Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-07-12
2002-01-29
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S434000, C424S435000, C424S484000, C424S485000, C424S486000, C424S489000, C514S179000, C514S282000, C514S284000, C514S289000
Reexamination Certificate
active
06342246
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to dosage forms and methods for ameliorating erectile dysfunction in male patients. More particularly, this invention relates to the use of fast-dispersing dosage forms of drugs for amelioration of erectile dysfunction in male patients.
BACKGROUND OF THE INVENTION
A normal erection occurs as a result of a coordinated vascular event in the penis. This is usually triggered neurally and consists of vasodilatation and smooth muscle relaxation in the penis and its supplying arterial vessels. Arterial inflow causes enlargement of the substance of the corpora cavernosa. Venous outflow is trapped by this enlargement, permitting sustained high blood pressures in the penis sufficient to cause rigidity. Muscles in the perineum also assist in creating and maintaining penile rigidity. Erection may be induced centrally in the nervous system by sexual thoughts or fantasy, and is usually reinforced locally by reflex mechanisms.
Male erectile dysfunction (MED) is defined as the inability to achieve and sustain an erection sufficient for intercourse. In any given case this can result from psychological disturbances (psychogenic), from physiological abnormalities in general (organic), from neurological disturbances (neurogenic), hormonal deficiencies (endocrine) or from a combination of the foregoing.
The effect of apomorphine on penile tumescence in male patients has been studied. These studies show that while apomorphine can indeed induce an erection in a psychogenic male patient, the apomorphine dose required to achieve a significant erectile response is usually accompanied by nausea or other serious undesirable side effects such as hypertension, flushing and diaphoresis. The specific mechanisms by which apomorphine acts to produce an erectile response in a human patient are not yet completely understood, however.
Moreover, apomorphine has been shown to have very poor oral bioavailability. See, for example, Baldessarini et al., in Gessa et al., eds.,
Apomorphine and Other Dopaminomimetics, Basic Pharmacology,
Vol. 1, Raven Press, N.Y. (1981), pp. 219-228.
WO95/28930 discloses sublingual apomorphine dosage forms, usually containing about 2.5 to about 10 milligrams of apomorphine, and dissolving in water within a time period of at least about 2 minutes but less than about 10 minutes, preferably about 3 minutes to about 5 minutes, have been found to be effective in male patients suffering from psychogenic erectile dysfunction for the induction and maintenance of an erection sufficient for intercourse (i.e. vaginal penetration) without nausea or other undesirable side effects. The apomorphine is administered sublingually, preferably about 15 to 20 minutes prior to sexual activity, and so as to maintain a predetermined circulating serum levels and mid-brain tissue levels of apomorphine during the period of sexual activity.
The foregoing sublingual apomorphine dosage forms are also suitable for screening patients complaining of erectile dysfunction so as to identify patients of psychogenic etiology.
PCT/GB96/02020 discloses a pharmaceutical composition for oral administration comprising a carrier and, as active ingredient, a dopamine agonist, in which the composition is in the form of a fast-dispersing dosage form designed to release the active ingredient rapidly in the oral cavity.
It was found that such fast-dispersing dosage forms promote pre-gastric absorption of the active ingredient, that is, absorption of the active ingredient from that part of the alimentary canal prior to the stomach. The term “pre-gastric absorption” thus includes buccal, sublingual, oropharyngeal and oesophageal absorption. Dopamine agonists absorbed by such pre-gastric absorption pass straight into the systemic circulatory system thereby avoiding first pass metabolism in the liver. Accordingly, bioavailability of dopamine agonists absorbed in this way may also be increased. This means that the dose of such dopamine agonists may be reduced whilst still producing the desired beneficial effects and this decrease in dose will result in a corresponding reduction of unwanted side effects.
The pharmaceutical compositions disclosed in PCT/GB96/02020 were developed for the treatment and/or evaluation of Parkinson's disease.
SUMMARY OF THE INVENTION
It has now been found that fast-dispersing dosage forms containing a dopamine agonist, such as apomorphine, may be used to treat male erectile dysfunction.
According to the present invention there is provided a pharmaceutical composition for oral administration for the treatment of male erectile dysfunction comprising a carrier and active ingredient comprising a dopamine agonist, testosterone or mixtures thereof, the composition being in the form of a fast-dispersing dosage form designed to release the active ingredient rapidly in the oral cavity.
The use of a fast-dispersing dosage form has several advantages over the use of conventional sublingual tablets.
The efficiency of the fast-dispersing dosage form allows low doses to be employed thereby reducing undesirable side effects, particularly nausea and vomiting.
The dosage form acts more quickly than sublingual tablets which allows the dose to be taken when it is required rather than a considerable time before sexual activity. This is both psychologically and socially preferable to sucking a tablet for several minutes in advance of sexual activity.
There is a faster offset of action since the active ingredient is rapidly absorbed rather than absorbed over a prolonged period of time. The faster offset avoids painful persistent erection.
The rapid onset and offset of action is less likely to induce tolerance to the dopamine agonist.
DETAILED DESCRIPTION OF THE INVENTION
One example of a fast-dispersing dosage form is described in U.S. Pat. No. 4,855,326 in which a melt spinnable carrier agent, such as sugar, is combined with an active ingredient and the resulting mixture spun into a “candy-floss” preparation. The spun “candy-floss” product is then compressed into a rapidly dispersing, highly porous solid dosage form.
U.S. Pat. No. 5,120,549 discloses a fast-dispersing matrix system which is prepared by first solidifying a matrix-forming system dispersed in a first solvent and subsequently contacting the solidified matrix with a second solvent that is substantially miscible with the first solvent at a temperature lower than the solidification point of the first solvent, the matrix-forming elements and active ingredient being substantially insoluble in the second solvent, whereby the first solvent is substantially removed resulting in a fast-dispersing matrix.
U.S. Pat. No. 5,079,018 discloses a fast-dispersing dosage form which comprises a porous skeletal structure of a water soluble, hydratable gel or foam forming material that has been hydrated with water, rigidified in the hydrated state with a rigidifying agent and dehydrated with a liquid organic solvent at a temperature of about 0° C. or below to leave spaces in place of hydration liquid.
Published International Application No. WO 93/12769 (PCT/JP93/01631) describes fast-dispersing dosage forms of very low density formed by gelling, with agar, aqueous systems containing the matrix-forming elements and active ingredient, and then removing water by forced air or vacuum drying.
U.S. Pat. No. 5,298,261 discloses fast-dispersing dosage forms which comprise a partially collapsed matrix network that has been vacuum-dried above the collapse temperature of the matrix. However, the matrix is preferably at least partially dried below the equilibrium freezing point of the matrix.
Published International Application No. WO 91/04757 (PCT/US90/05206) discloses fast-dispersing dosage forms which contain an effervescent disintegration agent designed to effervesce on contact with saliva to provide rapid disintegration of the dosage form and dispersion of the active ingredient in the oral cavity.
U.S. Pat. No. 5,595,761 discloses a particulate support matrix for use in making a rapidly dissolving tablet, comprising:
a first polypeptide component
Clarke Anthony
Green Richard David
Johnson Edward Stewart
Momeault Monique A.
Nickey Donald D.
Page Thurman K.
R.P. Scherer Limited
Rozycki Andrew G.
LandOfFree
Image forms and method for ameliorating male erectile... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Image forms and method for ameliorating male erectile..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Image forms and method for ameliorating male erectile... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2865021