KR20030088906A - A composition for treating sexual dysfunction comprising an extract from sophora flavescenes and compounds isolated therefrom - Google Patents

Abstract

PURPOSE: Provided is a composition for treating sexual dysfunction which contains a flavonoid compound represented by the formula 1 or 2, and an extract of Sophora flavescens containing them, as active ingredients. The composition inhibits on cGMP-PDE5 and is thus useful for the prevention and treatment of sexual disfunction. CONSTITUTION: A composition for treating sexual dysfunction is characterized by containing, as active ingredients, a flavonoid compound represented by the formula 1 or 2, wherein R1 is a unsubstituted or hydroxy group-substituted linear or branched alkenyl group; R2 is hydrogen, hydroxy or C1-C3 alkoxy; R3 and R4 are individually hydrogen or a hydroxy group; and a dotted line represents single or double bond, and its pharmaceutically acceptable salt, hydrates, solvate, isomer or their mixture.

Description

A composition for improving sexual dysfunction comprising a extract of Ginseng {A COMPOSITION FOR TREATING SEXUAL DYSFUNCTION COMPRISING AN EXTRACT FROM SOPHORA FLAVESCENES AND COMPOUNDS ISOLATED THEREFROM}

The present invention relates to a composition for improving sexual dysfunction, including a ginseng extract, and more particularly, having an inhibitory activity of cGMP (cyclic guanosine monophosphate) phosphodiesterase, which can be used to improve sexual dysfunction such as erectile dysfunction. It relates to a flavonoid compound or a composition for improving sexual dysfunction, containing a ginseng extract comprising the same as an active ingredient.

Erectile dysfunction or impotence is defined as the lack of sexual intercourse in men and includes inability to penile erection or ejaculation. Specifically, erectile dysfunction or erectile dysfunction is a case in which there is not enough erection to maintain sexual activity, or even if the erection is not maintained, it is known that 2-7% of the male population has this symptom, 50 years or less It is known that 18-75% of the ages between 55 and 80 years have increased. For example, it is estimated that there are fewer than 10 million men with erectile dysfunction in the United States alone, most of them due to temperament (physical causes) rather than psychogenic (mental causes).

In the mechanism of erection, when sexual stimulation is transmitted, a body component called cyclic guanosine monophosphate (cGMP) is specifically created around the arteries of the penis, which causes the arteries to expand and the blood collects and hardens into the corpus cavernosum. cGMP expands the corpus cavernosum, narrowing the spacing between the sponges, preventing blood from entering the arteries into the veins, resulting in less blood leaking out, leading to a larger penis and erection. The remaining cGMP after erection is broken down by PDE5 (phosphodiesterase-5), which is an enzyme that releases the erection and returns to its original state.

Sildenafil, which has been recently developed and used worldwide as a therapeutic agent for erectile dysfunction, increases the concentration of cGMP by inhibiting PDE5, which is specifically distributed in the corpus cavernosum. Although it is known that there are a number of side effects such as headache, hot flashes, indigestion and heart attack have been reported, there is a need for a new medicine that can replace or supplement. Therefore, in the art, researches for synthesizing cGMP-PDE5 inhibitors having better pharmacological action than sildenafil and researches for developing erectile dysfunction using natural products are introduced.

In Korean Patent No. 079869, a combination preparation of L-alanine, prickly pear extract, and goji berry extract has been disclosed for the treatment of erectile dysfunction. However, conventional studies on the treatment of erectile dysfunction from natural products do not suggest a mechanism of action to prove effective as erectile dysfunction, such as sildenafil, or ingredients effective in treating erectile dysfunction in these combinations.

Sophora flavescens , which has been used as a high-density agent, peripheral vasoconstrictor, antipyretic analgesic and parasitic parasites, uses the root as a herbal medicine as Sophorae radix . The main active ingredients of ginseng are alkaloids such as matrine and oxymatrine. Flavonoids include kushenol H, kushenol K, and kura. Linar (kurarinol), kuraridine and the like are known. In addition, recently, the inventors have found that the structure of sophora flavesenol is first separated from red ginseng (Kim Hyung-ja et al., Journal of Natural Products , 1998, 61 (12), 1552). However, it has not been found that ginseng extract or ingredients contained in ginseng inhibit the inhibitory activity of cGMP-PDE5, which is expected to improve sexual dysfunction such as erectile dysfunction.

The inventors of the present invention, while researching a substance that strongly inhibits the activity of cGMP-PDE5 against a variety of herbal drugs to ensure human safety, while the extract of Sophora flavescenes strongly inhibits the activity of cGMP-PDE5 at a low concentration Found that Cushenol H, Cushenol K, Curalinol, Sophoflavesenol and Curaridin, which are obtained by separating and purifying the components contained in the extract of Ginseng, strongly inhibit the activity of cGMP-PDE5. The present invention was completed by revealing that it can exhibit an excellent effect on the improvement of sexual dysfunction.

An object of the present invention is to provide a composition for improving sexual dysfunction showing a strong inhibitory activity on cGMP-PDE5.

Specifically, it is an object of the present invention to provide a composition for improving sexual dysfunction using the compound represented by Formula 1 or Formula 2 as an active ingredient.

In addition, another object of the present invention to provide a composition for improving sexual dysfunction as an active ingredient ginseng extract.

It is another object of the present invention to provide a method for separating and purifying the compound represented by the formula (1) or (2) from the ginseng extract.

1 is a cGMP-PDE5 activity inhibitory of Cushenol H (△), Cushenol K (○), Curarinol (□), Sophoflavesenol (■) and Curaridine (▲) isolated from the ginseng extract of the present invention Effect,

Figure 2 is a Linewaever-Burk plot prepared by analyzing the effect on the PDE5 activity extracted from the diaphragm of the Kurarino rat of the present invention,

3 is a Linewaever-Burk plot prepared by analyzing the effect of the vesicle flavesense of the present invention on the PDE5 activity extracted from the diaphragm of the white paper,

Figure 4 shows the Linwaber-Burk plot prepared by analyzing the effect of the Kuraridine of the present invention on PDE5 activity extracted from the diaphragm of the white paper.

In order to achieve the above object, the present invention has a cGMP-PDE5 inhibitory activity to extract a flavonoid compound or ginseng extract represented by the following formula (1) or (2) which can be used to improve sexual dysfunction, such as erectile dysfunction or erectile dysfunction It relates to a composition for improving sexual dysfunction containing as an active ingredient.

(In the above formula,

R ₁ is a C ₅ to C ₁₁ straight or crushed alkenyl group which is unsubstituted or substituted with a hydroxy group,

R ₂ is hydrogen, hydroxy or alkoxy of C _{1 to} C ₃ ,

R ₃ and R ₄ are each independently hydrogen or hydroxy,

Dotted lines indicate single bonds or double bonds.)

Preferred compounds among the compounds of Formulas 1 and 2 are shown below.

(1) 2- (2,4-Dihydroxy-phenyl) -3,7-dihydroxy-8- [2- (3-hydroxy-3-methyl-butyl) -3-methyl-but-3 -Enyl] -5-methoxy-chroman-4-one (Cushenol H, Formula 3)

(2) 2- (2,4-Dihydroxy-phenyl) -3,7-dihydroxy-8- [2- (3-hydroxy-3-methyl-butyl) -3-methyl-but-3 -Enyl] -5-methoxy-chroman-4-one (Kuschenol K, Formula 4)

(3) 2- (2,4-dihydroxy-phenyl) -7-hydroxy-8- [2- (3-hydroxy-3-methyl-butyl) -3-methyl-but-3-enyl] -5-methoxy-chroman-4-one (curanol, formula 5)

(4) 3,7-dihydroxy-2- (4-hydroxy-phenyl) -5-methoxy-8- (3-methyl-but-2-enyl) -chromen-4-one (vesoplast Besenol, formula 6)

(5) 1- [2,4-Dihydroxy-3- (2-isopropenyl-5-methyl-4-hexenyl) -6-methoxy-phenyl] -3- (2,4-dihydro Roxy-phenyl) -propenone (curaridine, formula 7)

Since the compounds may have asymmetric carbon centers in their structure, they may exist as individual enantiomers or diastereomers, as well as mixtures thereof including racemates. Such isomers or mixtures thereof are also included in the scope of the present invention.

The compounds according to the invention can also form pharmaceutically acceptable salts. These pharmaceutically acceptable salts include alkali metal hydroxides (e.g. sodium hydroxide, potassium hydroxide), alkali metal bicarbonates (e.g. sodium bicarbonate, potassium bicarbonate), alkali metal carbonates (e.g. sodium carbonate, potassium carbonate, calcium carbonate), and the like. The same inorganic base and organic base such as primary and secondary tertiary amine amino acids are included.

The compounds of the invention may also be in the form of solvates, in particular hydrates. Hydration may occur during separation of the compound, or may occur over time due to the hygroscopicity of the compound.

The extract of red ginseng having an effect of improving erectile dysfunction by having cGMP-PDE5 inhibitory activity of the present invention is obtained by extracting with C ₁ -C ₄ lower alcohol, hydrous alcohol, dichloromethane or ethyl acetate, followed by filtration and evaporation under reduced pressure. Further, the gourd alcohol extract obtained by extracting with C _{1 to} C ₄ lower alcohol is filtered and evaporated under reduced pressure, and then the solution suspended in water is extracted with dichloromethane, ethyl acetate or butanol and then filtered and evaporated under reduced pressure. For example, the roots of red ginseng are finely chopped or powdered and used as it is or lyophilized, and then 0.1-5 L of a lower alcohol such as methanol and ethanol, an aqueous solution of 60-100% alcohol of the lower alcohol, per 1 kg, Preferably it is added in the amount of 0.5-1.0 L and it is left to stand at room temperature for 4 to 5 days. The process may be repeated three or more times as necessary. The extract obtained is filtered and evaporated under reduced pressure to give an alcohol extract. Further, 1 to 5 L, preferably 1.5 to 2.0 L, of water per kg of alcohol extract is added, followed by sufficient extraction with 0.1 to 5 L of ethyl acetate (EtOAc), preferably 1.0 to 1.5 L, to obtain an ethyl acetate extract. Can be. The ethyl acetate extract may be prepared by omitting the alcohol extraction process and extracting the root of the ginseng directly with ethyl acetate.

In order to confirm the improvement effect of sexual dysfunction such as erectile dysfunction of the flavonoid compound of the present invention, as a result of investigating cGMP-PDE5 activity, as shown in Figure 1 , Cushenol H, Cushenol K, Curanol, Sophoflave All five flavonoid compounds, senol and curaridine, inhibited cGMP-PDE5 activity in a concentration-dependent manner. Analysis of PDE5 inhibitory mechanisms of curarinol, phosphoflavesenol, and curaridine, which have relatively high inhibitory effects, showed competitive or mixed activity inhibition (see FIGS. 2 to 4 ). These results show that the flavonoid compound of the present invention is effective in improving sexual dysfunction such as erectile dysfunction due to its excellent cGMP-PDE5 inhibitory effect.

In addition, it can be seen that methanol extract of ginseng exhibited an effect of strongly inhibiting the activity of cGMP-PDE5. Inhibition of cGMP-PDE5 activity of the extracts of methanol extract of Ginseng extract with dichloromethane, ethyl acetate, butanol, water, etc. was the most potent, followed by dichloromethane. Extract, and the inhibitory effect of butanol and water extracts on cGMP-PDE5 activity was generally weak.

As described above, in order to use the ginseng extract for the improvement of sexual dysfunction such as erectile dysfunction, alcohol solvent extracts such as methanol, ethanol and hydrous ethanol can be used, and the use of ethyl acetate or dichloromethane fraction is very effective pharmacological action. It can be seen that can be obtained.

As a result, the flavonoid compounds represented by Formula 1 and Formula 2 of the present invention and the ginseng extract containing the same inhibit the activity of cGMP-PDE5, and thus the composition of the present invention comprising them is for improving sexual dysfunction such as erectile dysfunction. It can be usefully used.

The compositions of the present invention can be administered in a variety of oral or parenteral formulations and can be used in the form of general pharmaceutical formulations. The pharmaceutical compositions of the present invention can be used to prepare pharmaceutical formulations according to conventional methods. In the preparation of the formulation, it is preferred to mix the active ingredient with the carrier, to dilute it with the carrier, or to enclose it in a carrier in the form of a capsule, assay or other container. Thus, the formulation may be a tablet, pill, powder, sasay, elixir, suspension, emulsion, liquid, syrup, aerosol, soft or hard gelatin capsule, injectable solution or suspension, ointment, cream, gel or lotion, etc. It may be in the form of.

Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, Propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The formulation may further comprise fillers, anti-coagulants, lubricants, wetting agents, fragrances, 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 dosage of the active ingredient according to the present invention is appropriately selected depending on the absorption rate, inactivation rate and excretion rate of the active ingredient in the body, the age, sex and condition of the patient, and the severity of the disease to be treated, but generally once a day It may be administered in several divided doses, and preferably, the compound may be formulated to be administered at a concentration of 10 to 1,000 mg / kg, more preferably 20 to 500 mg / kg, and an extract of 50 to 10,000 mg / kg. The exact amount, route of administration, and frequency of the agent can be readily determined according to the nature of the agent, the weight and condition of the subject to be administered, and the nature of the particular derivative to be used.

According to the present invention, the composition shows that the acute toxicity test in mice, the anti-lethal dose (LD ₅₀ ) upon oral administration or intraperitoneal injection shows no toxic effect at 10,000 mg / kg or more, thereby showing very high biosafety. Therefore, the composition for improving sexual dysfunction of the present invention can be safely administered to a living body.

In addition, the present invention includes a method for separating and purifying the compounds represented by the formula (1) and (2) from the ginseng extract.

Specifically, the present invention is performed by performing column chromatography on the ethyl acetate extract of Ginseng obtained above using a filler selected from the group consisting of silica gel, Sephadex, RP-18, polyamide, Toyopearl and XAD resin. Compounds effective for improving sexual dysfunction such as erectile dysfunction represented by Formula 1 and Formula 2 of the present invention can be isolated and purified. Column chromatography can be carried out several times by selecting an appropriate filler as necessary. In particular, column chromatography using Sephadex, RP-18 and silica gel as a filler is most preferably performed in combination.

Through the column chromatography process, it was possible to separate flavonoid compounds such as Cushenol H, Cushenol K, Curalinol, Sophoflavesenol, and Curaridine from ethyl acetate extract of Ginseng. The activity was the strongest. Therefore, the active ingredients that the ginseng extract of the present invention inhibits the activity of cGMP-PDE5 to play an important role in improving sexual dysfunction such as erectile dysfunction, Cushenol H, Cushenol K, Kurarinol, Sophoflavesinol, Kura It has been confirmed that these are flavonoid compounds such as ridine, which further demonstrates the results of the present invention that Ginseng extract is effective in improving sexual dysfunction such as erectile dysfunction.

Hereinafter, the present invention will be described in more detail based on Experimental Examples and Examples. However, these Examples are only for illustrating the present invention, and the technical scope of the present invention is not limited thereto.

Example 1 Preparation of Ginseng Extract

Finely chopped the roots of red ginseng, and dried 9.0 kg of dry ginseng in 20 L of methanol, extracted for 4-5 days at room temperature, and filtered. The methanol solution extracted three times was concentrated in a rotary concentrator at 40 ° C. to obtain a methanol extract. 257 g of methanol extract of red ginseng was suspended in 2000 ml of water, extracted with dichloromethane (CH ₂ Cl ₂ , 2000 ml × 3), and the aqueous layer was extracted with ethyl acetate (EtOAc, 2000 ml × 3). Again extracted well with butanol (BuOH, 2000 mL x 3). The resulting extract solution was filtered and concentrated to give each fraction.

Example 2 Separation and Purification Methods

14.08 g of ethyl acetate fraction of high ginseng was subjected to column chromatography (4 x 35 cm) using silica gel (230-400 mesh). The solvent used as the developing solvent was a mixed solvent of ethyl acetate-methanol-water (70: 5: 2) and gradually increased in polarity, and a mixed solvent of ethyl acetate-methanol-water (100: 10: 7) and ethyl acetate-methanol A mixed solvent of water (100: 13.5: 10) was used. The obtained fractions were observed by pure silica gel thin layer chromatography (developing solvent: ethyl acetate-methanol-water = 100: 13.5: 10), and then the compounds having similar polarities were collected and divided into eight small fractions (fractions 1 to 8). . Small fraction 2 (5.2 g) was subjected to Sepadex column chromatography (4.5 x 40 cm) using methanol as a developing solvent and column chromatography using silica gel (300 g) to obtain six small fractions (E2A to E2F). Got it. The solvent used was a mixed solvent of hexane-dichloromethane-methanol (10: 10: 2 → 5: 10: 3) and a mixed solvent of dichloromethane-methanol-water (50: 10: 1). Small fraction E2C (0.52 g) was subjected to column separation using Sephadex (MeOH, 2.5 × 36 cm) and recrystallized with methanol to obtain pure novel compound Sophoflavesenol (27 mg). Small fraction E2D (1.8 g) was subjected to reversed phase column chromatography (Cat.No .: 13900, Merck, 70% methanol, 3 x 30 cm) to give curarinol (530 mg), and small fraction E2E (1.1 g) ) Was purified using Sephadex, reversed phase column chromatography and MCI gel sequentially to obtain pure Cushenol K (180 mg) and Cushenol H (167 mg). In addition, small fraction E2B (0.47 g) was subjected to silica gel column chromatography using a dichloromethane-methanol-water (100: 13: 1) mixed solvent as a developing solvent and reverse phase column chromatography using 70% methanol. Lidine (24 mg) was obtained.

Experimental Example 1 cGMP-PDE5 Activity Inhibition Experiment

Inhibition experiment of cGMP-PDE5 activity of the ginseng extract and the components isolated therefrom was performed as follows.

cGMP-PDE5 was used separately from the diaphragm tissue of mice according to known methods (Lugnier C et al. , Biochem. Pharmacil. , 1986, 35, 1743-1751). The tissue was homogenized using a 5-fold volume of herpes buffer (20 mM HERPES, 0.25 M Sucrose, 1 mM PMSF, pH 7.2). This was filtered with two layers of surgical gauze and centrifuged at 100,000 rpm for 60 minutes at 4 ° C., the supernatant was filtered through a 0.2 μm filter paper, and 20 mM bis-Tris, 3 mM EDTA, Equilibrate the column with 50 mM sodium acetate buffer solution (pH 6.5) containing 0.2 mM DTT, 1 mM benzamide and 1 μM PMSF, then give PDE isozyme with concentration gradient with 1 M sodium acetate buffer (pH 6.5). (isozyme) eluted. For these fractions, the PDE5 fractions were separated by measuring the activity of PDE as described below, and the fractions were used to measure the degree of inhibition of cGMP-PDE5 activity of the test substance.

Into a tube, add 100 µl of the reaction solution (15 mM Tris-HCl, 5 mM MgCl ₂ , pH 7.4) to the PDE sample (20-40 µl), and mix well. Then, [3H] -GMP (22000 dpm / µl) The reaction was started by the addition of the test substance and reacted for about 20 minutes in a 30 ℃ thermostat. Thereafter, the reaction tube was immersed in boiling water for about 2 minutes to terminate the reaction. The tube was cooled in an ice bath for about 10 minutes, snake venom protein (5 μl as 10 mg / ml) with 5′-nucleotase activity was added, and then reacted in a 30 ° C. thermostat for about 10 minutes. , 0.5 ml of cooling water was added. The reaction solution was poured into a DEAE-Sephacel anion exchange resin column (0.5 × 50 mm), and the enzyme reaction product not bound to the ion resin was eluted with 2 ml of distilled water, and 10 ml of radioactivity cocktail (Ultima Gold) was added thereto. Enzyme activity was calculated by adding and measuring the radioactivity using the β-counter.

(1) Preparation of Ginseng Extract and Measurement of Inhibitory Effect of cGMP-PDE5 Activity

The ginseng extract obtained in Example 1 was measured for the inhibitory effect of cGMP-PDE5 activity using the above experimental method.

As a result, as shown in Table 1 , butanol fraction and water fraction of Ginseng showed a weak inhibitory effect on cGMP-PDE5 activity, whereas methanol, dichloromethane and ethyl acetate fractions had cGMP-PDE5 inhibitory activity, respectively. IC ₅₀ values of 4.77 μg / ml, 2.34 μg / ml and 1.54 μg / ml have been shown to be potent inhibitors of cGMP-PDE5 and have been found to be useful for improving sexual dysfunction such as erectile dysfunction, such as sildenafil.

Table 1 summarizes the cGMP-PDE5 activity inhibitory effect of each extract fraction obtained in Example 1.

Solvent fraction cGMP-PDE5 activity inhibitory activity (IC ₅₀ , ㎍ / mL) Methanol Extract of Ginseng 4.77 Dichloromethane Fraction from Ginseng 2.34 Ethyl acetate fraction of ginseng 1.54 Butanol fraction of ginseng 24.79 Water fraction of ginseng 24.50

(2) Determination of cGMP-PDE5 activity inhibitory effect of components isolated from Korean ginseng

For the flavonoid compounds obtained in Example 2, their cGMP-PDE5 activity inhibitory effect was measured using the above experimental method.

As a result, all five flavonoid compounds of the isolated compounds Cushenol H, Cushenol K, Curarinol, Sophoflavesenol and Curaridine inhibited cGMP-PDE5 activity in a concentration-dependent manner (see FIG. 1 ). Based on these results, the IC ₅₀ value that inhibits the 50% activity is shown in Table 2 , among which the most potent effect of inhibiting cGMP-PDE5 activity of vesofflavesenol. Analysis of PDE5 inhibitory mechanisms of curarinol, phosphoflavesenol, and curaridine with relatively high inhibitory effects among the active ingredients (see FIGS. 2 to 4 ) showed competitive or mixed activity inhibition.

Isolated components cGMP-PDE5 activity inhibitory activity (IC ₅₀ , ㎍ / mL) Cusholol H 4.75 Cusholol K 10.6 Curarinol 6.1 Sofoflavesenol 0.013 Curaridine 0.64

Therefore, Cushenol H, Cushenol K, Curalinol, Sophoflavesenol, Curaridine, or alcohol extracts of Ginseng, Dichloromethane extract of Ginseng, and ethyl acetate extract of Ginseng, according to the present invention, inhibit cGMP-PDE5 activity. It was found to be effective in improving sexual dysfunction such as erectile dysfunction due to its excellent effect.

Experimental Example 2 Acute Toxicity of Oral or Intraperitoneal Administration in Mice

In vivo acute toxicity test of flavonoid compounds such as Cushenol H, Cushenol K, Curarinol, Sophoflavesenol, Curaridine and extracts of the present invention among the substances represented by Formula 1 or Formula 2 are as follows. It was performed together.

Six mice (C57BL / 6 mice) per experimental group were used, and the compounds and extracts of the present invention were administered orally or intraperitoneally in each dose step at a dose of up to 10,000 mg / kg. The oral administration group was observed for 2 weeks, and the intraperitoneal administration group was observed for 1 week. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed, and hematological and blood biochemical tests were performed.

As a result, there were no clinical symptoms or deaths in all animals treated with the test substance, and no toxicity change was observed in weight change, blood test, blood biochemistry test, autopsy findings, etc.

From the above results, it can be seen that the compound and extract of the present invention have very high bio stability since the anti-lethal dose (LD ₅₀ ) does not show any toxic effect at 10,000 mg / kg or more upon oral administration or intraperitoneal injection in mice.

Preparation Example 1 Manufacturing Method of Syrup

Syrup containing the compound and the extract of the present invention as an active ingredient is prepared by the following method.

The compound, saccharin and sugar of the present invention were dissolved in 80 g of warm water. After the solution was cooled, a solution consisting of glycerin, saccharin, spices, ethanol, sorbic acid and distilled water was prepared and mixed thereto. Water was added to this mixture to 100 ml. The addition salt can be replaced with other salts according to the examples.

The components of the syrup are as follows.

Compound of the present invention (or ginseng extract of the present invention) 0.5 g

Saccharin: 0.8 g ··············

25.4 g of sugar

Glycerin ... 8.0 g

Spices ··················· 0.04 g

Ethanol 4.0 g

0.4 g of sorbic acid

Distilled water ·····················

Preparation Example 2 Preparation of Tablet

Tablets containing 0.5 g of active ingredient are prepared by the following method.

0.5 g of the compound of the present invention or ginseng extract was mixed with 17.6 g of lactose, 18 g of potato starch and 3.2 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 16 g of potato starch, 5.0 g of talc and 0.5 g of magnesium stearate was refined.

The components of the tablet are as follows.

Compound of the present invention (or ginseng extract of the present invention) 0.5 g

Lactose ························· 17.69 g

Potato starch 18 g

Colloidal silicic acid 3.2 g

10% gelatin solution

Potato Starch 16 g 16 g ················

Talc ····················· 5 g

0.5 g of magnesium stearate

Preparation Example 3 Manufacturing Method of Injection Solution

Injection solution containing 0.03 g of the active ingredient was prepared by the following method.

0.03 g of the compound of the present invention or Gosam extract, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. The solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.

The components of the injection solution are as follows.

Compound of the Invention (or Ginseng Extract of the Invention) 0.03 g

Sodium Chloride ... 0.6 g

Ascorbic acid ・ ・ ・ 0.1 g

Distilled water ······················

As described above, the compound represented by the formula (1) or the formula (2) of the present invention and the extract of ginseng comprising the same have excellent cGMP-PDE5 activity inhibitory effect and less toxicity, which is excellent in improving sexual dysfunction such as erectile dysfunction. Indicates.

Claims (5)

A composition for improving sexual dysfunction comprising a compound represented by the following Chemical Formula 1 or Chemical Formula 2, a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate compound thereof, an isomer thereof, or a mixture thereof as an active ingredient. Formula 1 (In the above formula, R ₁ is a C ₅ to C ₁₁ straight or crushed alkenyl group which is unsubstituted or substituted with a hydroxy group, R ₂ is hydrogen, hydroxy or C ₁ -C ₃ alkoxy, R ₃ and R ₄ are each independently hydrogen or hydroxy, Dotted lines indicate single bonds or double bonds.) Formula 2 The compound of claim 1 wherein said compound is (1) 2- (2,4-Dihydroxy-phenyl) -3,7-dihydroxy-8- [2- (3-hydroxy-3-methyl-butyl) -3-methyl-but-3 -Enyl] -5-methoxy-chroman-4-one (Cushenol H, Formula 3) Formula 3 (2) 2- (2,4-Dihydroxy-phenyl) -3,7-dihydroxy-8- [2- (3-hydroxy-3-methyl-butyl) -3-methyl-but-3 -Enyl] -5-methoxy-chroman-4-one (Kuschenol K, Formula 4) Formula 4 (3) 2- (2,4-dihydroxy-phenyl) -7-hydroxy-8- [2- (3-hydroxy-3-methyl-butyl) -3-methyl-but-3-enyl] -5-methoxy-chroman-4-one (curanol, formula 5) Formula 5 (4) 3,7-dihydroxy-2- (4-hydroxy-phenyl) -5-methoxy-8- (3-methyl-but-2-enyl) -chromen-4-one (vesoplast Besenol, formula 6) Formula 6 (5) 1- [2,4-Dihydroxy-3- (2-isopropenyl-5-methyl-4-hexenyl) -6-methoxy-phenyl] -3- (2,4-dihydro Roxy-phenyl) -propenone (curaridine, formula 7) Formula 7 Composition for improving sexual dysfunction, characterized in that. The sexual to the Sophora (Sophora flavescenes AITON) extract obtained contains a compound of claim 1 and, after extraction with a lower alcohol, a function (函數) alcohol, dichloromethane or ethyl acetate and the C ₁ ~C ₄ and evaporated under reduced pressure and filtration as an active ingredient Disorder improvement composition. Filtration and evaporation under reduced pressure comprising the compound of claim ₁ , obtained by extracting with C _{1 to} C ₄ lower alcohols, and then the solution suspended in water is extracted with dichloromethane, ethyl acetate or butanol and then filtered and A composition for improving sexual dysfunction, comprising a ginseng extract obtained by evaporation under reduced pressure as an active ingredient. Extracting ginseng with ethyl acetate, filtering and evaporating under reduced pressure to obtain ethyl ginseng acetate extract, the extract was prepared using a filler selected from the group consisting of silica gel, Sephadex, RP-18, polyamide, Toyopearl and XAD resin. Separation and purification method characterized by obtaining column compound by performing column chromatography.