous system diseases (including abdominal migraine and Parkinson's disease), or metabolic disorders (including hypothyroidism) with the nasal administration of metoclopramide.
2. BACKGROUND OF THE INVENTION
The vagus nerve controls the movement of food through the digestive tract. Normally, stomach muscles contract about three times a minute and the stomach empties within 90-120 minutes after eating. When the vagus nerve is damaged or dysfunctional, stomach muscles do not work properly and the stomach contraction becomes sluggish and/or less frequent. As a result, the movement of food is slowed or stopped. Gastroparesis is the medical term for this condition.
Typical symptoms of gastroparesis are nausea, vomiting, early satiety, weight loss, abdominal bloating, abdominal discomfort, epigastric pain, anorexia. These symptoms may be mild or severe. In addition, since food lingers too long in the stomach, gastroparesis can lead to complications such as bacterial overgrowth from the fermentation of food, hardening of food into solid masses which are called bezoars that may cause nausea, vomiting, and obstruction in the stomach. Bezoars can be dangerous if they block the passage of food into the small intestine.
Major causes of gastroparesis include diabetes, postviral syndromes, anorexia nervosa, surgery on the stomach or vagus nerve, medications, particularly anticholinergics and narcotics (drugs that slow contractions in the intestine), gastroesophageal reflux diseases, smooth muscle disorders such as amyloidosis and scleroderma, nervous system diseases such as abdominal migraine and Parkinson's disease, and metabolic disorders such as hypothyroidism.
As stated above, diabetes is a major cause of gastroparesis. Blood glucose levels of diabetic patients often remain high over a long period of time. High blood glucose causes chemical changes in nerves and damages the blood vessels that carry oxygen and nutrients to the magus nerves. As a result, at least 20 percent of people with type 1 diabetes develop gastroparesis. Gastroparesis also occurs in people with type 2 diabetes, although less often.
Metoclopramide in oral and injectable forms, cisapride, erythromycin, and domperidone have been investigated for the treatment of gastroparesis. Metoclopramide (MCP) stimulates stomach muscle contractions to help empty food. It also helps reduce nausea and vomiting. Metoclopramide is taken 20 to 30 minutes before meals and at bedtime. Traditionally, treatment of gastroparesis is via injection or oral route. Metoclopramide is currently available in a tablet form, injection form, and syrup form under the name Reglan® (A.H. Robbins Company). The injection form has an onset of action of about 1-3 minutes after intravenous administration and an onset of action of about 10-15 minutes after intramuscular administration. However, injections, particularly daily multiple injections, are often very painful and inconvenient. Intravenous administration often requires a hospital setting. As a result, compliance (compliance=following dosage regimen prescribed) is often very poor. Metoclopramide in the tablet or syrup form can be effectively and rapidly absorbed through the GI tract by healthy persons. Pharmacokinetics studies of subjects show that oral bioavailability of metoclopramide is approximately 80%±15.5%. Peak plasma concentrations occur at about 1-2 hours after a single oral dose. However, for patients with gastroparesis, metoclopramide absorption through the GI tract is unpredictable and far less effective, with predictability and effectiveness having an inverse relationship to the severity of the symptom, i.e., the more severe the symptoms, the less likely that oral administration is an option. Further complicating the matter of oral administration of metoclopramide is the fact that patients with gastroparesis often have symptoms such as vomiting and nausea. If vomiting takes place, the amount of metoclopramide that remains in the stomach is unknown, and the result of treatment is even less predictable.
Side effects of metoclopramide include fatigue, sleepiness, depression, anxiety, and difficulty with physical movement. Mental depression has occurred in patients with and without prior history of depression. Symptoms range from mild to severe, including suicidal ideation and suicide. Other symptoms such as involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, and dystonic reactions such as stridor and dyspnea.
These side effects may interfere with patient compliance with the drug regimen prescribed, as well as interfere with the patient's ability to effectively communicate the nature and severity of this and other side effects. Poor compliance or non-compliance is observed in about 25% of patients with an oral medication regimen. Due to nausea and vomiting associated with gastroparesis, patients are even more reluctant to comply with the oral regimen.
U.S. Pat. No. 4,624,965 (hereinafter Wenig) discusses nasal administration of MCP. No experience with human subjects using a nasal spray formulation of MCP (MCP ns) is disclosed within Wenig. Furthermore, Wenig did not disclose using any forms of MCP, or any particular regimen for the purpose of treating gastroparesis.
U.S. Pat. No. 5,760,086 to Psilogenis (hereinafter Psilogenis) is solely directed to nasal administration of MCP for the treatment of a specific disease state known as delayed onset emesis, particularly emesis induced by chemotherapy. Psilogenis did not disclose nasal administration of MCP for the purpose of treating gastroparesis.
In view of the above, there is a clear need for an improved method of treating gastroparesis. Specifically, there is a need to develop an improved method of administering metoclopramide. More specifically, there is a need to develop an improved method of administering metoclopramide safely, effectively, and consistently.
3. SUMMARY OF THE INVENTION
The present invention is directed to providing a method for treating gastroparesis by using a dosage form of MCP that avoids or reduces the incidence of patient non-compliance. Another object of the present invention is to provide a method for treating gastroparesis by nasally administering MCP which avoids or reduces the incidence of side-effects experienced by patients.
Yet another Object of the present invention is to provide a method for treating gastroparesis caused by diabetes by using a dosage form of MCP that avoids or reduces the problem of patient non-compliance.
It is still another object of the present invention to provide a method for treating gastroparesis caused by type 1 or type 2 diabetes by using a dosage form of MCP that avoids or reduces the problem of patient non-compliance.
It is yet still another object of the present invention to provide a method for sufficiently treating gastroparesis caused by diabetes using a dosage form of MCP that avoids or reduces the incidence of side-effects experienced by patients.
It is even yet still another object of the present invention to provide a method for sufficiently treating gastroparesis caused by type 1 or type 2 diabetes using MCP nasal spray that avoids or reduces the severity of side-effects experienced by patients.
It is further an object of the present invention to provide a method for sufficiently controlling gastroparesis caused by diabetes by nasally administering MCP that avoids or reduces the problems assoc
Lehman Laura S.
Oliver Ruth
Petrone Michael
Retzios Anastassios D.
Tierney David
Haghighatian Mina
Hartley Michael G.
Jones Day
Questcor Pharmaceuticals, Inc.
LandOfFree
Nasal administration of agents for the treatment of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nasal administration of agents for the treatment of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nasal administration of agents for the treatment of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3339492