KR101241050B1 - Composition containing ginseng berry extract for improving sexual function - Google Patents

Abstract

The present invention relates to a composition for improving sexual function in males containing ginseng fruit extract, and more particularly, the composition of the present invention increases the production of nitric oxide (NO) in vascular endothelial cells by containing ginseng fruit extract as an active ingredient. It is possible to relax the corpus cavernosum smooth muscle to improve male sexual function through the enhancement of penis erection, and also to produce nitrogen monoxide by simultaneously using L-arginine, which is a substrate of nitric oxide synthase The effect can be further enhanced.

Description

Composition containing ginseng berry extract for improving sexual function}

The present invention relates to a composition for improving sexual function in men containing a ginseng fruit extract as an active ingredient, and more specifically, by containing a ginseng fruit extract having a different ingredient and composition from ginseng root in the ground of ginseng as an active ingredient, vascular endothelial cells. It relates to a composition for improving male sexual function through the enhancement of the erection of the penis to relax the corpus cavernosum smooth muscle by showing the effect of increasing the production of nitric oxide (NO) in.

Ginseng (Panax ginseng CA Meyer) is a plant belonging to the genus Ogapiaceae ginseng, which has been used in Korea, China, and Japan for more than 2,000 years, and has been used to prevent disease and extend life. The effects and effects of ginseng on the central nervous system, anti-carcinogenic, anti-cancer, immune-modulatory, anti-diabetic, hepatic anti-inflammatory effect, cardiovascular disorders, anti-arteriosclerosis, blood pressure control, menopausal disorders , Effects on osteoporosis, antistress action, anti-fatigue, antioxidant activity and anti-aging effects are known (latest ginseng 'components and efficacy', Korea Ginseng and Tobacco Research Institute, 56-112, 1996).

Ginsenoside, a representative physiologically active ingredient of ginseng, is distributed evenly in the ground and underground parts of ginseng. Especially, ginsenoside content and composition are different depending on the parts such as ginseng root (root), ginseng leaf and ginseng fruit. (Attele AS et al, Biochem Pharmacol, 58; 1685-1693, 1999). Among them, ginseng berry has the content and composition of ginsenoside and other ginsenosides, and it has been reported that the ginseng fruit has better results than ginseng root in antidiabetic effect (Dey L. et al., Phytomedicine , 10; 600-605, 2003).

L-arginine is a basic amino acid having the formula C ₆ H ₁₄ N ₄ O ₂ , having a molecular weight of 174.21, isolated from the sprouting of lupine. L-arginine exists as one of the amino acids constituting the protein, belongs to the protein protamine in fish sperm and is free in plant seeds. In addition, as a metabolic pathway in vivo, it is a component of the uric acid production pathway (ornithine cycle), and is broken down into urea and ornithine by the action of arginase. Produced from citrulline and aspartic acid, it is a non-essential amino acid for adults but an essential amino acid for infants.

NO-nitro-L-arginine is known to be an inhibitor of nitric oxide (NO) synthase, and there is research showing that NO-nitro-L-arginine can interfere with blood vessel relaxation. However, studies have shown that the inhibitory effects of NO-nitro-L-arginine can be reversed in the presence of L-arginine (3 × 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. 92: 3, 265-75). The study suggests that L-arginine can be an effective substrate for nitric oxide synthase and can stimulate nitric oxide release in blood vessels.

Male sexual function is composed of sexual desire, erection of the penis, ejaculation and extreme sensation, which is determined by the complex physiological reactions of the nervous system, endocrine system and vascular system. Most of the sexual dysfunction was considered to be a psychogenic cause only a decade ago, but due to the development of modern medicine, about 50% of patients with sexual dysfunction are caused by various causes such as vascular, nervous and endocrine diseases, diabetes, hypertension, and drug use. It turns out. Recently, sildenafil, a phosphodiesterase V inhibitor, has attracted much attention in the treatment of sexual dysfunction, but such treatment is a method of causing temporary erection using chemicals, and has a high price, headache, and increased blood pressure. There are many side effects such as heart attack. In particular, a number of deaths due to aggravating heart disease have been reported. Therefore, a safe and effective treatment for sexual dysfunction that enhances the body's instinctive erectile function should be developed, and the recent trend is to increase the production of nitric oxide and cGMP, which are strong signaling agents in the cavernous smooth muscle, penis. There is a growing interest in developing therapeutics for sexual function that enhances the erection of cavernous bodies.

The changes that occur during the penile erection process are complex and require a high degree of integrated control involving the peripheral and central nervous and endocrine systems. Cavernous smooth muscle contraction is regulated by sympathetic noradrenergic nerve stimulation through activation of α1 adrenergic receptors after synapses, and erectile dysfunction may be associated with an increase in the endogenous smooth muscle tension of the cavernous body. However, the process of penile smooth muscle relaxation is partially mediated by non-drenergic, noncholinergic (NANC) neurotransmission, and the decrease in the tension of the corpus cavernosum smooth muscle is because nitrogen monoxide induces the relaxation of the corpus cavernosum. During sexual arousal, nitric oxide is released from neurons and endothelium and binds to and activates soluble guanylate cyclase (sGC) located in smooth muscle cells and endothelium, thereby intracellular cyclic guanosine 3'-, 5'-monophosphate raises cGMP levels. Increase of the cGMP level is the protein kinase G thought that activation is involved, but, unknown mechanism due to a decrease in intracellular calcium concentration cell with the (Ca ^{2 +} - Likely to be due to the activation of the channel-activated K ⁺⁾ cavernosum Induce relaxation (Chuang et al., CGMP mediates corpus cavernosum smooth muscle relaxation with altered cross-bridge function.Life Sci. 1998; 63 (3): 185-94).

Therefore, the combination of L-arginine, a substrate of nitric oxide synthase, and a substance that promotes the production of nitric oxide (NO) in blood vessels stimulates the release of nitrogen monoxide in the cavernous body, causing and sustaining smooth muscle relaxation. It will be a great advantage in that it can induce and reduce erectile dysfunction.

Accordingly, the present inventors found that the ginseng fruit extract has a male sexual function-improving effect by different ingredients and compositions from general ginseng and red ginseng, while studying various physiological activities of ginseng fruit extracts in the ground part as well as ginseng root which is the underground part of ginseng. In addition, it was found that the effect is increased when used in combination with L-arginine, a substrate of nitric oxide synthase, and completed the present invention.

Accordingly, it is an object of the present invention to provide a composition for improving male sexual function through an increase in the erection of the penis by exhibiting an effect of increasing the production of nitric oxide (NO), which is a signaling material showing a strong relaxation effect in the smooth muscle of the corpus cavernosum.

In order to achieve the above object, the present invention provides a composition for improving male sexual function containing a ginseng fruit extract as an active ingredient.

The present invention also provides a composition for improving male sexual function, further comprising L-arginine in the ginseng fruit extract active ingredient.

Ginseng fruit extract of the present invention increases the production of nitric oxide (NO) in vascular endothelial cells, suggesting the possibility of promoting the erection of the penis by the production of nitric oxide (NO). This effect may also be elevated when used in combination with L-arginine, a substrate of nitric oxide synthase. Therefore, the composition containing ginseng fruit extract and L-arginine as an active ingredient may provide a male sexual function improving effect.

1 is a graph showing the results of analyzing ginsenoside components of ginseng fruit extract (Example 1) and ginseng root extract (Comparative Example 1).
Figure 2 shows a photograph taken with a confocal laser microscope of the effect of promoting the production of nitric oxide (NO) in the vascular endothelial cells of L-arginine, red ginseng extract and ginseng fruit extract.
3 is a graph showing the relative fluorescence intensity of the effect of promoting the production of nitric oxide (NO) in vascular endothelial cells of L-arginine, red ginseng extract and ginseng fruit extract.
Figure 4 is a graph showing the relative fluorescence intensity synergistic effect of nitric oxide production of ginseng fruit extract and L-arginine.

The present invention contains a ginseng fruit extract as an active ingredient in order to provide a composition for improving male sexual function by enhancing the erection of the penis through the effect of increasing the production of nitric oxide (NO) in vascular endothelial cells, wherein L-arginine It may contain more.

In order to improve male sexual function, it is necessary to promote penile erection by showing strong relaxation in the corpus cavernosum smooth muscle. The mechanism of action is focused on increasing the production of nitrogen monoxide (NO). In this connection, nitric oxide has been shown to play an important role in penile erection in animal experiments. The production of nitric oxide secreted by vascular endothelial cells is also increased in the parasympathetic peripheral of the penis under sexual stimulation. Nitrogen monoxide activates guanylate cyclase to convert guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). The cGMP generated here induces erection of the penis by providing a signal that causes relaxation of the cavernous smooth muscle and penile artery. Therefore, the production of nitric oxide is important in order to sustain penile erection.

The male sexual function improving composition according to the present invention is characterized in that the ginseng fruit extract is mixed in an amount of 0.01 to 100% by weight based on the total weight of the composition. In addition, when used in combination with L-arginine, L-arginine may be used in a ratio of 0.01 to 99.9% by weight based on the total weight of the composition.

In addition, the composition may be formulated as a pharmaceutical composition or food composition in the form of tablets, pills, tablets, capsules, granules, powders, ointments, drinks or injections.

The compositions of the present invention can be prepared in pharmaceutical formulations according to conventional methods. In the preparation of the formulations, it is preferred that the active ingredient is mixed with or diluted with the carrier, or enclosed in a carrier in the form of a container. When the carrier is used as a diluent, it may be a solid, semisolid or liquid substance which acts as a carrier, excipient or medium for the active ingredient. Thus, the formulations may be in the form of tablets, pills, powders, assays, elixirs, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, sterile injectables, sterile powders and the like.

Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydride Oxybenzoate, talc, magnesium stearate and mineral oil. The formulations may additionally include fillers, anti-coagulants, lubricants, wetting agents, perfumes, emulsifiers, preservatives, and the like. Compositions of the present invention may be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal.

The pharmaceutical composition of the present invention may be administered through several routes including oral, transdermal, subcutaneous, intravenous, abdominal, muscle, topical application, patch and iontophoresis, of which topical application and oral administration are preferred. Do.

In humans, a typical daily dosage of the active compound may range from 1 to 100 mg / kg body weight, preferably 5 to 70 mg / kg body weight, and may be administered once or in several doses. However, it should be understood that the actual dosage of the active ingredient should be determined in light of several relevant factors such as the disease to be treated, the route of administration, the age, sex and weight of the patient, and the severity of the disease, and therefore the dosage may be determined in any way. Nor does it limit the scope of the present invention.

Hereinafter, the present invention will be described in detail with reference to Examples, but the technical scope of the present invention is not limited to these Examples.

Example 1 Preparation of Ginseng Fruit Extract

1. Ginseng Fruit Pretreatment

Raw ginseng fruit was harvested, seed was separated and removed, and then the ginseng fruit dried raw material was prepared by sun drying or hot air drying.

2. Ginseng Fruit Extract Manufacturer

Water or alcohol 3 L was added to 1 kg of dried ginseng fruit dried, followed by extraction at room temperature or reflux, followed by filtration and concentration under reduced pressure at 40 to 45 ° C. to obtain 300 g of ginseng fruit extract.

Comparative Example 1 Preparation of Ginseng Root Extract

Except for using ginseng root (root) instead of ginseng fruit in Example 1 was prepared in the same manner as in Example 1.

Test Example 1 Component Comparison of Ginseng Fruit Extract

<Analysis of Ginsenoid (Ginseng Saponin) in Ginseng Fruit and Ginseng Root>

In Example 1 and Comparative Example 1, respectively, ginseng fruit and ginseng root extract were prepared, and these extracts were treated with ether to remove fat-soluble components, followed by extracting and concentrating irradiated with butanol (BuOH), using HPLC. Noid component analysis was performed, and the results are shown in FIG. 1 and Table 1 below.

Example 1 Comparative Example 1 Irradiated Ponin Content (Dry Weight) 33.42% 16.70% PD / PT ratio 0.73 3.23

1 and Table 1, the ginseng fruit extract prepared in Example 1 has about 2 times the content of the ginseng root extract prepared in Comparative Example 1 in the content of irradiated phonoins, ginsenoside PD (Protopanaxadiol) Ginseng fruit and ginseng in the composition of 0.73 and 3.23, respectively, when divided into the ratios of "-ginsenoside Rb1, Rb2, Rc and Rd" and PT (Protopanaxatriol)-"ginsenoside Re, Rg1 and Rg2" It can be seen that the roots exhibit distinct differences and features.

Mineral Analysis of Ginseng Fruit Extract

In order to distinguish that the ginseng fruit extract prepared in Example 1 has the characteristics of "fruit" different from ginseng, mineral components including vitamins were analyzed, and the results are shown in Table 2 below.

ingredient content ingredient content Potassium (mg / 100g) 5865.57 Magnesium (mg / 100g) 354.38 Calcium (mg / 100g) 819.26 Zinc (mg / 100g) 178.49 Iron (mg / 100g) 59.31 Vit.A (ug / 100g, RE) 213.11 Phosphorus (mg / 100g) 187.17 Vit.B1 (mg / 100g) 12.29 Vit.B2 (mg / 100g) 8.45 Vit.B6 (mg / 100g) 10.50 Vit.C (mg / 100g) 4.91 Vit.E (mg / 100g, α-TE) 23.61 Vit.K (μ / 100g) 232.12 Niacin (mg / 100 g, NE) 5.76 Pantothenic Acid (mg / 100g) 5.87 Folic Acid (µg / 100g) 349.97

As described above, the ginseng fruit used in the present invention contains more ginseng saponin than the ginseng root, and at the same time, the nature of the composition of saponin is opposite to that of the ginseng root. Could confirm.

Based on the results, the effect of ginseng fruit extract on male reproductive function was tested. As a comparison material, red ginseng extract, which is widely used as a health food with the expected effect of improving male sexual function, was compared with ginseng fruit extract.

Comparative Example 2 Preparation of Red Ginseng Extract

Red ginseng extract was prepared to compare the efficacy with the ginseng fruit extract. Water or alcohol 6-6 L was added to 1 kg of red ginseng (14% water content) or red ginseng powder, followed by extraction at room temperature / reflux three times, followed by filtration and concentrated under reduced pressure to obtain 250 g of red ginseng extract. .

Experimental Example 2 Effect of Ginseng Fruit Extract on the Production of Nitric Oxide (NO) in Endothelial Cells

When ginseng fruit extract was treated with vascular endothelial cells, the production of nitric oxide (NO), which is an important signaling material for penile erection, was observed. This is because increased production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) in vascular endothelial cells can relax blood vessels and promote penile erection.

The specific experimental method is as follows.

1. Isolation and Culture of Endothelial Cells from Umbilical Cord

Endothelial cells exist on the basement membrane of blood vessels, and are cells which are located at the innermost side of blood vessels and are in direct contact with blood. There are various types of endothelial cells, among which the most widely isolated and used cells include human umbilical vein endothelial cells (HUVECs).

In order to separate HUVECs, the veins in the umbilical cord (15-20 cm) were first washed well with PBS to remove blood coagulants. Next, cannular and 2-way stop cocks were installed at both ends of the umbilical vein tube, and 250 units / ml of collagenase was injected and incubated at 37 ° C. for 5 to 10 minutes. HUVECs were separated from the basement membrane by activity. Endothelial cells (HUVECs) obtained from human umbilical veins (20% (w / v) FBS, 100 units / ml penicillin, 100 μg / ml streptomycin, 3 ng / ml basic fibroblast growth factor) and 5 Transfer to plates and flasks coated with gelatin using M199 medium containing units / ml of heparin at 37 ° C., 5% CO ₂ Lt; / RTI &gt;

2. Measurement of nitric oxide production in vascular endothelial cells (HUVEC)

Vascular endothelial cells were cultured at a density of 2.5 × 10 ⁴ cells / well in a gelatin coated 24 well plate incubator, and the cells were incubated for 12 hours in growth medium. Vascular endothelial cells were pretreated at a concentration of 100 μg / mL for 12 hours, divided into control group, L-arginine treatment group, red ginseng extract (RG) treatment group of Comparative Example 2, and ginseng fruit extract (GB) treatment group of Example 1. Endothelial cells were treated for 30 minutes with 10 μmol / L DAF-FM diacetate (Molecular Probe, OR) in M199 medium without FBS at 37 ° C. Vascular endothelial cells were washed three times with M199 medium without FBS, placed in a parallel plate flow chamber, and stimulated with light separated from a mercury lamp. The excitation wavelength was 488 nm, and DAF bound with nitric oxide (NO) fluoresced at 515 nm. Photos are taken with a confocal laser microscope (Atto Bioscience, USA), and the fluorescence brightness is measured with image-Pro Plus v4.5 software (Media Cybernetics, San Diego, CA, USA). This was shown in Figures 2 and 3. In Figures 2 and 3 con is a control group, RG is a red ginseng extract treatment group of Comparative Example 2, GB means a ginseng fruit extract treatment group of Example 1, RG 50 is a red ginseng extract 50 ㎍ / ml, RG 100 is red ginseng Extract 100 ㎍ / ml, L-arginine 250 is L-arginine 250 μM, L-arginine 500 is L-arginine 500 μM, GB 50 is ginseng fruit extract 50 ㎍ / ml, GB 100 is 100 ug / ml It means to process.

As shown in Figures 2 and 3, the treatment of ginseng fruit extract showed a significant increase in nitric oxide (NO) in the vascular endothelial cell (HUVEC) monolayer culture system compared to the control group This effect was concentration dependent. In the red ginseng control group, the production of nitric oxide (NO) was increased about 1.5 times compared to the control group at 100 ㎍ / ml, and L-arginine, a substrate of nitric oxide synthase, was 2.7-fold and 250-micron at 500 μM On the other hand, the ginseng fruit extract increased the production of nitric oxide (NO), a signaling substance for vasorelaxation at concentrations of 50 μg / ml and 100 μg / ml by 4 and 12 times, respectively, compared to the control. That is, the effect of ginseng fruit extract was the best, and when compared with the efficacy of red ginseng extract, it was found to be about 8 times more effective than the red ginseng extract at the concentration of 100 ㎍ / ml.

Ingestion of ginseng fruit extract from the above results, it can be seen that since the production of nitric oxide (NO) in the vascular endothelial cells, it is possible to promote penile erection due to vasodilation in the corpus cavernosum.

Test Example 3 Synergistic Effects of Nitric Oxide Production When Ginseng Fruit Extract and L-Arginine Combined

When the ginseng fruit extract promoting the production of L-arginine and nitrogen monoxide (NO), which are known as substrates of nitric oxide synthase, was simultaneously treated, it was observed whether the production of nitric oxide was elevated.

Endothelial cells were isolated and cultured from the umbilical cord, and production of nitric oxide (NO) in the cultured vascular endothelial cells was measured. Specific experimental method is the same as in Test Example 2, the results are shown in FIG.

In Figure 4 con means a control, L-arginine 500 L- arginine 500 μM, GB 100 is 100 ㎍ / ml ginseng fruit extract, L-arginine + GB is L- arginine 500 μM + 100 g / ginseng fruit extract It means to treat ml.

As shown in FIG. 4, 100 g / ml of ginseng fruit extract and 500 μM of L-arginine were simultaneously treated with vascular endothelial cells, indicating that the production of nitric oxide (NO) was much higher than that of each treatment. This can be seen as a synergy effect.

From the above results, the mixed prescription of L-arginine and ginseng fruit extract, which are the substrates of nitric oxide-producing enzymes, dramatically increases the production of nitrogen monoxide. Therefore, the mixed prescription of ginseng fruit extract and L-arginine relaxes the corpus cavernosum. It can be seen that by inducing and sustaining can be a great help in improving male sexual function.

Claims (5)

Male erectile dysfunction treatment pharmaceutical composition containing ginseng fruit extract as an active ingredient. The pharmaceutical composition for treating male erectile dysfunction according to claim 1, wherein the composition further comprises L-arginine. The pharmaceutical composition of claim 1, wherein the composition contains ginseng fruit extract in an amount of 0.01 to 100% by weight based on the total weight of the composition. The pharmaceutical composition for treating male erectile dysfunction according to claim 2, wherein the composition contains L-arginine in an amount of 0.01 to 99.9 wt% based on the total weight of the composition. The pharmaceutical composition for treating male erectile dysfunction according to claim 1, wherein the ginseng fruit extract is prepared by extraction with water or alcohol.

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