WO2005049053A1

WO2005049053A1 - Composition comprising a magnesium compound and/or a magnesium saltfor improving sexual dysfunction

Info

Publication number: WO2005049053A1
Application number: PCT/KR2004/003016
Authority: WO
Inventors: Yong-Geun Kwak; Hyung Sub Kang; Jae-Soon Eun; June-No So; Jong Kwan Park; In-Choul Park
Original assignee: Won Genesis Corporation
Priority date: 2003-11-20
Filing date: 2004-11-19
Publication date: 2005-06-02
Also published as: KR20050048940A

Abstract

The present invention relates to the composition for improving sexual dysfunction comprising one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts. The composition may further comprise L-arginine or ginseng-alcohol extract, or L-arginine and ginseng-alcohol extract. The present invention provides the composition for improving sexual dysfunction having excellent effects, which has no side effects on the human body, is convenient for use and is capable of fundamentally preventing and treating sexual dysfunction.

Description

Composition comprising a magnesium compound and/or a magnesium salt for improving sexual dysfunction

Technical Field

The present invention relates to the composition for improving sexual

dysfunction comprising one or more ingredients selected from the group consisting of

magnesium compounds and magnesium salts.

Background Art

In connection with improved quality of living, the importance placed on sex,

and the recognition and understanding of sex continue to increase. Meanwhile, sexual

dysfunction is a common problem in both males and females. Sexual dysfunction in

males and females is not a problem limited to individuals. Such a problem may induce

familial problems and further, social problems. The penis and clitoris are important

sensory organs for a physiological sexual function, and embryologically homologous

organs. Particularly, the erection in males or females is an essential process during

sexual behavior, and clitoral and penile erections are caused by relaxation of the clitoral

cavernosum and penile corpus cavernosum. In improvement of sexual functions in

males and females, the erections of the clitoris and penis are an important physical

process together with mental state. Penile and clitoral erections are the haemodynamic event which is dependent

upon the balance of contraction and relaxation of the corpus cavernosum smooth

muscles and vasculature of the penis and clitoris (Lemer SE, Melman A, Christ GJ. A

review of erectile dysfunction: new insights and more questions. J Urol. 149:1246-55,

1993).

Relaxation of the penile corpus cavernosum smooth muscle leads to increased

blood flow into the trabecular spaces of the corpus cavernosa, causing them to expand

against the surrounding tunica and compress the draining veins. This produces a vast

elevation in blood pressure which results in an erection (Naylor, AM. Endogenous

neurotransmitters mediating penile erection. Br J Urol. 81:424-31, 1998). Similarly,

relaxation of clitoral cavernosum smooth muscle leads to increased blood flow resulting

in clitoral erection (Goldstein I and Berman JR. Vasculogenic female sexual

dysfunction: vaginal engorgement and clitoral erectile insufficiency syndromes. Int J

Impot Res. 10 Suppl 2:S84-90, 1998). The changes that occur during the penile and clitoral erectile process are

complex and require a high degree of coordinated control involving the peripheral and

central nervous systems, and the endocrine system (Naylor, 1998). Corporal smooth

muscle contraction is modulated by sympathetic noradrenergic innervation via

activation of postsynaptic alphaj adrenoceptors. Erectile Dysfunction may be

associated with an increase in the endogenous smooth muscle tone of the corpus

cavernosum. However, the process of smooth muscle relaxation in the penis and clitoris is mediated partly by non-adrenergic, non-cholinergic (NANC)

neurotransmission. There are a number of other NANC neurotransmitters found in the

penis and clitoris, other than nitric oxide (NO), such as calcitonin gene related peptide

(CGRP) and vasoactive intestinal peptide (VIP). The main relaxing factor responsible

for mediating this relaxation is NO, which is synthesized from L-arginine by nitric

oxide synthase (NOS) (Taub et al 1993; Chuang et al 1998). Reduction of corporal

smooth muscle tone occurs because NO induces relaxation of the corpus cavernosum.

During sexual arousal in males and females, NO is released from neurons and the

endothelium and binds to and activates soluble guanylate cyclase (sGC) located in the

smooth muscle cells and endothelium, leading to an elevation in intracellular cyclic

guanosine 3',5'-monophosphate (cGMP) levels. This elevation in cGMP leads to the

relaxation of the corpus cavernosum due to reduction in the intracellular calcium

concentration ([Ca²⁺],), via unknown mechanisms thought to involve protein kinase G

activation {possibly due to activation of Ca²⁺ pumps and Ca²⁺-activated K⁺ channels

(Chuang et al., 1998)}.

Sildenafil citrate (also known as Viagra™), was recently been developed as the

first oral drug for male erectile dysfunction (MED) by Pfizer. Sildenafil inhibits the

breakdown of cGMP in the penis and clitoris by selectively inhibiting

phosphodiesterase 5 (PDE5), namely inhibiting the hydrolysis of cGMP to 5'GMP

(Boolel et al, 1996; Jeremy et al., 1997), and thereby increasing the mtracellular

concentrations of cGMP and facilitating corpus cavernosal smooth muscle relaxation.. Currently, all other available erectile dysfunction therapies on the market, such

as treatment with prostaglandin based compounds i.e. alprostadil which can be

administered intra-urethrally (available from Vivus Inc., as Muse™) or via small needle

injection (available from Pharmacia & Upjohn, as Caverject™), are inconvenient.

Other treatments include vacuum constriction devices, vasoactive drug injection or

•penile prostheses implantation (Montague DK, Barada JH, Belker AM, Levine LA,

Nadig PW, Roehrborn CG, Sharlip ID, Bennett AH.. Clinical guidelines panel on

erectile dysfunction: summary report on the treatment of organic erectile dysfunction. J

Urol. 156:2007-11, 1996). Although injectable vasoactive drugs show high efficacy,

side effects such as penile pain, fibrosis and priapism are common, thus limiting

applicability for treatment.

In addition, Korean Patent Application Nos. 1999-0019100, 1999-0019101,

1999-0019102, 1999-0019103, 1999-0019104 and 2002-0071326 disclose

pharmaceutical compositions comprising a mixture of two or more ingredients selected

from the group consisting of L-arginine and lycium extract, eucommia bark extract,

acanthopanax extract, schizandra extract, red ginseng extract and evening primrose oil,

but those compositions are likely to tend to exhibit poor effectiveness.

Disclosure of the Invention The present invention relates to a composition for improving sexual

dysfunction comprising one or more ingredients selected from the group consisting of magnesium compounds and magnesium salts.

The composition may further comprise L-arginine or ginseng-alcohol extract,

or L-arginine and ginseng-alcohol extract.

The composition in accordance with the present invention may comprise one

or more ingredients selected from the group consisting of magnesium compounds and

magnesium salts, in an amount of preferably 1 to 80% by weight, and more preferably 5

to 60% by weight of the total weight of the composition, based on the magnesium

content. Further, when the composition in accordance with the present invention

further comprises L-arginine or ginseng-alcohol extract, or L-arginine and ginseng-

alcohol extract, in addition to the magnesium ingredients, preferably, the content of L-

arginine is 1 to 80% by weight based on the total weight of the composition, and the

content of the gmseng-alcohol extract is 1 to 80% by weight based on the total weight

of the composition; more preferably, the content of L-arginine is 5 to 50% by weight

based on the total weight of the composition, and the content of the ginseng-alcohol

extract is 2 to 50% by weight based on the total weight of the composition.

The composition in accordance with the present invention may be

administered 1 to 3 times per day, 0.001 to 3 g each time, and preferably 1 to 3 times

per day, 0.01 to 2 g each time, based on the magnesium contents from magnesium

compounds or magnesium salts contained in the composition. Magnesium, one of electrolytes essential for all the cells of body, maintains

functions of muscles and neurons, maintains a constant cardiac rate, is important for bone growth and also is absolutely necessary for energy metabolism and protein synthesis (Wester PO. Magnesium. Am J Clin Nutr 1987;45:1305-12). Thus magnesium deficiency is known to cause a variety of diseases (Johnson S. The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses. 2001 56:163-70).

The present inventors have found that magnesium facilitates production and liberation of nitric oxide (NO) in penile corpus cavernosum and clitoral cavernosum, and applied this finding to the present invention. Therefore, the composition in accordance with the present invention has an effect on improving sexual dysfunction by promoting production and liberation of nitric oxide (NO) in penile corpus cavernosum and clitoral cavernosum, resulting in relaxation of smooth muscles thus leading to increased blood flow to the penis and clitoris.

The representative examples of magnesium compounds in according to the

, present invention are magnesium oxide, magnesium hydroxide and the like. In addition, the representative examples of magnesium salts in according to the present invention are magnesium chloride, magnesium sulfate, magnesium gluconate, magnesium citrate, magnesium lactate, magnesium stearate and the like. In particular, magnesium gluconate, magnesium citrate, magnesium lactate and magnesium oxide are more preferable. The compositions in accordance with the present invention comprising not only magnesium compounds and/or magnesium salts, but also a ginseng-alcohol extract containing L-arginine (used as a substrate of NO) and gmsenosides which are

known as a stimulator and an expression inducer of NOS (Li Z, Niwa Y, Sakamoto S,

Shono M, Chen X, Nakaya Y. Induction of inducible nitric oxide synthase by

gmsenosides in cultured porcine endothelial cells. Life Sci. 2000;67:2983-9; Scott GI,

Colligan PB, Ren BH, Ren J. Ginsenosides Rbl and Re decrease cardiac contraction in

adult rat ventricular myocytes: role of nitric oxide. Br J Pharmacol 2001,134:1159-65),

show an excellent effects on improving sexual dysfunction. In this connection, it is

important that it is the composition of which the amount of each constituent is regulated

to have a synergistic effects without side effects. If each constituent is used in an excessive amount, it may cause side effects

such as decreased preference and loss of impotence-treating effect. In order to

significantly improve such problems, the composition in accordance with the present

invention was prepared such that it was a composite composition of which the amount

of each material necessary for NO synthesis and liberation was reduced, very

efficiently increasing the relaxation of corpus cavernosum by NO. Thus the effect as a

sexual dysfunction-improving agent was enhanced.

One characteristic of the composition in accordance with the present

invention is that it may improve peripheral blood circulation leading to fundamental

improvement of sexual dysfunction and have the preventing and treating effects for

such diseases, since the composition contains a magnesium salt which is known to

prevent cardiovascular diseases including diabetes mellitus and hypertension, and senescence which are fundamental causes of sexual dysfunction.

The ginseng-alcohol extract in the composition in accordance with the

present invention is obtained by placing dried ginseng in 1 to 10-fold weight of

ethanol or a mixed solvent of ethanol and water, followed by extraction at a

temperature of 20 to 78°C for 1 to 10 hours, and then concentrating and freeze-drying

the resulting filtrate.

The composition for improving sexual dysfunction in accordance with the

present invention may be formulated in various forms that contain pharmaceutically

acceptable carriers, excipients and/or additives. That is, the composition in

accordance with the present invention may be formulated in the form of a

conventional formulation, for example oral formulations such as tablets, capsules and

solutions, and parenteral formulations such as injectable preparations and transdermal

preparations. Examples of transdermal preparations may include creams, gels,

ointments and lotions. The composition in accordance with the present invention may be used in

various food products. For example, the composition of the present invention may

be prepared in the form of food products such as teas and health supplements.

Brief Explanation of Drawings

The above and other objects, features and other advantages of the present

invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

Fig. 1 is a graph showing concentration-dependent effects of L-arginine,

ginseng-alcohol extract and magnesium gluconate on penile corpus cavernosum

relaxation. ; Fig. 2 is a graph showing concentration-dependent effects of L-arginine,

ginseng-alcohol extract and magnesium gluconate on clitoral cavernosum relaxation.;

Fig. 3 is a bar graph showing the comparison of the relaxation effects on penile

corpus cavernosum among the group in which L-arginine alone was administered, the

group in which a combination of L-arginine and ginseng-alcohol extract was

administered, and the group in which a combination of L-arginine, ginseng-alcohol

extract and magnesium gluconate was administered; and

Fig. 4 is a bar graph showing the inhibition effects of L-NAME (10^" M, an

inhibitor of nitric oxide synthase) on penile corpus cavernosum relaxation induced by

the combination of L-arginine, ginseng-alcohol extract and magnesium gluconate.

Best Mode for Carrying Out the Invention

Now, the present invention will be described in more detail with reference to

the following Examples and Experimental Examples. These examples are provided

only for illustrating the present invention and should not be construed as limiting the

scope and sprit of the present invention. EXAMPLES

Example 1 : Preparation of ginseng-alcohol extract

One kg of dried 4-year white ginseng was placed in 3L of 70% ethanol,

followed by heat extraction for 5 hours and filtration. The filtrate obtained was further

concentrated and the resulting concentrate was freeze-dried.

Formulation Example 1 : Tablet

Magnesium gluconate 400.0 g Lactose BP 250.0 mg

Starch BP 30.0 mg

Pre-gelatinized corn starch BP 15.0 mg

Magnesium stearate 1.0 mg

Magnesium gluconate was mixed with lactose, starch and pre-gelatinized corn

starch, adequate volume of purified water was added thereto and granulated. The

granules were dried, mixed with magnesium stearate, and then compressed to prepare a

tablet.

Formulation Example 2 : Tablet

Magnesium oxide 200.0 mg L-arginine 200.0 mg

Ginseng-alcohol extract 100.0 mg

Lactose BP 250.0 mg

Starch BP 30.0 mg Pre-gelatinized corn starch BP 15.0 mg

Magnesium stearate 1.0 mg

Magnesium oxide, L-arginine and ginseng-alcohol extract were mixed with

lactose, starch and pre-gelatinized com starch. Adequate volume of purified water was

added thereto and granulated. The granules were dried, mixed with magnesium

stearate, and then compressed to prepare a tablet.

Formulation Example 3 : Capsule

Magnesium gluconate 200.0 mg Starch 1500 100.0 mg

Magnesium stearate BP 1.0 mg

Magnesium gluconate was mixed with starch and magnesium stearate, and the

mixture was filled into a gelatin capsule to prepare a capsule.

Formulation Example 4 : Capsule Magnesium oxide 150.0 mg

L-arginine 150.0 mg

Ginseng-alcohol extract 100.0 mg

Starch 1500 100.0 mg

Magnesium stearate BP 1.0 mg

Magnesium oxide, L-arginine and ginseng-alcohol extract were mixed with

starch and magnesium stearate. The mixture was filled into a gelatin capsule to prepare

a capsule.

Formulation Example 5 : Injectable preparation

Magnesium gluconate 30.0 mg

L-arginine 30.0 mg

Ginseng-alcohol extract 13.0 mg

Dilute sodium hydroxide pH 7.5-8.5

Sodium chloride BP for injection Max. 2 ml

Magnesium gluconate, L-arginine and ginseng-alcohol extract were dissolved

in an appropriate volume of a dilute sodium hydroxide solution to adjust to pH 7.5 to

8.5. Then sodium chloride BP for injection was used to adjust a volume of the solution

and was thoroughly mixed. The resulting solution was filled into a 2 ml ampoule made of transparent glass. The glass was melted to seal the ampoule under the upper

grid of air and then sterilized in an autoclave to prepare an injectable preparation.

Formulation Example 6 : Cream formulation Composition (wt%)

Magnesium gluconate 30.0

L-arginine 30.0

Ginseng-alcohol extract 13.0

Dimethicone 5 Cyclomethicone 5

Cetylethyl hexanoate 5

Cetanol 2

Stearic acid 2

Glycerol monostearate 2 Polyoxyethylene sorbitan .

Monostearate 5

Ethanol 5

Propylene glycol 5

Citric acid 0.3 Keltrol F 0.2

Methyl paraben 0.2 Floral Musk incense 0.1

Purified water balance

Preparation method

(1) Dimethicone, cyclomethicone, cetylethyl hexanoate, cetanol, stearic acid, glycerol monostearate, polyoxyethylene sorbitan monostearate and methyl paraben were dissolved by increasing the temperature to 75°C.

(2) Magnesium gluconate, L-arginine, ginseng-alcohol extract, propylene glycol, citric acid, Keltrol F and purified water were dissolved by increasing the temperature to 75°C.

(3) The solution of step (1) was poured into the solution of step (2) and

emulsified while mixing under stirring.

(4) Ethanol and Floral Musk incense were added during emulsification.

(5) The mixture was cooled below 30°C to prepare a cream.

Formulation Example 7 : Gel formulation

Composition (wt%

Magnesium gluconate 30.0

L-arginine 30.0

Ginseng-alcohol extract 13.0

Carbopol Cetylethyl hexanoate 0 Isostearic acid 2 Polyoxyethylene sorbitan Monostearate 5 Ethanol 5 Citric acid 0.3 Sepigel 305 0.5 Propyl paraben 0.2 Floral Musk incense 0.1 Purified water balance

Preparation method

(1) Carbopol was dissolved in purified water.

(2) Magnesium gluconate, L-arginine, ginseng-alcohol extract, cetylethyl hexanoate, isostearic acid, polyoxyethylene sorbitan monostearate, ethanol, citric acid, propylparaben and Floral Musk incense were dissolved in the solution of step (1).

(3) To the solution of step (2) was added Sepigel 305, and then mixed and stirred.

(4) Gel was prepared.

Experimental Example 1: Test of corpus cavernosum relaxation effects

In the present invention, tissues for experiments were prepared from New Zealand White rabbits, weighing 2.5 to 3.0 kg. Each rabbit was anesthetized by

injection of sodium thiopental (30 mg/kg) into the ear vein and the entire penis or

clitoris was excised from the pelvic bone and then only corpus cavernosum tissue was

separated. During the preparation, care was taken not to apply excessive

manipulation, in order to prevent damage of the endothelium present in tissues. Tissue

strips (1 2 x 7 mm) were obtained from the separated corpus cavernosum smooth

muscle. Each end of the rabbit corpus cavernosum strip was secured using a silk

suture (6-zero) and then one end was connected with a transducer (Grass Research

Polygraph, Model 79H, W. Warwick, RI) for tension measurement and the other end

was connected with one end of an organ bath. During securing the tissues, care was

taken to avoid overstretching, in order to prevent damage to the endothelial tissues.

A strip of male rabbit penile corpus cavernosum tissue and a strip of female

rabbit clitoral cavernosum tissue were vertically placed in 5ml of the organ bath and the

tension produced in the tissues was recorded on physiograph paper. A nutrient

solution used had the following composition in mM: NaCl 118, KCl 4.7, CaCl₂ 2.5,

MgCl₂ 2, NaHC0₃ 25, glucose 10 and HEPES 10, and pH thereof was adjusted to 7.4

using IN NaOH. Further, the nutrient solution was saturated with 100% oxygen, and

the temperature of the organ bath was maintained at 37°C.

The above-mentioned tissue was initially adjusted at 1 g of basal tension and

allowed to stabilize for 60 min, prior to initiation of the present experiment. Changes

in tension occurred during the experiment was recorded on physiograph paper. Drug administration was performed in a cumulative manner, from lower concentration to

higher concentration, and when maximum relaxation was reached, the second order-

concentration of drug was administered. Upon administering a fresh drag, the tissue

was washed with a fresh nutrient solution three times and allowed to stabilize for about

20 min.

Expression of tension was based on a maximum contraction point or a

minimum relaxation point occurred when the drug was administered. After

confirming that there was no damage to the endothelial cells by observing a contraction

response due to phenylephrine (PhE) and a relaxation response due to acetylcholine

(ACh), the organ bath was washed with a fresh nutrient solution. After PhE was

administered again to cause contraction, each of L-arginine (0.1, 0.3, 0.6 and 1 g/L),

ginseng-alcohol extract (0.01, 0.03, 0.1, 0.3 and 1 g/L), and magnesium gluconate

(0.01, 0.03, 0.1, 0.3 and 1 g/L) was administered in a cumulative dose, followed by

observation of a relaxation response. In addition, relaxation effects between the group

in which a combination of L-arginine (1 g/L) and ginseng-alcohol extract (1 g/L) was

administered, and the group in which a combination of L-arginine (1 g/L), ginseng-

alcohol extract (1 g/ L) and magnesium gluconate (1 g/L) was administered were

observed and compared. Further, based on the comparison of relaxation effects on

the corpus cavernosum between the group in which a combination of L-arginine (0.1

g/L), ginseng-alcohol extract (0.1 g/L) and magnesium gluconate (0.1 g/L) was

administered after corpus cavernosum tissue was pre- treated for 30 min with L-NAME (10^" M, an inhibitor of nitric oxide synthase) and contracted with PhE, and the group

in which a combination of the same ingredients and contents administered without

pre-treatment of L-NAME (10^"3 M), a relationship between the relaxation effect of the

composite composition and the NO system was elucidated. As a result of test of responses to PhE and ACh, sections of all the cases

(penile corpus cavernosum, n = 22; clitoral cavernosum, n = 25) exhibited a contraction

response to PhE(10^"5 M). Among tissues contracted with PhE, the number of tissue

that exhibited a relaxation response to 10^"5 M ACh was 22 cases in the penis and 25

cases in the clitoris. In addition, it was confirmed that there was no damage to the

endothelium surrounding the inner space of the corpus cavernosum from the relaxation

response due to ACh.

As shown in Fig. 1, each of L-arginine (0.1, 0.3, 0.6 and 1 g/L), ginseng-

alcohol extract (0.01, 0.03, 0.1, 0.3 and 1 g/L), and magnesium gluconate (0.01, 0.03,

0.1, 0.3 and 1 g/L) exhibited relaxation responses of penile corpus cavernosum in a

dose-dependent manner. In particular, 1 g/L of L-arginine or magnesium gluconate

exhibited the strong relaxation effect that was similar to relaxation effect of penile

corpus cavernosum in response to 10 μM (micromole) ACh. Additionally, also in the

clitoris, each of L-arginine (0.1, 0.3, 0.6 and 1 g/L), ginseng-alcohol extract (0.01, 0.03,

0.1, 0.3 and 1 g/L), and magnesium gluconate (0.01, 0.03, 0.1, 0.3 and 1 g/L) exhibited

the relaxation responses of the clitoral cavernosum in a dose-dependent manner (see

Fig. 2). Interestingly, as shown in Fig. 3, it was observed that the group treated with the combination of L-arginine (1 g/L) and ginseng-alcohol extract (1 g/L) had a

significantly enhanced relaxation effect in the presence of magnesium gluconate (1

g/L). In addition, when pre-treated with L-NAME (10^"3 M) for 30 min, relaxation

effects of a composite composition made up of L-arginine (0.1 g/L), gmseng-alcohol

extract (0.1 g/ L) and magnesium gluconate (0.1 g/L) were significantly inhibited, as

compared to the case (control group) in which a combination of the same ingredients

and contents was administered without pre-treatment of L-NAME (10^"3 M) (see Fig.

4). These experimental results strongly suggest that relaxation effects of the

composite composition are brought about through action on the NO system.

Industrial Applicability

As described above, the present invention provides a composition for improving

sexual dysfunction having excellent effects which has no side effects on the human

body, is convenient for use and is capable of fundamentally preventing and treating

sexual dysfunction.

Claims

1. A composition for improving sexual dysfunction comprising one or more

ingredients selected from the group consisting of magnesium compounds and

magnesium salts.

2. The composition for improving sexual dysfunction as set forth in claim 1,

further comprising L-arginine or ginseng-alcohol extract, or L-arginine and ginseng-

alcohol extract.

3. The composition for improving sexual dysfunction as set forth in claim 1,

wherein the magnesium compound is selected from the group consisting of magnesium

oxide and magnesium hydroxide, and the magnesium salt is selected from the .group

consisting of magnesium chloride, magnesium sulfate, magnesium gluconate,

magnesium citrate, magnesium lactate, and magnesium stearate.

4. The composition for improving sexual dysfunction as set forth in claim 1,

wherein one or more ingredients selected from the group consisting of magnesium

compounds and magnesium salts is included in an amount of 1 to 80% by weight of the

total weight of the composition, based on the magnesium content.

5. The composition for improving sexual dysfunction as set forth in claim 2,

wherein the content of L-arginine is 1 to 80% by weight based on the total weight of

the composition, and the content of the ginseng-alcohol extract is 1 to 80% by weight

based on the total weight of the composition.

6. The composition for improving sexual dysfunction as set forth in claim 1 or 2,

wherein the magnesium compound or magnesium salt included in the composition is

administered 1 to 3 times per day, 0.001 to 3 g each time, based on the magnesium

content.

7. The composition for improving sexual dysfunction as set forth in claim 2,

wherein the ginseng-alcohol extract is obtained by placing dried ginseng in 1 to 10-

fold weight of ethanol or a mixed solvent of ethanol and water, followed by extraction

at a temperature of 20 to 78°C for 1 to 10 hours, and then concentrating and freeze-

drying the resulting filtrate.

8. A food product comprising the composition of Claim 1 or 2.

9. A method for improving sexual dysfunction, comprising: administering a therapeutically effective amount of a composition of Claim 1

or 2 to humans.

0. Use of a composition of Claim 1 or 2 for improving sexual dysfunction.