KR20050048940A - Composition comprising a magnesium compound and/or a magnesium salt for improving sexual dysfunction - Google Patents

Abstract

The present invention relates to a composition for improving sexual dysfunction comprising at least one component 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 a composition for improving sexual dysfunction, which has no side effects on the human body, is simple to use, and has an excellent effect of fundamentally preventing and treating sexual dysfunction.

Description

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

The present invention relates to a composition for improving sexual dysfunction comprising at least one component selected from the group consisting of magnesium compounds and magnesium salts.

In improving the quality of life, the share of sex is increasing and the concept of sex has become open. Therefore, sexual dysfunction is a common problem for both men and women. Men's and women's sexual dysfunction is not limited to individuals, but is always relative, and can spread to family-wide problems and even society-wide issues. Penis and clitoris are important sensory organs and physiologically homologous in physiological sexual function. In particular, for men and women, erection is an essential process during sexual activity, and erection of the clitoris and penis is caused by relaxation of the clitoris cavernous body and the corpus cavernosum. In improving the sexual function of men and women, clitoris and erection of the penis, along with mental sympathy, are important physical processes.

The penis and clitoris erection is a hemodynamic event that depends on the balance of contraction and relaxation of cavernous smooth muscle and pulmonary system (Lerner SE, Melman A, Christ GJ.A review of erectile dysfunction: new insights and more questions.J Urol. 149: 1246 -55, 1993).

Relaxation of the corpus cavernosum smooth muscle induces increased blood flow to the trabecular spaces of the corpus cavernosum, causing it to expand over the surrounding membrane and compress the draining vein. This leads to a very elevated blood pressure resulting in erection (Naylor, AM. Endogenous neurotransmitters mediating penile erection. Br J Urol. 81: 424-31, 1998). In the case of the clitoris, the blood volume increases due to the relaxation of the clitoris cavernous smooth muscle, leading to clitoris 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).

Changes that occur during the penis and clitoris erection process are complex and require highly integrated regulation involving the peripheral and central nervous and endocrine systems (Naylor, 1998). Cavernous smooth muscle contraction is regulated by sympathetic noradrenergic neurostimulation through activation of postsynaptic α ₁ adrenergic receptors. Erectile dysfunction may be associated with an increase in the endogenous smooth muscle tension of the cavernous body. However, the process of smooth muscle relaxation of the penis and clitoris is partially mediated by non-drenergic, noncholinergic (NANC) neurotransmission. Several other NANC neurotransmitters besides NO, such as calcitonin gene related peptides (CGRP) and vasoactive intestinal peptides (VIP), are found in the penis and clitoris. The major relaxation factor responsible for mediating this relaxation is nitric oxide (NO), which is synthesized from L-arginine by nitric oxide synthase (NOS) (Taub et al 1993; Chuang et al 1998). The decrease in cavernous smooth muscle tension is due to NO inducing relaxation of the cavernous body. During sexual arousal, NO binds to and activates soluble guanylate cyclase (sGC) released from neurons and endothelium and located in smooth muscle cells and endothelium, thereby intracellular cyclic guanosine 3 ', 5'-monophosphate ( cGMP) level. This increase in cGMP levels is attributed to intracellular calcium concentration ([Ca] via an unknown mechanism that is thought to be involved in protein kinase G activation (probably due to activation of Ca ²⁺ pumps and Ca ^{2+ -activated} K ⁺ channels). ²⁺ ] _i ) leads to relaxation of the cavernous body due to a decrease in (Chuang et al., 1998).

Sildenafil citrate (also known as Viagra ^™ ) was recently developed by Pfizer as the first oral drug treatment for MED. Sildenafil selectively inhibits phosphodiesterase 5 (PDE5) in the penis and clitoris to inhibit cGMP degradation, thereby limiting the hydrolysis of cGMP to 5'GMP (Boolel et al ., 1996; Jeremy et al. , 1997) thereby increasing the intracellular concentration of cGMP and facilitating the relaxation of cavernous smooth muscle.

At present, all other erectile dysfunction therapies, such as treatment with prostaglandin preparations, ie can be administered into the urethra (available as Muse ^TM from Vivus Inc.) with small needles Alprostadil, which is injected (commercially available as Caverject ^™ from Pharmacia & Upjohn), is inconvenient. Other treatments include vacuum contractors, vascular injections or penile implants (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.The American Urological Association.J Urol. 156: 2007-11, 1996).

It includes. Injectable vasoactive drugs are highly efficacious, but side effects such as penile pain, fibrosis and sustained erection frequently occur and are constrained for use in therapy.

In addition, Korean Patent Application Nos. 99-19100, 99-19101, 99-19102, 99-19103, 99-19104, and 2002-0071326, L-arginine and goji berry extract, tofu extract, It discloses a pharmaceutical composition consisting of two or more mixtures selected from the group consisting of prickly pear extract, Schisandra chinensis extract, red ginseng extract, and walnut oil, but the effect tends to be inferior.

It is an object of the present invention to provide a composition for improving sexual dysfunction, which has no side effects on the human body, is easy to use, and has an excellent effect of fundamentally preventing and treating sexual dysfunction.

The present invention relates to a composition for improving sexual dysfunction comprising at least one 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 may include preferably 1 to 80% by weight, more preferably 5 to 60% by weight based on the total weight of the composition in terms of magnesium content of at least one or more components selected from the group consisting of magnesium compounds and magnesium salts have. In addition, when the composition of the present invention further comprises L-arginine or ginseng alcohol extract, or L-arginine and ginseng alcohol extract with the magnesium component, L-arginine is 1 to 80% by weight of the total weight of the composition, ginseng alcohol extract It is preferable to include 1 to 80% by weight of the total weight of the composition; L-arginine is more preferably 5 to 50% by weight of the total weight of the composition, ginseng alcohol extract is 2 to 50% by weight of the total weight of the composition.

Magnesium is one of the major electrolytes required by all cells in the body, and it is essential for maintaining muscle and nerve function, maintaining a constant heart rate and bone growth, as well as for energy metabolism and protein synthesis. (Wester PO.Magnesium.Am J Clin Nutr 1987; 45: 1305-12), magnesium deficiency is known to cause several diseases (Johnson S. The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses. 2001 56: 163-70).

The inventors have found that magnesium promotes the production and release of nitric oxide (NO) in the corpus cavernosum and clitoris cavernous bodies and applied it to the present invention. Therefore, the composition of the present invention has the effect of improving the sexual dysfunction by promoting the production and release of nitric oxide (NO) in the corpus cavernosum and clitoris cavernous body to relax the smooth muscle to increase the blood flow of the penis and clitoris.

Representative examples of magnesium compounds that may be included in the composition of the present invention include magnesium oxide, magnesium hydroxide, etc. Representative examples of magnesium salts are magnesium chloride, magnesium sulfate, magnesium gluconate, magnesium citrate, magnesium lactate, magnesium stearate, and the like. Can be mentioned. In particular, magnesium gluconate, magnesium citrate, magnesium lactate, magnesium oxide, and the like have more preferable effects.

In the present invention, as well as inducing the expression of L-arginine and NOS used as a substrate of NO as well as magnesium compounds and magnesium salts, ginsenosides (Li Z, Niwa Y, Sakamoto S) known as active stimulants , Shono M, Chen X, Nakaya Y. Induction of inducible nitric oxide synthase by ginsenosides in cultured porcine endothelial cells. Life Sci. 2000; 67: 2983-9; Scott GI, Colligan PB, Ren BH, Ren J. Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide. The composition comprising ginseng alcohol extract containing Br J Pharmacol 2001,134: 1159-65) exhibits an excellent effect on improving sexual dysfunction, in which case the composition of each composition is combined in an amount that exhibits a synergistic effect without side effects. It is important.

Excessive use of each composition can cause side effects such as decreased palatability and loss of erectile dysfunction. In the present invention, in order to significantly improve the composition of each material required for the synthesis and the synthesis of NO to reduce the capacity and very effectively increase the relaxation of the cavernous body by NO, was configured to enhance the effect as a sexual dysfunction improver.

Since one of the characteristics of the composition of the present invention includes magnesium salts known to prevent diabetes, cardiovascular diseases including hypertension and aging, which are the root causes of sexual dysfunction, the peripheral blood circulation is improved to fundamentally improve sexual dysfunction and such It has the effect of preventing and treating diseases.

In the composition of the present invention, the ginseng alcohol extract is dried ginseng in 1 ~ 10 times the weight of ethanol or a mixed solvent of ethanol and water and extracted for 1 to 10 hours at a temperature of 20 ~ 78 ℃, the filtrate is concentrated and lyophilized Get it.

The composition for improving sexual dysfunction of the present invention may be formulated in various forms when it contains a pharmaceutically acceptable carrier, excipient, and / or additive. That is, the composition according to the present invention may be formulated in the form of parenteral formulations, such as oral formulations such as conventional tablets, capsules, liquids, injections, transdermal administrations and the like. Examples of transdermal administration agents include creams, gels, ointments, lotions, and the like.

In addition, the composition of the present invention can be used in various foods. Examples of the food to which the composition of the present invention may be added include, for example, tea and health supplement foods.

The dosage of the composition of the present invention can be administered usually from 0.001 to 3 g / 1 based on the magnesium content or magnesium salt contained in the composition in terms of magnesium content.

Hereinafter, the specific configuration and operation of the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited by these examples and experimental examples.

Example 1 Preparation of Ginseng Alcohol Extract

1 kg of dried 4-year-old white ginseng was added to 3 L of 70% ethanol, and extracted by heating for 5 hours, filtered, the filtrate was concentrated, and the concentrate was lyophilized.

Formulation Example 1 Tablet

Magnesium Gluconate 400.0 mg

Lactose BP 250.0 mg

Starch BP 30.0 mg

Pregelatinized Corn Starch BP 15.0 mg

1.0 mg magnesium stearate

Magnesium gluconate was mixed with lactose, starch and pregelatinized corn starch, then a suitable volume of purified water was added and granulated into a powder. The granules were dried and then mixed with magnesium stearate and compressed to prepare tablets.

Formulation Example 2: Tablet

Magnesium Gluconate 200.0 mg

L-arginine 200.0 mg

Ginseng Alcohol Extract 100.0 mg

Lactose BP 250.0 mg

Starch BP 30.0 mg

Pregelatinized Corn Starch BP 15.0 mg

1.0 mg magnesium stearate

Magnesium gluconate, L-arginine and ginseng alcohol extracts were mixed with lactose, starch and pregelatinized corn starch, then a suitable volume of purified water was added and granulated into powder. The granules were dried and then mixed with magnesium stearate and compressed to prepare tablets.

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 then filled into gelatin capsules to prepare capsules.

Formulation Example 4 Capsule

Magnesium Gluconate 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 gluconate, L-arginine and ginseng alcohol extracts were mixed with starch and magnesium stearate, and then filled into gelatin capsules to prepare capsules.

Formulation Example 5: Injection

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 Up to 2ml

Magnesium gluconate, L-arginine and ginseng alcohol extracts were dissolved in a suitable volume of dilute sodium hydroxide solution, adjusted to pH 7.5-8.5, followed by volume adjustment using sodium chloride BP for injection and thoroughly mixing. The solution was filled into a 2 ml type ampoule of clear glass, filled under dissolution of the glass by dissolving the glass and then sterilized in a toclave to prepare an injection.

Formulation Example 6: Cream formulation

Furtherance

Magnesium Gluconate 30.0 wt%

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 flavor 0.1 0.1

Purified water level

quite

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

(2) Magnesium gluconate, L-arginine, ginseng alcohol extract, propylene glycol, citric acid, ketrol f, and purified water are dissolved by heating to 75 ℃.

(3) Put (1) into (2) and emulsify while mixing and stirring.

(4) Add ethanol and floral musk flavor during emulsification.

(5) A cream is prepared by cooling to 30 ° C or lower.

Formulation Example 7 Gel Formulation

Furtherance

Magnesium Gluconate 30.0 wt%

L-arginine 30.0 〃

Ginseng Alcohol Extract 13.0 〃

Carbopol 2 〃

Cetylethyl hexanoate 10 〃

Isostearic acid 2 〃

Polyoxyethylene sorbitan monostearate 5 〃

Ethanol 5 〃

Citric acid 0.3 〃

Sepigel 305 0.5 〃

Propylene Paraben 0.2 〃

Floral Musk flavor 0.1 0.1

Purified water level

quite

(1) Dissolve Carbopol sufficiently in purified water.

(2) Magnesium gluconate, L-arginine, ginseng alcohol extract, cetylethyl hexanoate, isostearic acid, polyoxyethylene sorbitan monostearate, ethanol, citric acid, propyl paraben, floral musk flavor To melt.

(3) Put the Sepigel 305 in the above (2) and mix and stir with a stirrer.

(4) A gel is prepared.

Experimental Example 1 Cavity Relaxation Effect Test

In the present invention, the tissue was prepared using New Zealand white rabbit of 2.5 to 3.0kg. Thiopental sodium (30 mg / kg) was injected into the rabbit's ear vein, followed by anesthesia, and the entire penis or clitoris was extracted from the pelvic bone, and only spongy body tissues were separated therefrom. At this time, care was taken not to forcibly manipulate the tissue to prevent endothelial damage present in the tissue. Tissue sections (1 × 2 × 7 mm) were obtained from the separated cavernous smooth muscle. Each section was secured at both ends using 6-0 threads, and then one was connected to a transducer to measure tension (transducer, Grass Research Polygraph, Model 79H, W. Warwick, RI), and the other to an organ tank ( fixed at the end of the organ bath). Avoid excessive pull to avoid damaging the endothelial tissue during fixation.

Penile cavernous tissues of male rabbits and clitoris sections of female rabbits were placed perpendicular to the 5 ml organ tank, and the tension in the tissues was recorded on a physiological recorder paper. The nutrient solution used was composed of NaCl 118 mM, KCl 4.7 mM, CaCl ₂ 2.5 mM, MgCl ₂ 2 mM, NaHCO ₃ 25 mM, glucose 10 mM, HEPES 10 mM, and titrated to 7.4 using 1N NaOH. It was. In addition, the nutrient solution was saturated with 100% oxygen, the temperature of the long-term tank was maintained at 37 ℃.

The tissue was initially adjusted to 1 g base tension, stabilized for about 60 minutes, and then started the experiment. The change in tension during the experiment was recorded on the physiological recorder paper. The drug was administered by accumulating from low concentration to high concentration, and the next concentration of drug was administered when the highest relaxation point was reached. When administering the new drug, it was washed three times with fresh nutrient solution and waited about 20 minutes to stabilize the tissue.

The expression of tension was based on the highest shrinkage point or the lowest relaxation point that occurred when the drug was administered. The contraction reaction by phenylephrine (PhE) and the relaxation reaction by acetylcholine (ACh) were observed to confirm that there was no endothelial cell damage, and the organ bath was washed with fresh nutrient solution. After contraction with PhE again, 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), magnesium gluconate (0.01) , 0.03, 0.1, 0.3, and 1 g / L) were administered at accumulative doses to observe the relaxation response. In addition, the relaxation effect of L-arginine (1 g / L) and ginseng alcohol extract (1 g / L) combined treatment group and L-arginine (1 g / L) and ginseng alcohol extract (1 g / L) and gluconic acid The relaxation effect of the group administered with magnesium (1 g / L) was compared. In addition, L-NAME ( ^10-3 M), a nitric oxide synthase inhibitor, was pretreated for 30 minutes and shrunk with PhE, followed by L-arginine (0.1 g / L) and ginseng alcohol extract (0.1 g / The relaxation effect of L) and magnesium gluconate (0.1 g / L) at the time of the compound administration was observed, and the relationship between the relaxation effect of the composite composition and the NO system was investigated.

Experimental responses to PhE and ACh showed a contraction response to PhE (10 ^-5 M) in the slices of all cases (PhCh, n = 22; clitoris, n = 25). In that shrinkage in PhE tissue ^10-5 tissues showing the relaxation response to ACh M is the penis were 22 cases, the clitoris was 25 cases. In addition, it was confirmed that the endothelial surrounding the cavernous space was not damaged from the relaxation reaction by ACh.

Experimental results, as shown in Figure 1, 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), respectively , 0.03, 0.1, 0.3 and 1 g / L) showed dose-dependent penile cavernous relaxation and were repeatedly observed. In particular, 1 g / L of L-arginine or magnesium gluconate showed a similarly strong relaxation effect on the relaxation effect of 10 uM Ach. In addition, 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 and 0.3) were also used in the clitoris. And 1 g / L) showed a dose-dependent penile cavernous relaxation response (FIG. 2). Interestingly, as shown in Fig. 3, the relaxation effect of the L-arginine (1 g / L) and ginseng alcohol extract (1 g / L) combination group was significantly increased in the presence of magnesium gluconate (1 g / L). Enhancement was observed. In addition, L-arginine (0.1 g / L), ginseng alcohol extract (0.1 g / L) and magnesium gluconate (0.1 g / L) when pre-treated with L-NAME (10 ^-3 M) for 30 minutes The relaxation effect of the composition was markedly blocked (FIG. 4). These experimental results strongly suggest that the relaxation effect of the composite composition is via the NO system.

As described above, the present invention provides a composition for improving sexual dysfunction, which is excellent in the effect that can be easily prevented and treated sexually dysfunction without any side effects on the human body.

Figure 1 shows the corpus cavernosum relaxation effect according to the administration concentration of L-arginine, ginseng alcohol extract and magnesium gluconate, respectively.

Figure 2 shows the clitoris cavernous relaxation effect according to the administration concentration of L-arginine, ginseng alcohol extract and magnesium gluconate, respectively.

Figure 3 shows a comparison of the corpus cavernosum relaxation effect of the L-arginine treatment group, the combined treatment group of L-arginine and ginseng alcohol extract and the combined treatment group of L-arginine, ginseng alcohol extract and magnesium gluconate.

Figure 4 is a pretreatment of the cavernous tissue with L-NAME (10 ^-3 M), a nitric oxide synthase inhibitor, and the degree of blocking the corpus cavernosum relaxation effect when L-arginine, ginseng alcohol extract and magnesium gluconate were administered in combination It is shown in comparison with the control.

Claims (7)

Composition for improving sexual dysfunction comprising at least one component selected from the group consisting of magnesium compounds and magnesium salts. According to claim 1, L- arginine or ginseng alcohol extract, or L- arginine and ginseng alcohol extract, characterized in that it further comprises a composition for improving sexual dysfunction. The magnesium compound is selected from 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. Composition for improving sexual dysfunction. The composition for improving sexual dysfunction according to claim 1, wherein at least one or more components selected from the group consisting of magnesium compounds and magnesium salts are contained in an amount of 1 to 80 wt% based on the total weight of the composition. The composition for improving sexual dysfunction according to claim 2, comprising 1 to 80% by weight of L-arginine and 1 to 80% by weight of ginseng alcohol extract. The ginseng alcohol extract is dried ginseng 1-10 times the weight of ethanol or a mixed solvent of ethanol and water and extracted for 1-10 hours at a temperature of 20 ~ 78 ℃, the filtrate is concentrated and frozen Composition for improving sexual dysfunction, characterized in that obtained by drying. Food comprising the composition of claim 1.