KR20050107387A - Erectile dysfunction treating agent comprising ogalpi extract - Google Patents

Abstract

The present invention relates to an erectile dysfunction therapeutic agent containing an alcoholic extract as an active ingredient, the organolpi alcohol extract of the present invention is excellent in the effect of increasing the erection of the penis can be usefully used to treat erectile dysfunction.

Description

Erectile dysfunction treating agent comprising Ogalpi extract}

The present invention relates to a therapeutic agent for erectile dysfunction containing an alcohol extract as an active ingredient.

Penile erection is a complex physiological reaction caused by the overall action of blood vessels, endocrine system, nervous system, etc. A relatively rigid white membrane as the cavernous smooth muscle is relaxed by various stimuli and the pores are expanded and the blood pressure increases due to the expansion of the small arteries. The subarachnoid veins in the small microcavity are pressed by the swelling of the pores, preventing the leakage of venous blood, which leads to increased penile pressure (Lue TF, Tanagho EA., J Urol , 1987, 137, 829). -36). As the physiological phenomenon of penile erection is revealed and the pharmacological action and mechanism of various drugs on cavernous smooth muscle are studied, efforts are being made to use drugs that have a relaxing effect on smooth muscle for the treatment of erectile dysfunction. Current substances that relax cavernous smooth muscle include adrenergic α receptor blockers, cholinergic drugs, NO (Nitric oxide), peptides, prostaglandins, histamines, calcium channel blockers, potassium channel openers, and nonspecific vasodilators (Linet OI). , Ogrinc FG., N Eng J Med , 1996, 334, 873-7; Tong YC et al ., Pharmacology , 1992, 45, 241-9; Miller MA et al ., Int J Impot Res, 1995, 7, 91 -100; Andersson KE, Wagner G., Physiol Rev , 1995, 75, 191-236; Andersson KE, Stief CG., World J Uro , 1997, l15, 14-20; Andersson KE., Pharmacol Rev , 2001, 53 , 417-50).

There is no accurate study of the frequency of erectile dysfunction, but the increase in average life expectancy, the increase in adult disease and diet, the increase of industrial accidents and traffic accidents due to industrial socialization, and the physical fatigue and mental stress caused by complex modern life Erectile dysfunction patients are on the rise. The treatment of erectile dysfunction includes medical treatment such as drug use, male hormone administration, surgical treatment such as vascular surgery, penile implant insertion, and intravascular penile catheter injection. In medical pharmacotherapy, male hormones, yohimbin, apomorphine, trazodone, etc. are generally used, except for severe organic erectile dysfunction. And low therapeutic effects and no reproducible drug (Andersson KE, Pharmacol Rev , 2001, 53, 417-50; Montorsi F et al ., BJU International , 2003, 91, 446-54; Vitezic D , Pelcic JM, Int J Clin Pharmacol Ther , 2002, 40 (9), 393-403), currently Sildenafil is used as the primary treatment for erectile dysfunction (Heaton JP, Dean J, Sleep DJ, Int J Impot Res , 2002, 14, 61-4).

On the other hand, Ogalpi is used as a medicinal herb in herbal medicine, has a hot taste, bitterness, warm properties, and is known to act on the liver, nerves, and nerves to get rid of customs and nourish the essence. In addition, it was used to show the auropathy (sickness caused by the weakness of the five intestines) and the seven statues (seven symptoms caused by the weakness of a man) and to use the legs poorly. It is known to help the body, to improve energy, to clear the mind, to increase the willpower, to prevent the body from becoming light and old, and to cure the bad blood inside the body cleanly and cleanly. It is known to cure various symptoms such as women's ulcers. Thus, Ogalpi has been used as a nourishing tonic for a long time in Korea, and has been used as some health food. Although Acanthopanax senticosus extracts have been reported to have hepatoprotective activity (Chun-Ching Lin and Pei-Chen Huang, Phytotherapy Research , 2000, 14, 489-494), studies on sexual function of organolpi have been reported. none.

Accordingly, the present inventors have confirmed that 70% ethanol extract or distilled water extract of each root and stem area for white hair gallop, thorn galgalpi, minagacio galpi, and island galpi, which are native to Korea, cause penile erection and develop erectile dysfunction symptoms. The present invention has been completed by revealing that it can be used as an improved health food and therapeutic agent.

It is an object of the present invention to provide an alcoholic extract of Ogalpi with erectile dysfunction symptoms.

It is also an object of the present invention to provide a health food for erectile dysfunction symptoms containing the alcohol extract as an active ingredient.

It is also an object of the present invention to provide an erectile dysfunction therapeutic agent containing the organgalpi alcohol extract as an active ingredient.

In order to achieve the above object, the present invention provides an organgalpi alcohol extract having an effect of improving erectile dysfunction.

In another aspect, the present invention provides a health food for erectile dysfunction symptoms containing the extract of the extract as an active ingredient.

The present invention also provides a therapeutic agent for erectile dysfunction containing the alcohol extract as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention provides an organopi alcohol extract having an effect of improving erectile dysfunction.

In the above, the organolpi is preferably selected from the group consisting of Acanthopanax divaricatus var.albeofructus, Acanthopanax senticosus, Acanthopanax senticosus var.subinermis, and Acanthopanax koreanum. It is more preferable that it is an organ. In addition, the extract of the organgalpi of the present invention is preferably the stem or root extract of the organ, and more preferably the stem extract of the organ. In the present invention, the stem refers to a part (ground part) except for the root.

In addition, the alcohol is preferably selected from the group consisting of methanol, ethanol, propanol and butanol, and more preferably ethanol. In addition, the alcohol is preferably 0 to 100% concentration, more preferably 70% concentration.

When the extracts of stems or roots of the hairy white hairs, white hairs, white hairs, or white hairs of the present invention are treated on rabbit corpus cavernosum smooth muscles, the degree of relaxation of the corpus cavernosum smooth muscles increases depending on the treated concentration. The organolpi extract has a strong relaxation effect on the corpus cavernosum smooth muscle, and has a better relaxation effect of the stem extract than the root extract (see FIG. 1a). In addition, the extract of the organolpi stem of the present invention is 70% ethanol extract compared to the distilled water extract This rabbit penile corpus cavernosum smooth muscle relaxation effect is better (see Fig. 1b). In addition, oral administration of 70% alcohol extract of the stem of the hairy Talpigal oral for a certain period of time to the rat increases the penile erection of the rat depending on the concentration and the duration of administration (see Figure 3). Therefore, the extract of Aggalpi improves the erectile power by relaxing the penile corpus cavernosum smooth muscle, and among them, 70% ethanol extract of the stem of the white hairy organolpi has the best effect.

NO (nitric oxide) is known to be involved in the relaxation of corpus cavernosum smooth muscle (Burnett AL, J Urol , 1997, 157, 320-4; Burnett AL et al ., Science , 1992, 257, 401-3). NO-producing substances bind to receptors on endothelial cell membranes to increase the concentration of free calcium in endothelial cells, which promotes NO synthesis and release. Free NO enters smooth muscle cells and activates guanylate cyclase of smooth muscle, resulting in increased production of cGMP. This increase in cGMP results in smooth muscle relaxation (Gonzalez-Cadavid NF, Ignarro LJ, Rajfer J, Mol Urol , 1999, 3, 51-9). There is no clear report on the relationship between NO and organolpi in corpus cavernosum smooth muscle. In a preferred embodiment of the present invention, the spongy smooth muscle relaxation effect of HS, which is the 70% ethanol extract of the white hairy gallbladder, which has the highest activity, removes the endothelial cells, or inhibits the action of acetylcholine, and atropine and ODQ, guanylate cyclase It was confirmed that it is affected by the administration of the inhibitor methylene blue, the NO inactivation pyrogallol, and the NO production inhibitor L-NNA (see FIG. 1C). Thus, the cavernous smooth muscle relaxation effect of HS is believed to be involved in endothelial cells and related to NO. On the other hand, it is observed that the concentration of cGMP in the corpus cavernosum smooth muscle is increased when HS relaxes the corpus cavernosum smooth muscle, and it can be seen that HS causes NO-related corpus cavernosum smooth muscle relaxation (see FIG. 2).

HS had no contraction or relaxation effect on stable cavernous smooth muscle, but it suppressed spontaneous movement in spontaneous movement. These spontaneous movements of smooth muscle are caused by direct smooth muscle, and most of them are not inhibited by neurologic drugs, but are lost by calcium or potassium related drugs and prostaglandin production inhibitors (Christ GJ et al ., Br J Pharmacol , 1990, 101, 375-81). Thus, as HS inhibits spontaneous movement, it can be seen that 70% ethanol extract of albino stems directly acts on cavernous smooth muscle.

Exposing the slice to the high potassium nutrient solution, which excludes calcium, virtually no storage capacity of smooth muscle is obtained. When calcium supplementation is performed, the storage capacity is restored by the inflow of calcium into the cell and contraction occurs. This action is known to occur mainly through a slowly activated membrane voltage-dependent calcium channel (Fovaeus M et al ., J Urol , 1987, 138, 1267-72; Karaki H et al ., Pharmacol Rev , 1997, 49, 157 -230). In a preferred embodiment of the present invention, the HS in the cavernous smooth muscle segment reached a stable state with little storage capacity in the calcium excreted high potassium nutrient solution, further reduced the basal tension of the cavernous smooth muscle (see Example <2-2>). This is due to the movement of calcium in the cytoplasm, and it is believed that the calcium in the cytoplasm was further leaked out or the calcium was introduced into the myoplasmic reticulum in the cytoplasm to further reduce the free calcium in the cytoplasm, thereby decreasing the storage capacity of the smooth muscle. HS also reduced concentration-dependent contractility of CaCl ₂ in calcium excreted high potassium nutrient solution. This inhibits the movement of calcium into the cell to some extent through the membrane voltage-dependent calcium channel in which the action of HS is slowly activated, leading to relaxation by reducing calcium in the cytoplasm.

In relaxation of penile cavernous smooth muscle, HS increased the intracavernosal concentrations of cGMP and cAMP in a concentration-dependent manner (see FIGS. 2 and 4). Therefore, it can be seen that the penile erection of HS is directly involved in cGMP-related penile corpus cavernosum relaxation as well as cAMP-related penile corpus cavernosum relaxation.

The present invention also provides a health food for erectile dysfunction symptoms containing the alcohol extract as an active ingredient.

The extract of the present invention has a strong relaxing effect on the rabbit penile corpus cavernosum smooth muscle, and when administered orally to the rat increases the penile erection of the rat depending on the concentration and duration of administration. Therefore, the composition of the present invention containing the organolpi extract as an active ingredient can be usefully used to improve the erectile dysfunction symptoms.

The organopi extract of the present invention can be added as it is to food or used together with other food or food ingredients, and can be suitably used according to conventional methods. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). In general, in the preparation of food or beverage, the agalpi extract of the present invention is added at 0.2 to 20% by weight, preferably 0.24 to 10% by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. Is sure.

There is no particular limitation on the kind of food. Examples of foods to which the substance can be added include drink, meat, sausage, bread, rice cake, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, drinks, Alcoholic beverages and vitamin complexes, and the like and include all healthy foods in the conventional sense.

The present invention also provides a therapeutic agent for erectile dysfunction containing the alcohol extract as an active ingredient.

The extract of the present invention has a strong relaxation effect on the rabbit penile corpus cavernosum smooth muscle, and can be useful for treating erectile dysfunction because oral administration to rats increases rat penile erection depending on the concentration and duration of administration.

In addition, 500 mg of the extract of the present invention was filled into capsules to prepare a galgal extract preparation, which was administered orally to 48 patients with erectile dysfunction for 2 months three times a day, two capsules per time, and then interviewed the patient. The questionnaire (improved sexual desire, improved erectile function, satisfaction, etc.) was used to investigate the effects of improving erectile dysfunction.

As a result, 35 out of 48 patients (72.9%) experienced improvement of foot function, and there were no side effects except two patients with indigestion. Therefore, the therapeutic agent containing the extract of the present invention as an active ingredient may be usefully used to treat erectile dysfunction by improving it.

Agalpi extract of the present invention may comprise 1 to 100 parts by weight based on the total weight of the erectile dysfunction therapeutic agent, preferably 50 to 100 parts by weight, in addition to one or more pharmaceutically acceptable carriers It can be prepared as. The carrier may include, but is not limited to, saline, buffered saline, water, glycerol and ethanol, and any suitable agent known in the art (Remingtons's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA) may be used. .

Ogalpi extract of the present invention can be administered orally at the time of clinical administration and can be used in the form of a general pharmaceutical formulation, when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used or Formulated using excipients.

The formulation of the present invention may be applied differently depending on the age, sex, condition, absorption of the active ingredient, inactivation rate and excretion rate of the subject, and the drug used in combination, for example, orally administered 1 to 1.5 g per day. It is not limited to this. The invention also includes formulations of dosage units. The formulations are present in individual dosage forms, such as tablets, coated tablets, capsules, pills, suppositories, and ampoules, wherein the amount of active compound in the drug corresponds to the fraction or multiple of the individual dosage. Dosage units may contain, for example, one, two, three or four times the individual dosage, or 1/2, 1/3 or 1/4 times. The individual dosages preferably contain an amount in which the active compound is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dosage.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and liquid preparations for oral use include suspensions, solvents, emulsions, and syrups. In addition to liquids and paraffins, various excipients may be included, such as wetting sweeteners, fragrances, preservatives and the like.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example 1 Preparation of Ogalpi Extract

Acanthopanax divaricatus var.albeofructus, Acanthopanax senticosus var.subinermis, and Acanthopanax koreanum used in this experiment were collected from Cheonan receiving product farms, and Acanthopanax senticosus was used. It was taken from Cheongoksan. Ogalpi was divided into roots and stems, dried, and then chopped. The extracts were prepared according to the Food and Drug Standard using 70% ethanol or distilled water. The extract used in the experiment was marked with white hairy galgalpi, H for thorny galgalpi, K for mingaciogalpi, and S for scorpiogalpi according to the type of used galgol, and stems (S, above ground except for roots). In combination with the root (R), 70% ethanol extracts of the four organgalpi were expressed as HR, HS, KR, KS, MR, MS, SR, SS, respectively. Samples extracted with distilled water were expressed as HSW, KSW, MSW, SSW.

Example 2 Relaxation Effect of Ogalpi Extract on Rabbit Penile Cavernous Smooth Muscle (In Vitro Experiment)

<2-1> Preparation of Rabbit Penile Cavernous Smooth Muscle Sections

The subjects were 85 male and female New Zealand White rabbits (Samtako BIO KOREA, Osan, Gyeonggi-do, Korea) who were 4-6 months old with similar structures and physiological erections. Sodium pentobarbital was anesthetized through rabbit bile veins at 30-50 mg / kg, and the penis was excised to provide a low temperature Tyrode solution (a mixture of 95% oxygen and 5% carbon dioxide). ^{composition: (mEq / L) Na +} 153.6, K + 5.3, Ca 2+ 3.0, Mg 2+ 1.2, Cl - 157.2, H 2 PO 4 - 0.6, SO 4 - 1.2, HCO 3 - 7.1 and glucose 5.0) Cavernous smooth muscle was isolated within. Sections of 2 × 2 × 6 mm were made from isolated cavernous smooth muscles and fixed in a 10 ml tissue bath containing a thyroid solution and connected to an isotropic systems (Biopac systems, Santa barbara, CA, USA). Motion of the cavernous smooth muscle was recorded. The thyroid solution in the tissue container was maintained at 37 ° C., and the oxygen mixture gas was continuously supplied at pH 7.4. Endothelial cell ablation experiments rubbed cavernous smooth muscle to remove endothelial cells (Kim N et al ., J Clin Invest , 1991, 88, 238-42). The cavernous smooth muscle fragments thus prepared were phenylephrine (5 x 10 ^-6 M). (Hereinafter abbreviated as "PHE") induced contraction and confirmed the presence of endothelial cells with or without acetylcholine (Ach) relaxation. After endothelial cell removal, only those specimens with no acetylcholine relaxation or acetylcholine relaxation within 10% prior to de-endothelial manipulation were selected and used as smooth muscle sections from which endothelial cells were removed. Experiments involving no endothelial cell removal used cavernous smooth muscle sections that had already been formed.

<2-2> Determination of the ideal tension for isotonic contraction

The initial tension was maintained at about 2 g and maintained to reach a stable state, and then the degree of contraction was observed by administration of PHE. After that, the endothelial cell sections were washed with thyroid solution to recover to a stable state, and the tension was increased or decreased to observe the degree of contraction by the same concentration of PHE at a stable state. When the time was set as the ideal tension and the drug reaction experiment was started in this ideal tension stable state.

<2-3> Effect of Ogalpi Extract on Strain of Cavernous Smooth Muscle

Spongy smooth muscle that reached a stable state was treated with PHE 5 x 10 ^-6 M concentration to induce contraction, and then the organolpi extract prepared in Example 1 was 1 mg / ml, 2 mg / ml, 5 mg / ml or At a concentration of 10 mg / ml, the exercise state of the cavernous smooth muscle was recorded in the same manner as in Example <2-1>.

As a result, first, the effect according to the extraction site of golgalpi (H), thorny golgalpi (H), thorny golgalpi (K), mingashigalpi (M), island golpi (S) of the stem (S) and root (R) of 70% respectively Ethanol-extracted samples HR, HS, KR, KS, MR, MS, SR and SS each showed a relaxation effect on rabbit cavernous smooth muscle in a concentration-dependent manner from 1 mg / ml. And, the degree of relaxation compared to S and R, except for M, S was stronger than R, and in the order of H, K, M, S, the effects were stronger. It was the strongest (Figure 1a). Therefore, it was found that the activity of the stem portion is the best.

Next, the effect according to the sample extracted from the highly active stem portion, among the four samples (HS, KS, MS, SS) extracted with 70% ethanol and four samples (HSW, KSW, MSW, SSW) extracted with distilled water 70% ethanol extract was more relaxed than distilled water extract. And, the relaxation effect of the HS of the extract was the strongest (Fig. 1b).

<2-4> Analysis of Cavernous Smooth Muscle Relaxation Mechanism of Ogalpi Extract

In order to investigate the relationship between NO and the relaxation activity of organolpi after contracting corpus cavernosum smooth muscle sections with PHE, 3 1H- [1,2, a guanylate cyclase-specific inhibitor, was applied to cavernous smooth muscle sections contracted with PHE. , 4] -oxadiazolo [4,3-α] quinoxaline-1-one (3 1H- [1,2,4] -oxadiazolo [4,3-α] quinoxalin-1-one, hereinafter "ODQ" la name card) to 10 ^-4 M, the cycle rate of nine not raise non-specific inhibitor methylene blue 10 ^-4 M, NO deactivated by oxygen free radical generator agent pyrogallol (pyrogallol) 10 ^-4 M or NO production inhibitor N ^W - Nitro-L-arginine (N ^W -nitro-L-arginine, hereinafter abbreviated as "L-NNA") was treated at 3 x 10 ^-4 M concentrations, respectively, and then the organopi extract HS was 1 mg / ml, 2 mg /. The degree of relaxation was measured by treatment at a concentration of ml, 5 mg / ml or 10 mg / ml.

In addition, to investigate the relationship with cholinergic neurotransmitters, atropine was treated at a concentration of 5 × 10 ⁻⁶ M, and the organgalpi extract HS was treated with 1 mg / ml, 2 mg / ml, 5 mg / ml or 10 mg /. The degree of relaxation was measured by treating with a concentration of ml.

In addition, in order to examine the relationship with endothelial cells in the relaxation of organolpi, the corpus cavernosum smooth muscle from which endothelial cells were removed was contracted with PHE, and the organolpi extract HS was 1 mg / ml, 2 mg / ml, 5 mg / ml or 10 mg. The degree of relaxation was measured by treatment at a concentration of / ml.

As a result, HS showed a concentration-dependent relaxation from the concentration of 1 mg / ml in the sections contracted by PHE, and the degree of relaxation was 27.6 ± 8.20%, 2 mg / ml, and 5 mg / ml at 1 mg / ml. And 45.2 ± 16.37%, 69.3 ± 12.57% and 97.8 ± 6.93% at 10 mg / ml, respectively. In addition, the relaxation effect of HS in corpus cavernosum smooth muscle sections was significantly affected by the removal of endothelial cells and by ODQ, methylene blue pretreatment, pyrogallol, atropine, and L-NNA (p <0.05) ( 1c).

In addition, to determine whether the relaxation activity of organgalpi is related to calcium, penile cavernous smooth muscle sections were washed with calcium-extracted high potassium depolarized solution to supplement CaCl ₂ 10 ^-3 M when the tension of cavernous smooth muscles fell to equilibrium. Shrinkage of corpus cavernosum smooth muscle was observed, and the organolpi extract was pretreated at a concentration of 1 mg / ml, 2 mg / ml, 5 mg / ml or 10 mg / ml, and then supplemented with CaCl ₂ 10 ^-3 M to compare the contraction. Observed.

As a result, when CaCl ₂ 10 ^-3 M was administered to calcium-exposed high potassium depolarized solution, the tension was 2.12 ± 1.21 g, but the concentration of HS was 1 mg / ml, 2 mg / ml, 5 mg / ml and 10 mg / ml. Treatment with CaCl ₂ reduced the shrinkage by CaCl ₂ to 62.85 ± 11.58%, 43.00 ± 7.60%, 24.44 ± 6.80% and 12.5 ± 5.42%, respectively (p <0.05).

Example 3 Effect of Ogalpi Extract on CGMP and cAMP Concentration in Rabbit Penile Cavernous Smooth Muscle (In Vitro Experiment)

Induced relaxation by administering organ galpi in PHE contraction of smooth corpus cavernosum smooth muscle, and immediately frozen tissues under maximum relaxation and stored at -70 ° C, followed by cGMP and cAMP kits (BIOTRA cellular communication assays kit) CGMP and cAMP were measured using an enzyme immunoassay (EIA) using Amersham pharmcia biotech, Buckinghamshire UK.

As a result, the concentrations of cGMP and cAMP in corpus cavernosum smooth muscle increased depending on the treatment concentration of Agalpi extract HS in corpus cavernosum smooth muscle sections contracted by PHE (FIG. 2).

All experimental results of Examples 1 to 4 were obtained from the average and standard error in the computer's accelerator program, and the significance of each measurement group was Mann-Whitney U test or Student's tee test. (student's t test), the smooth muscle tension change according to the drug concentration was determined to be a significant result when the p <0.05 using a simple regression test (simple regression test).

< Example  4> Effect of Ogalpi Extract on the Penile Erection in Rats ( In vivo  Experiment)

<4-1> Preparation of Ogalpi Extract

In the present invention, Acanthopanax divaricatus var. Albeofructus was collected from Cheonan Receiving Farm, and the stems were dried and then chopped, and 70% ethanol was used to prepare the extract (HS).

<4-2> Changes of Penile Cavernous Pressure Following Oral Administration of Ogalpi Extract in Rats

250-350 g of Sprague Dawley species male rats were studied. The rats were divided into the control group and the organalpi group, and the organal group was administered 50, 100, or 200 mg / kg of saline solution in physiological saline once a day directly to the oral cavity using a syringe. The administration period was 2 or 4 weeks. Was carried out.

Anesthesia was injected with 30-50 mg / kg of sodium pentobarbital in the abdominal cavity of the rat. The median incision was made to expose the bladder and prostate, and the main pelvic ganglion located in the posterior wall of the prostate was found. Was peeled off. Platinum electrodes were installed on the corpus cavernosum nerves and connected to an electrical stimulator (STM100A, Biopac system, Santa barbara, CA, U.S.A.). After the incision of the penile epidermis to expose the corpus cavernosum, 26G needles were placed in the corpus cavernosum for the measurement of intracavernosal pressure. The needle was attracted and the blood pressure was continuously measured through a transducer and a polygraph system. Systemic blood pressure and cavernosal pressure are connected to differential amplifiers (DA100, Biopac system, USA) via Sorenson transpac (Abbott Critical Care System, USA), and data acquisition (MP 100, Biopac). system, USA) and analyzed using a data analysis program (Acqknowledge 3.2 program, Biopac system, USA).

In addition, in order to evaluate the response of penile erection due to cavernous nerve stimulation, the cavernous pressure was measured according to cavernous nerve stimulation (frequency: 2Hz, threshold: 2 Volt), and the maximum cavernous pressure was compared.

As a result, oral administration of HS significantly improved penile erection compared to the control group (p <0.05). There was a difference in penile erection according to the dose and duration of HS. The erection was temporarily increased when administered at a concentration of 50 mg / kg / day for 2 weeks, but at a concentration of 100 mg / kg / day 4 Erection was best when administered for weeks. In addition, as the duration of administration increased, erection increased (FIG. 3).

< Example  5> Rat Penile Cavernous Body of Ogalpi Extract Smooth muscle cGMP  And cAMP  Effect on concentration (in vivo experiments)

After maximal penile erection was induced by neurostimulation of rat penile corpus cavernosum smooth muscles, tissues were immediately frozen and removed, and stored at -70 ° C and then cGMP and cAMP BIOTRA cellular communication assays kit ( Enzyme immunoassay (EIA) was performed using Amersham pharmcia biotech, Buckinghamshire UK to measure cGMP and cAMP.

As a result, it was confirmed that the concentration of cGMP and cAMP of the corpus cavernosum increased during penis erection in the control group that stimulated the corpus cavernosum smooth muscle in rats. In addition, after oral administration of HS 100 mg / kg / day for 2 or 4 weeks, the concentrations of cGMP and cAMP during penile erection by cavernous nerve stimulation were significantly increased (p <0.05) ( 4). Therefore, when oral administration of the extract was found that the concentration of cGMP and cAMP of the corpus cavernosum smooth muscle increases with long-term administration.

All the experimental results of Examples 1 to 6 were obtained by the average and standard error in the accelerator program of the computer, the significance of each measurement group was Mann-Whitney U test or Student Tee test (student's t test), the smooth muscle tension change according to the drug concentration was determined to be a significant result when the p <0.05 using a simple regression test (simple regression test).

Preparation Example 1 Preparation of Health Food Containing Ogalpi Extract

As described above, the extract of the present invention is excellent in improving the erectile dysfunction symptoms. Thus, the present inventors prepared a health food containing the organgalpi extract as an active ingredient as follows.

<1-1> Drink Production

522 mg of honey

Chioctosanamide 5 mg

Nicotinamide 10 mg

Riboflavin Sodium Hydrochloride 3 mg

Pyridoxine hydrochloride 2 mg

Inositol 30 mg

Orthoic acid 50 mg

Ogalpi Extract 1.28 mg

200 ml of water

With the above composition and content, drinks were prepared using conventional methods.

<1-2> Preparation of Chewing Gum

Gum base 20%

Sugar 76.36-76.76%

Ogalpi Extract 0.24-0.64%

1% fruit flavor

Water 2%

Chewing gum was prepared using conventional methods using the above composition and content.

<1-3> Preparation of Candy

50 to 60% sugar

Starch syrup 39.26-49.66%

Ogalpi Extract 0.24-0.64%

Orange flavor 0.1%

Candy was prepared using conventional methods with the above composition and content.

<1-4> Preparation of Biscuits

Force Class 1 88 kg

Gravity First Class 76.4 ㎏

16.5 kg per white

2.5 kg of salt

2.7 kg of glucose

Palm shortening 40.5 kg

5.3 kg of ammo

Medium kg 0.6 kg

0.55 kg sodium bisulfite

Rice flour 5.0 kg

Vitamin B1 0.003 kg

0.003 kg of vitamin B2

Milk Flavor 0.16 ㎏

71.1 kg of water

Whole milk powder 4 kg

Substitute powder 1 kg

0.1 kg of calcium phosphate

Spray salt 1 kg

25 kg of spray oil

Ogalpi Extract 0.2-0.5 kg

Biscuits were prepared using conventional methods with the above composition and content.

<1-5> Preparation of Ice Cream

Milkfat 10.0%

Non-fat solids 10.8%

Sugar 12.0%

Starch syrup 3.0%

Emulsifying stabilizer (span) 0.5%

Spices (Strawberries) 0.15%

Water 63.31-62.91%

Ogalpi Extract 0.24-0.64%

Ice cream was prepared using conventional methods using the above composition and content.

<1-6> Preparation of Chocolate

Sugar 34.36-34.76%

Cocoa Butter 34%

Cocoa Mass 15%

Cocoa Powder 15%

Lecithin 0.5%

0.5% vanilla

Ogalpi Extract 0.24-0.64%

With the above composition and content, chocolate was prepared using conventional methods.

<1-7> Preparation of noodles and ramen

By using the composition and content of the following Table 1 , using a fast and robust kneading machine, 2 kg of the mixture and 1.2 kg of the dough solution were mixed and stirred for 10 to 15 minutes to complete the composition. The finished composition is extruded in the form of noodle yarn with an extruder, and when noodle is molded by an extruder, steamed steam is removed by removing the first steam and dried using a freeze freeze dryer to prepare dried noodles. Natural drying does not shape properly and is not broken or hard boiled, but freeze-drying not only keeps the shape intact and boils well, but also softens the noodles and preserves the original ingredients.

Ramen noodles have the same molding process as dried noodles, and only the mold of the compression molding machine is different. Ramen noodles are packaged by frying in cooking oil after molding, or by freezing and drying immediately after steaming.

Furtherance content mixture Rice flour 40 wt% Wheat protein 30 wt% flour 15 wt% Starch 10 wt% Seomoktae Powder 5 wt% Dough solution water 90 wt% Ogalpi Extract 10 wt%

<1-8> Preparation of rice cake

2 kg of the mixture and 1 kg of dough solution were mixed as the composition and content of the following Table 2 , followed by stirring for 10 to 15 minutes to complete the composition by steaming. The finished composition is put into a slice or rice cake mold machine and extruded to make a rice cake.

Furtherance content mixture Rice flour 60 wt% Wheat protein 30 wt% Seomok Tae Flour 7 wt% Sugar 2 wt% Dough solution water 90 wt% Ogalpi Extract 10 wt% Refined salt a very small amount

<1-9> manufacturing of bread

Below with the composition and content of Table 3, to complete the mixture and the kneading liquid 2 ㎏ 900 g for 20 minutes the mixture composition by fermentation 30 minutes after stirring 35 ℃ ~ 40 ℃. Form this into a regular shape and steam it in a cauldron.

Furtherance content mixture Rice flour 30 wt% Wheat protein 30 wt% flour 30 wt% Seomok Tae Flour 8 wt% Duck sugar 2 wt% Dough solution water 90 wt% Ogalpi Extract 10 wt% Refined salt, powder, yeast a very small amount

Preparation Example 2 Preparation of an Erectile Dysfunction Therapeutic Agent Containing Ogalpi Extract as an Active Ingredient

The present inventors lyophilized the ethanol extract of the white hairy organulpi stem, which was proved to have the best effect of reducing erectile dysfunction in vitro and animal experiments of the above example, and made a powder to prepare an erectile dysfunction treatment by filling 500 mg per capsule. It was.

< Example  6> Clinical trial using Orgigapi extract for treatment of erectile dysfunction

Clinical trials were performed in patients with erectile dysfunction using the erectile dysfunction treatment agent prepared in Preparation Example 2. Forty-eight patients were enrolled. The mean age of the patients was 43.4 years, the oldest age was 50 years and the youngest age was 36 years. The method of administration was administered orally for 3 months, 2 capsules per time for 2 months. The subjects were 10 diabetic patients, 6 hypertensive patients, 4 hyperlipidemic patients, 12 psychogenic (psychiatric) erectile dysfunctions, 6 low testosterone patients, and 10 unexplained erectile dysfunction patients. Changes in erectile dysfunction were determined by a questionnaire survey that included items such as interviews with patients, sexual desire, improved erectile function, and satisfaction every two weeks for two months.

As a result, 35 out of 48 patients, 72.9% of patients, improved the function of the foot during two months of oral administration. There were no side effects other than two patients with indigestion. Therefore, it can be seen that the erectile dysfunction treatment agent containing the extract of the present invention as an active ingredient has a natural side effect as well as less side effects, and also has an excellent effect on reducing erectile dysfunction symptoms.

As described above, since the organolpi stem ethanol extract of the present invention has an excellent ability to increase the erection of the penis, it can be usefully used as a health food or erectile dysfunction treatment for erectile dysfunction symptoms.

1A is a graph comparing rabbit penile corpus cavernosum smooth muscle relaxation degree using 70% ethanol extract of stem or root of albino, thorny golpi, mingaciogalpi and island golpi.

1b is a graph comparing rabbit penile corpus cavernosum smooth muscle relaxation degree using the extract extracted from the stems of white hairs, psorigogalpi, mingaciogalpi and island ogalpi with distilled water or 70% alcohol.

Figure 1c is a graph showing the effect of the removal of endothelial cells, ODQ, methylene blue, pyrogallol, atropine or L-NNA on rabbit penile corpus cavernosum smooth muscle relaxation action of Aggalpi stem 70% ethanol extract (HS).

1A to 1C,

KS: 70% ethanol extract of Prunus stem,

HS: 70% ethanol extract of the white hairy stem

SS: 70% ethanol extract of Stalk

MS: 70% ethanol extract of the stem of Mingasiogalpi,

KR: 70% ethanol extract of the roots

HR: 70% ethanol extract of the white hair roots,

SR: 70% ethanol extract of island roots,

MR: 70% ethanol extract of the roots of Mingasiogalpi,

Figure 2 is a graph showing the concentration of cGMP and cAMP in rabbit penile corpus cavernosum smooth muscle according to the treatment concentration of Aggalpi stem 70% ethanol extract (HS).

Figure 3 is a graph comparing the degree of erection of the rat penis by administration concentration when oral administration of 70% ethanol extract (HS) of the hairy stems of the hairy Talpigol in 2 and 4 weeks in the rat.

FIG. 4 is a graph showing cGMP and cAMP concentrations of the corpus cavernosum smooth muscle muscles according to the administration period when oral administration of 70% ethanol extract (HS) of the white hairy stem of the hairy stem at 100 mg / kg for 2 or 4 weeks in rats. .

Claims (4)

Erectile Dysfunction Therapeutic agent comprising an extract of white hair Orgalpi alcohol or isogalpi as an active ingredient. The agent for treating erectile dysfunction according to claim 1, which is an extract of stem or root of organulpi. The agent for treating erectile dysfunction according to claim 1, wherein the alcohol is selected from the group consisting of methanol, ethanol, propanol and butanol. The agent for treating erectile dysfunction according to claim 3, wherein the alcohol is ethanol.