1. Field of the invention
The present invention relates to the treatment of sexual dysfunction and, more particularly, to an improved natural composition and method for treatment of erectile dysfunction and female sexual dysfunction using a combination of L-arginine, ginseng and Zizyphi fructus in an orally administered dosage.
2. Description of the Background
The most prevalent type of sexual dysfunction is "Erectile Dysfunction", e.g., "the inability to achieve and/or maintain an erection sufficient for sexual activity" (New England Journal of Medicine). Erectile dysfunction is most often attributable to the inability to generate enough NO in the corpus cavernosum.
The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
There is one well-established solution. Viagra.RTM. is an oral drug for erectile dysfunction made by Pfizer, Inc. Viagra.RTM. received FDA approval on Mar. 27 1998, and has since Viagra.RTM. has given new hope to over 30 million men that suffer from the problem. Viagra.RTM. was proven effective in 7 out of 10 men in clinical trials.
Viagra.RTM. is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosinemonophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate and has the structural formula shown in FIG. 1.
Sildenafil citrate is a crystalline powder, and Viagra.RTM. puts this in tablet form equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake.
Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum.
Although there are few known side-effects with Viagra.RTM., it is a drug that required full FDA approval, and physicians must prescribe its usage and dosage for their patients. Unfortunately, a significant stigma is attached to erectile dysfunction, and many of its sufferers simply will not seek medical help. Thus, Viagra.RTM. remains unavailable to a large proportion of the affected population. It would be greatly advantageous to provide a natural and organic alternative treatment with the same or similar benefits, but without the same level of risk.
It is known that the same or similar benefits can be achieved by a different mechanism than Viagra.RTM.. Again, Viagra.RTM. inhibits phosphodiesterase type 5 (PDE5), which slows the degradation of cGMP in the corpus cavernosum. The resulting increased levels of cGMP in the corpus cavernosum results in smooth muscle relaxation. In contrast, it is possible to foster smooth muscle relaxation directly by stimulating the release of NO in the corpus cavernosum during sexual stimulation. The NO in turn is acted upon by the enzyme guanylate cyclase, which results in increased levels of cGMP, again producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. See, e.g., Rajfer et al., Nitric Oxide as a Mediator of Relaxation of the Corpus Cavernosum in Response to Nonadrenergic, Noncholinergic Neurotransmission, N. Engl. J. Med., 326(2), pp. 90-4 (Jan 9, 1992).
Notwithstanding there are relatively few studies that suggest how to stimulate the release of NO in the corpus cavernosum.
It is recognized that NO-nitro-L-arginine is an inhibitor of nitric oxide synthase, and studies have shown that concentrations of NO-nitro-L-arginine (3.times.10(-S) mol/l) can abolish relaxations. Moreover, the inhibitory effect of NO-nitro-L-arginine can be reversed in the presence of L-arginine (3.times.10(-3) mol/l). Simonsen et al., Nitric Oxide Is Involved in the Inhibitory Neurotransmission and Endothelium-dependent Relaxations of Human Small Penile Arteries, Clin. Sci. (Colch) 92:3, pp. 269-75 (March 1997). This research suggests that L-arginine can be an effective substrate for NO synthase, and may stimulate the release of NO in the corpus cavemosum.
Beside the use of L-arginine, there is little to suggest how to stimulate the release of NO in the corpus cavernosum. It would be greatly advantageous to combine the use of L-arginine with other natural and organic constituents to stimulate enough release of NO in the corpus cavernosum to produce and sustain smooth muscle relaxation in the corpus cavernosum, allowing inflow of blood, and alleviating erectile dysfunction.
It would also be advantageous to provide a composition as described above which is also effective for treating sexual conditions in females. It has been found that clitoral smooth muscle cells include many of the same morphological characteristics as the male corpus cavernosum, and should be physiologically responsive via the same messengers (cGMP) to promote smooth muscle relaxation. Park et al., Morphological/Biochemical Characterization of Human Corpus Clitoral Smooth Muscle Cells in Culture, Journal. of Urology, v. 159, n. 5, sup. (June 1998). Thus, that which promotes smooth muscle relaxation in the corpus cavernosum, allowing inflow of blood, and alleviating erectile dysfunction, should work well to alleviate female sexual dysfunction. Indeed, women claim to experience benefit from Viagra.RTM. and clinical tests are now being performed.