| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | December 14, 1993 |
| PATENT TITLE |
Method of treating impotence |
| PATENT ABSTRACT |
A method of relieving erectile impotence in a human male. The method comprises administering to the male an erectile impotence relieving amount of a compound selected from the group consisting of U.K. 52,046, Amlodipine, Doxazosin and the pharmaceutically acceptable acid addition salts thereof. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | March 11, 1993 |
| PATENT REFERENCES CITED |
Morales, et al., "Is Yohimbine Effective in the Treatment of Organic Impotence? Results of a Controlled Trial", The Journal of Urology 137: 1168-1172 (1987). Bommer, et al., "Improved Sexual Function in Male Haemodialysis Patients on Bromocriptine", The Lancet, Sep. 8, 1979, pp. 496-497. Antoniou, et al., "Reversal of Uraemic Impotence by Zinc", The Lancet, Oct. 29, 1977, pp. 895-898. Mudd, John W., "Impotence Responsive to Glyceryl Trinitrate", Am. J. Psychiatry 134:8, Aug. 1977. Brindley, G. S., "Pilot Experiments on the Actions of Drugs Injected Into the Human Corpus Cavernosum Penis", Br. J. Pharmac. 87: 495-500 (1986). Rayner, et al., "Penile Erection Due to Nifedipine", Brit. Med. J. 296: 137 (1988). R. R. Luther, Am. J. Hypertension, vol. 2, No. 9, pp. 729-735, Sep. 1989, The American Journal of Hypertension, Inc., "New perspectives on selective alpha 1 blockade". F. Holmquist et. al., European Journal of Pharmacology, vol. 186, pp. 87-93, Sep. 1990, Elsevier Science Publishers B. V. (Biomedical Division) "Effect of the alpha 1-adrenoceptor antagonist R-(-)-YM126217 on isolated human penile erectile tissue and vas deferens". H. Hedlund et. al., J. Autonon. Pharmacol., vol. 5, pp. 81-88, 1985, "Comparison of the responses to drugs acting on adrenoreceptors and muscarinic receptors in human isolated corpus cavernosum and cavernous artery". |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
We claim: 1. A method of relieving erectile impotence in a human male comprising administering to said male an erectile impotence relieving amount of the compound U.K.-52,046 and the pharmaceutically acceptable acid addition salts thereof. 2. The method as recited in claim 1 wherein the compound is the mesylate salt. 3. The method as recited in claim 1 wherein the compound is administered by injection. 4. The method as recited in claim 1 wherein the compound is administered transdermally. 5. The method as recited in claim 2 wherein a single dosage is about 0.1 .mu.g to about 25 .mu.g. 6. The method as recited in claim 3 wherein a single dosage is about 10 .mu.g to about 100 mg. 7. The method as recited in claim 1 wherein the compound is the methane sulfonate salt of U.K. 52,046 |
| PATENT DESCRIPTION |
TECHNICAL FIELD The field of art to which this invention pertains is methods of treating male erectile impotence and more particularly the use of erection enhancing compounds to treat male erectile impotence. BACKGROUND ART Impotence is the inability to obtain and sustain an erection sufficient for intercourse. The penis becomes erect when certain tissues (in particular, the corpora cavernosa) in the central portion of the penis becomes engorged with blood thereby causing them to become less flaccid, and in turn causing an erection. It is estimated that 10-12 million American men between the ages of 18 and 75 suffer from chronic impotence with the great majority being over the age of 55. Impotence results from psychologic disturbances (psychogenic), from physiologic abnormalities (organic) or from a combination of both. Typically, multiple factors are responsible for impotence. The major causes of organic impotence are vascular abnormalities, neurologic deficiencies and drug treatment side effects. The primary vascular causes of impotence are arterial insufficiency, which prevents the penis from filling with blood, and venous abnormalities that prevent the retention of blood in the penis during the erectile process. Arterial insufficiency is primarily due to atherosclerosis and has been found to be exacerbated by smoking. A less frequent and somewhat unlikely vascular cause of impotence is priapism, prolonged painful erection, which can cause hypoxia and death of penile tissue. The search for impotence treatment methods has included external devices for example, tourniquets (see U.S. Pat. No. 2,818,855). In addition penile implants, such as hinged or solids rods and inflatable, spring driven or hydraulic models, have been used for some time. The administration of erection effecting and enhancing drugs is taught in U.S. Pat. No. 4,127,118. That patent teaches a method of treating male impotence by injecting into the penis an appropriate vasodilator, in particular, an adrenergic blocking agent or a smooth muscle relaxant to effect and enhance an erection. More recently U.S. Pat. No. 4,801,587 teaches the application of an ointment to relieve impotence. The ointment consists of the vasodilators papaverine, hydralazine, sodium nitroprusside, phenoxybenzamine, or phentolamine and a carrier to assist absorption of the primary agent through the skin. In addition, Yohimbine, an alpha adrenergic antagonist is currently marketed with the suggestion that it may be efficacious in treating psychogenic impotence. Although the injection of such agents as papaverine into the corpora cavernosa has proven effective, typically large doses 8 to 32 mg are required, resulting in undesired side effects such as pain, priapism and tissue fibrosis. The other impotence relieving agents also have one or more of the above problems when administered intracavernosally. Thus, there is a continuing search in this field of art for improved methods for relieving male erectile impotence. SUMMARY OF THE INVENTION The invention is directed to a method of relieving erectile impotence in a human male. The method comprises administering to the male an erectile impotence relieving amount of a compound selected from the group consisting of U.K. 52,046, Amlodipine, Doxazosin and the pharmaceutically acceptable acid addition salts thereof. Other features and advantages will be apparent from the specification and claims. DETAILED DESCRIPTION OF THE INVENTION Doxazosin, which has the chemical structure: ##STR1## and its pharmaceutically acceptable acid addition salts are described in commonly assigned U.S. Pat. No. 4,188,390, entitled "Antihypertensive 4-Amino-2-[4(1,4-Benzodioxan-2-carbonyl)Piperazin-1-yl or Homopiperazin-1-yl]Quinazolines", the disclosure of which is hereby incorporated by reference. U.K.-52,046, which has the chemical structure ##STR2## and its pharmaceutically acceptable acid addition salts are described in commonly assigned U.S. Pat. No. 4,686,228, entitled "Quinoline Therapeutic Agents", the disclosure of which is hereby incorporated by reference. Amlodipine, which has the chemical structure ##STR3## and its pharmaceutically acceptable acid addition salts are described in commonly assigned U.S. Pat. No. 4,572,909, entitled "2-(Secondary Aminoalkoxymethyl)Dihydropyridine Derivatives as Anti-Ischaemic And Antihypertensive Agents", the disclosure of which is hereby incorporated by reference. Although the generic names Doxazosin, Amlodipine and U.K. 52,046 represent the free base, the present invention is also meant to embrace their pharmaceutically acceptable acid addition salts, such as hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, salicylate, succinate, maleate, gluconate, methane sulfate, ethane sulfate, methane sulfonate (mesylate), benzenesulfonate (besylate), toluene sulfonate and p-toluenesulfonate salts. However preferred are the mesylate or besylate salts. Any method of administration of the above compounds found effective in relieving male erectile impotence may be used. Preferably the administration is parenteral (e.g. injection, air gun) or transdermal (e.g. iontophoresis, passive transport) as these methods direct the compound to the critical tissues. For purposes of parenteral administration, (e.g. intracavernosal) solutions of these particular compounds in sesame or peanut oil or in aqueous propylene glycol may be employed, as well as sterile aqueous solutions of the corresponding water soluble acid addition salts previously enumerated. Such aqueous solutions should be suitably buffered if necessary. These particular aqueous solutions are especially suitable for intracavernosal injection purposes. In this connection, the sterile aqueous media employed are readily obtained by standard techniques well known to those skilled in the art. For instance, distilled water is ordinarily used as the liquid diluent and the final preparation is passed through a suitable bacterial filter such as a sintered glass filter or a diatomaceous-earth or unglazed porcelain filter. Preferred filters of this type include the Berkefeld, the Chamberland and the Asbestos Disk-Metal Seitz filter, wherein the fluid is sucked into a sterile container with the aid of a suction pump. Needless to say, the necessary steps should be taken throughout the preparation of these injectable solutions to insure that the final products are obtained in a sterile condition. The injection can be made by needle or air gun. Typically the injection is made into the corpus cavernosum although any injection that is effective in relieving impotences may be used. Any amount of the above described compounds when administered by injection that is effective in relieving male erectile impotence may be used. Because the compounds are vasodilators the drugs can reduce the blood pressure resulting in systemic cardiovascular effects (e.g. fainting). Thus, preferably the amount is below that amount which is the threshold limit for a significant systemic cardiovascular effect. The frequency of delivery, of the amounts described below, relates to the frequency of impotence relief. Typically the compounds are administered just prior to the desire to obtain and sustain an erection. However as previously stated the total amount delivered is preferably below the threshold limit for significant systemic cardiovascular effects. Preferably about 0.1 .mu.g to about 25 .mu.g U.K.-52,046 is used in a single dose. Preferably about 0.125 mg to about 5 mg Doxazosin is used in a single dose. Preferably about 0.125 mg to about 10 mg Amlodipine is used in a single dose. Below the lower limit the compounds are not effective and above the upper limit significant systemic cardiovascular effects may occur. The above described compounds can also be administered transdermally. For purposes of transdermal administration, the dosage from of the particular compound may include, by way of example, solutions, lotions, ointments, creams, gels, suppositories, rate-limiting sustained release formulations and devices therefor. Such dosage forms comprise the particular compound and may include ethanol, water, penetration enhancer and inert carriers such as gel-producing materials, mineral oil, emulsifying agents, benzyl alcohol and the like. Specific transdermal flux enhancing compositions are disclosed in commonly assigned co-pending U.S. patent application Ser. No. 925,641, the teachings of which are incorporated by reference. That specification teaches a transdermal flux composition comprising a pharmacologically active compound or a prodrug thereof, an aqueous ethanol solvent containing from 15% to 75% ethanol by volume and cis-olefin compounds such as oleic acid. For transdermal administration the compounds may, for example, simply be applied directly to the penis. In another method of transdermal application the compounds may be delivered transdermally utilizing iontophoresis. In iontophoresis a drug is transported from a solution (disposed against the skin) across the dermal barrier by the application of a current across the solution and skin. Any amount of the above described compounds when administered transdermally that is effective in relieving male erectile impotence may be used. Typically the same amounts are preferably delivered to the critical tissues as are delivered by injection, however the amounts applied transdermally are typically greater because of the low effectiveness of transdermal administration for delivery to the critical tissues. As with injection, the amounts delivered are preferably below the threshold limit for significant systemic cardiovascular effects. The frequency of delivery is the same as described for injection. The amounts detailed below are for passive transdermal delivery. It is believed that for iontophoretic delivery the ranges would be reduced by a factor of 10 based on the greater efficiency of iontophoretic delivery. Thus, preferably about 100 .mu.g to about 100 mg U.K.-52,046 is used in a single dose. Preferably about 0.5 mg to about 500 mg Doxazosin is used in a single dose. Preferably about 20 mg to about 20 g Amlodipine is used in a single dose. |
| PATENT EXAMPLES | Available on request |
| PATENT PHOTOCOPY | Available on request |
|
Want more information ? Interested in the hidden information ? Click here and do your request. |