Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2000-11-21
2002-12-17
Azpuru, Carlos (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S045000, C424S046000, C424S434000, C424S435000, C424S443000, C424S449000, C424S451000, C424S464000
Reexamination Certificate
active
06495154
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to methods and pharmaceutical compositions for treating sexual dysfunction; more particularly, the invention relates to treatment of premature ejaculation, preferably by on demand administration of clomipramine or a pharmacologically acceptable acid addition salt thereof.
BACKGROUND
Premature ejaculation is a debilitating sexual dysfunction. This dysfunction can lead to an inability to enter or sustain relationships and can cause psychological damage to sufferers. Premature ejaculation can also impair reproductive success.
Previous methods of treating premature ejaculation included psychological therapies, topical anesthetics and the use of devices (U.S. Pat. Nos. 5,535,758, 5,063,915, 5,327,910, and 5,468,212). All of these methods have significant drawbacks. Psychological therapies benefit only a subset of patients and require specialized therapists who may not be available to all patients, particularly in remote areas. Furthermore, psychological therapies cannot alleviate premature ejaculation resulting from non-psychological causes. Anesthetic agents decrease sensitivity of tissues, thereby diminishing sexual pleasure. Also, topical anesthetics can be transferred to sexual partners and thereby decrease their sensitivity and pleasure as well. With regard to devices, these can be awkward, inconvenient and embarrassing to use. Devices are highly conspicuous, and reveal the very condition which the suffering partner may prefer to conceal. Additionally, devices can cause irritation to one or both partners.
Methods for treating premature ejaculation by systemic administration of several different pharmacologically active compounds have been described (U.S. Pat. Nos. 4,507,323, 4,940,731, 5,151,448, 5,276,042 and 5,707,999; PCT Publication No. WO 95/13072). However, these drugs may not be effective for all patients, and the side effects of these drugs can halt treatment or impair patient compliance. Disease states or adverse interactions with other drugs may contraindicate the use of these compounds or require lower dosages that may not be effective to delay the onset of ejaculation. In addition, many drugs must be administered chronically or at times that are inconvenient.
Oral administration of the antidepressant fluoxetine has been claimed to treat premature ejaculation. However, the administration of fluoxetine has many undesired aspects. U.S. Pat. No. 5,151,448 describes administration of fluoxetine on a daily basis which, according to many clinicians, presents a compliance issue as patients often miss or forget to take their dose. In addition, patients with hepatic or renal impairments may not be able to use fluoxetine due to its metabolism in the liver and excretion via the kidney. Systemic events during oral fluoxetine treatment involving the lungs, kidneys or liver have occurred, and death has occurred from overdoses. In addition, side effects of oral fluoxetine administration include hair loss, nausea, vomiting, dyspepsia, diarrhea, anorexia, anxiety, nervousness, insomnia, drowsiness, fatigue, headache, tremor, dizziness, convulsions, sweating, pruritis and skin rashes. Fluoxetine interacts with a range of drugs, often by impairing their metabolism by the liver.
U.S. Pat. No. 4,940,731 describes the oral or parenteral administration of sertraline on a daily basis for treating premature ejaculation. It has been recognized that sertraline shares many of the same problems as fluoxetine; see Martindale,
The Extra Pharmacopoeia,
31st edition, at p. 333 (London: The Royal Pharmaceutical Society, 1996). Sertraline is metabolized in the liver, and is excreted in the urine and feces. Thus, patients with cirrhosis must take lower doses, and caution must be exercised when administering sertraline to patients with renal impairment. Individuals taking monoamine oxidase inhibitors cannot take sertraline due to the risk of toxicity, leading to memory changes, confusion, irritability, chills, pyrexia and muscle rigidity. Side effects resulting from oral sertraline administration include nausea, diarrhea, dyspepsia, insomnia, somnolence, sweating, dry mouth, tremor and mania. Rare instances of coma, convulsions, fecal incontinence and gynecomastia have occurred in patients undergoing sertraline therapy.
U.S. Pat. No. 5,276,042 describes daily administration of paroxetine for the treatment of premature ejaculation. Paroxetine is predominantly excreted in the urine, and decreased doses are recommended in patients with hepatic and renal impairments. Like sertraline, paroxetine cannot be given to patients undergoing treatment with a monoamine oxidase inhibitor. Side effects from oral administration of paroxetine include hyponatremia, asthenia, sweating, nausea, decreased appetite, oropharynx disorder, somnolence, dizziness, insomnia, tremor, anxiety, impaired micturition, weakness and paresthesia.
Administration of the &agr;
1
-adrenergic blockers has been described to treat psychogenic premature ejaculation. U.S. Pat. No. 5,707,999 describes daily administration of alfuzosine or terazosine. A common side effect of these drugs is postural hypotension. In addition, daily administration increases the possibility of patients suffering from a drug×s undesirable side effects as a result of continuous exposure to the agent.
Oral administration of clomipramine to treat men suffering from premature ejaculation has been described in Strassberg et al. (1999)
J. Sex Marital Ther.
25(2):89-101. The reference describes “as needed” oral administration “as little as four hours prior to sexual activity.” Such a dosing regimen, however, still fails to provide for a flexible and convenient method for treating premature ejaculation.
Thus there is a need for methods and dosage forms for treating premature ejaculation that requires no specialized psychological therapy, can be used conveniently and without embarrassment, and avoids the disadvantages associated with prior therapeutic methods and dosage forms.
SUMMARY OF THE INVENTION
Accordingly, it is a primary object of the invention to address the above-described need in the art by providing a novel method for delaying the onset of ejaculation by systemically administering on demand a pharmaceutical formulation containing an amount of an active agent selected from the group consisting of clomipramine and pharmacologically acceptable acid addition salts thereof effective to delay the onset of ejaculation by the individual during sexual activity.
It is another object of the invention to provide such a method wherein the pharmaceutical formulation is administered less than four hours prior to engaging in sexual activity.
It is a further object of the invention to provide such a method wherein the individual suffers from premature ejaculation.
It is yet a further object of the invention to provide such a method wherein the pharmaceutical formulation is administered orally.
It is another object of the invention to provide such a method wherein the pharmaceutical formulation is administered buccally.
It is a further object of the invention to provide such a method wherein the pharmaceutical formulation is administered transmucosally.
It is still a further object of the invention to provide such a method wherein the pharmaceutical formulation is administered nasally.
It is another object of the invention to provide a dosage form for delaying the onset of ejaculation in a male individual, comprising a rapid-release formulation for systemic absorption containing an amount of an active agent selected from the group consisting of clomipramine and pharmacologically acceptable acid addition salts thereof effective to delay the onset of ejaculation by the individual during sexual activity.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention.
In a first aspect of the invention, a method is provided fo
Gesundheit Neil
Tam Peter
Wilson Leland F.
Azpuru Carlos
Reed Dianne E.
Reed & Associates
Vivus Inc.
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