JP7367112B2 - Composition for inhibiting phosphodiesterase 5 activity - Google Patents

Description

The present invention relates to a composition for inhibiting phosphodiesterase-5 activity.

Phosphodiesterase (PDE) is a cyclic GMP (cG
It is an enzyme that hydrolyzes MP) and cyclic AMP (cAMP), and there are multiple families in mammals.

Among these, phosphodiesterase 5 (PDE5) is mainly involved in cGMP degradation. cGMP acts as an intracellular second messenger, relaxing smooth muscle and increasing blood flow. Therefore, by suppressing the activity of PDE5, smooth muscles are relaxed and blood flow is increased.

Today, PDE5 inhibitors are known as drugs that utilize this effect, and a typical example is a drug containing sildenafil citrate as an active ingredient. PDE5 inhibitors inhibit PDE5 activity, inhibit cGMP degradation, and increase local blood flow, with the aim of improving symptoms such as decreased penile erectile ability, decreased bladder and prostate function, and pulmonary hypertension. It is used as.

Furthermore, it is known that, for example, black ginger can inhibit the activity of PDE (Patent Document 1).

JP2013-224326A

The present invention aims to provide a new composition that can inhibit the activity of PDE5.

The present inventors have conducted extensive research in view of the above-mentioned problems, and have discovered the following plants: Rubus, Pomegranate, Filipendula, Myrica, and Eugenia. ), Lagerstroemia, Terminalia, Haematoxylon, Fallopia or Uncaria were found to be able to inhibit the activity of PDE5.
The present invention was completed as a result of further studies based on this knowledge, and is as follows.
Item 1. Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Terminalia, Haematoxylon, Myrica A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of (Fallopia) and Uncaria.
Item 2. Item 2. The composition according to item 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberry (Rubus armeniacus Focke), Rubus fruticosus, and American strawberry (Rubus strigosus). .
Item 3. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pomegranate is Pomegranate (Punica granatum).
Item 4. A plant belonging to the genus Filipendula ulmaria is Filipendula ulmaria.
Item 2. The composition according to item 1.
Item 5. Item 2. The composition according to item 1, wherein the plant belonging to the genus Myrica is at least one selected from the group consisting of Myrica cerifera and Myrica rubura. Item 6. 2. The composition according to item 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Eugenia uniflora and Eugenia aromaticum.
Section 7. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Crape Myrtle is Banaba (Lagerstroemia speciosa).
Section 8. Item 2. The composition according to item 1, wherein the plant belonging to the genus Terminalia is at least one selected from the group consisting of Terminalia catappa and Terminalia bellirica.
Item 9. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Haematoxylon campechianum is Haematoxylon campechianum.
Item 10. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Freckles is Japanese knotweed (Fallopia japonica).
Item 11. Item 2. The composition according to item 1, wherein the plant belonging to the genus Uncaria guianensis is cat's claw (Uncaria guianensis).
Item 12. Item 12. The composition according to any one of Items 1 to 11, which is used to prevent or improve at least one selected from the group consisting of penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension.
Item 13. Item 13. The composition according to any one of Items 1 to 12, which is a food composition, a pharmaceutical composition, or a feed composition.

According to the present invention, the activity of PDE5 can be inhibited. Therefore, the composition of the present invention can be used for the purpose of preventing or improving diseases caused by decreased blood flow due to cGMP degradation, such as penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. can do.

The present invention relates to Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Terminalia, Haematoxylon. ), Fallopia, and Uncaria.

As raw materials for the processed products of the plants contained as active ingredients in the composition of the present invention, Rubus genus, Pomegranate genus, Meadowsweet genus, Proteus genus, Eugenia genus, Crape Myrtle genus, Momotamana genus, Redwood genus, Freckle genus, and staghorn spp. Examples include plants belonging to any of the genera.

The Rubus genus belongs to the Rosaceae family, and examples of plants belonging to this genus include Himalayan blackberry (Rubus armeniacus Focke), Rubus fruticosus, and American strawberry (Rubus strigosus), although the present invention is not limited thereto. be done.

The genus Pomegranate belongs to the family Lythraceae, and examples of plants belonging to this genus include Pomegranate (Punica granatum), although the present invention is not limited thereto.

The genus Meadowsweet belongs to the Rosaceae family, and examples of plants belonging to this genus include Filipendula ulmaria, although the present invention is not limited thereto.

The genus Myrica belongs to the family Proteaceae, and examples of plants belonging to this genus include Myrica cerifera and Myrica rubura, although the present invention is not limited thereto.

The genus Eugenia belongs to the family Myrtaceae, and examples of plants belonging to this genus include Eugenia uniflora and Eugenia aromaticum, although the present invention is not limited thereto.

The genus Crape Myrtle belongs to the family Lythraceae, and examples of plants belonging to this genus include Lagerstroemia speciosa, although the present invention is not limited thereto.

The genus Momotamana belongs to the family Chrysanthemum, and examples of plants belonging to this genus include Terminalia catappa and Terminalia bellirica, although the present invention is not limited thereto.

The genus Haematoxylon belongs to the Fabaceae family, and examples of plants belonging to this genus include Haematoxylon campechianum, although the present invention is not limited thereto.

The genus Freckles belongs to the Polygonaceae family, and examples of plants belonging to this genus include Fallopia japonica, although the present invention is not limited thereto.

The genus Ceramus belongs to the Rubiaceae family, and examples of plants belonging to this genus include Cat's Claw (Uncaria guianensis), although the present invention is not limited thereto.

These may be used alone or in combination of two or more.

For these plants, the parts to be used are not particularly limited, but examples include leaves, stems, fruits, flowers, buds, branches, trunks, bark, roots, flower buds, seeds, seed coats, etc., and should be selected appropriately according to each plant. Bye. Preferably, leaves, stems, fruits, bark, roots, stems, flower buds, etc. are exemplified, and more preferably leaves and fruits of the genus Rubus, fruits of the genus Pomegranate, leaves and stems of the genus Meadows, bark of the genus Proteus, and bark of the genus Eugenia. Examples include fruits and flower buds, leaves for the genus Crape Myrtle, fruits for the genus Momotamana, stems for the genus Redwood, stems and leaves for the genus Freckles, and roots, stems, and leaves for the genus Crape. One type may be used alone, or two or more types may be used in combination.

In the present invention, the processed plant products include crushed products, dried products, extracts, etc. of the plants used as the raw materials.

The pulverized product is not particularly limited as long as it is obtained by pulverizing the plant using a pulverizer known in the art such as a jet mill.

The dried product is not particularly limited as long as it is obtained by drying the above-mentioned plants, and can be obtained by conventionally known drying methods such as sun drying, far-infrared irradiation, drying (hot air drying, cold air drying, vacuum freeze drying, etc.). be able to. Further, the moisture content in the dried product is preferably 10% by weight or less, more preferably 8% by weight or less. In the present invention, the form of the dried product is not limited, and may be either a dried product of the plant itself or a crushed product of the dried product. The dry pulverized product can be obtained by pulverizing the dried product according to the same method as for the above-mentioned pulverized product. In addition, in the present invention, as the dried product, it is also possible to use a product obtained by fermenting or enzymatically treating a raw material plant and then drying it.

The extract manufacturing method (extraction method) and extraction conditions are not particularly limited, and conventionally known methods may be followed. For example, after cutting, crushing, or drying the plant as it is, if necessary, the extract can be obtained by exploitation or solvent extraction. As the solvent extraction method, any method known in the art may be used, and for example, conventionally known extraction methods such as water (including hot water and hot water) extraction, alcohol extraction, and supercritical extraction can be used. .

When performing solvent extraction, examples of solvents include water; alcohols such as lower alcohols such as methanol, ethanol, and isopropanol, and polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (regardless of whether they are anhydrous or water-containing); ); Examples include ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile, and acetic acid ethyl ester, xylene, benzene, and chloroform. Preferred solvents are water, lower alcohols, 1,3-butylene glycol, etc., more preferred are water, methanol, ethanol, and 1,3-butylene glycol, and even more preferred are water, methanol, and aqueous ethanol. These solvents may be used alone or in combination of two or more.

In the present invention, the extract obtained through solvent extraction in this manner can be particularly referred to as a solvent extract. Further, although not limiting the present invention, as mentioned above, for example, when water is used as a solvent, a water extract, when a lower alcohol is used, a lower alcohol extract, and when ethanol is used, an ethanol extract is obtained. It can be called a thing.

The obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granules. Further, the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fractions, etc., as necessary. Although not limiting the present invention, purification treatments include filtration, adsorption using an ion exchange resin, activated carbon column, etc., and decolorization. Further, as the concentration treatment, a conventional method such as an evaporator can be used. Further, as a separation treatment for the highly active fraction, known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, and HPLC (High performance liquid chromatography) can be used.

In addition, for example, a method of subjecting the extract obtained as described above (and its dried product, purified product, concentrated product, and highly active fraction) to powder by freeze-drying, as necessary. The extract used in the present invention may be prepared by adding excipients such as dextrin, corn starch, and gum arabic, and pulverizing the mixture according to a conventionally known method such as spray drying. Further, the extract may be used after being dissolved in water, ethanol, etc., if necessary.

Preferably, the extract of the plant is an extract obtained by drying, crushing and/or cutting the raw material plant (part to be used), extracting it using a suitable solvent, and filtering it. An example is an extract obtained by further drying the obtained extract. The present invention is not limited to the present invention, and a person skilled in the art may extract the extract as appropriate depending on each plant or the part to be used. However, the extract is preferably a dried or crushed product per 100 g of the plant as a raw material. And/or the cut material is immersed in 1 to 50 liters of extraction solvent per 100 g, and is heated at any temperature (for example, 15 to 90°C) for any time (for example, 10 minutes to 24 hours) while stirring as necessary. ) can be obtained by extraction and subsequent filtration. In the present invention, the processed plant product is preferably a plant extract (including its dried product, etc.).

The processed plant product used in the present invention may be a commercially available product, or may be a commercially available product further subjected to appropriate treatments such as drying.

The processed plant products thus obtained may be used alone or in combination of two or more.

The content of the processed product of the plant in the composition of the present invention is not limited as long as the processed product of the plant is contained in the composition and the effects of the present invention can be obtained. It is exemplified that the processed product of the plant is contained in the composition in an amount of more than 0% by weight, preferably more than 0% by weight and less than 100% by weight, more preferably, in terms of dry matter. is 0.001 to 99% by weight. When using two or more types of processed products, the total amount satisfies the value. A dried product of the processed product can be obtained by freeze-drying the processed product. The freeze-drying process is performed by vacuum concentration using a general evaporator and freeze-drying in a vacuum state. More detailed processing procedures follow the examples described later.

In addition, in the composition of the present invention, the amount of the processed plant product to be administered (ingested) is not particularly limited as long as the effects of the present invention are achieved, and the amount is not particularly limited depending on the physique, age, symptoms, and application of the subject (target animal). It may be set as appropriate depending on the form, purpose of use, degree of expected effect, etc. Although not limiting the present invention, the total amount of the processed product of the plant (in terms of dry weight) is preferably 0.001 to 8000 mg per day, based on an adult with a body weight of 60 kg. A more preferred example is 0.01 to 5000 mg. The composition of the present invention may be administered (ingested) once or multiple times per day.

The composition of the present invention may be administered orally or parenterally. The form of the composition of the present invention is not limited either, and may be appropriately set depending on the purpose. The composition of the present invention may be in a liquid form such as a solution, emulsion, suspension, syrup, extract, spirit, elixir, powder, granule, fine granule, tablet, pill, capsule ( (including hard capsules and soft capsules), semi-solid or solid forms such as troches, chewables, gels, creams, pastes, mousses, sheets, and liquid freeze-dried products, as well as aerosols, patches, etc. Examples include various forms such as poultices and transdermal absorption preparations.

Further, for example, when the composition of the present invention is in a solid form, it may be used by mixing with water or the like, and the composition of the present invention may be in a sustained release dosage form. Furthermore, if necessary, the tablets may be coated with conventionally known coatings, such as sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, or multilayer tablets. .

Furthermore, the manner in which the composition of the present invention is used is not limited, and may be appropriately set depending on the purpose. Examples of uses of the composition of the present invention include food compositions (including beverages, foods with health claims (including foods for specified health uses, foods with nutritional function claims, foods with functional claims, supplements, etc.), and foods for patients); It can be used as an additive to pharmaceutical compositions, feed compositions, food compositions, pharmaceutical compositions, feeds, and the like.

The composition of the present invention may be manufactured according to conventionally known normal procedures in the various forms and usage modes described above, and, if necessary, pharmaceutically acceptable ingredients and cosmetic and cosmetically acceptable ingredients. It may be manufactured by mixing with any component such as edible components. Such optional components include solvents (water, lower alcohols such as methanol, ethanol, isopropanol, alcohols (whether anhydrous or water-containing) such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol, etc.) , excipients, disintegrants, diluents, lubricants, fragrances, colorants, sweeteners, corrigents, suspending agents, wetting agents, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers agent, stabilizer, filler, preservative, thickener, pH adjuster, surfactant, coating agent, absorption enhancer, adsorbent, filler, antioxidant, anti-inflammatory agent, cooling agent, film forming agent , gelling agents, amino acids, vitamins, enzymes, various nutritional ingredients, etc. These may be used alone or in combination of two or more.

In the present invention, the subjects (target animals) of the composition are not limited, but include humans and non-human mammals. Examples of mammals other than humans include animals in which phosphodiesterase 5 promotes the degradation of cGMP, such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, pigs, cows, and horses, preferably mice. Examples include animals such as , rats, guinea pigs, rabbits, dogs, and monkeys.

According to the composition of the present invention, the activity of phosphodiesterase 5 (PDE5) can be inhibited using the processed product of the plant as an active ingredient. From this, it can be said that the present invention provides a method for producing a composition for inhibiting PDE5 activity, which is characterized by using a processed product of the plant. Moreover, it can be said that the present invention provides a method for producing a composition for inhibiting PDE5 activity, which includes the step of preparing a processed product of the plant. Furthermore, the present invention can be said to provide a method for inhibiting PDE5 activity, which is characterized by using a processed product of the plant.

As described above, the composition of the present invention can inhibit PDE5 activity. Therefore, according to the present invention, cGMP degradation can be suppressed, and the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by PDE5 activity or decreased local blood flow.

Therefore, the composition of the present invention is useful for preventing or improving penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, pulmonary hypertension, etc., although the present invention is not limited thereto. For example, PDE5 inhibition relaxes smooth muscles, which increases blood flow to the corpus cavernosum, improving penile erectile function, and increasing blood flow to the urinary system, which improves the lower urinary tract. It can improve tract disorders, alleviate prostatic hypertrophy by increasing blood flow to the prostate and urethra, and reduce pulmonary artery pressure by increasing blood flow to the lung tissue. can.

For this reason, the composition of the present invention can also be preferably applied to subjects concerned about male function, subjects concerned about urinary function, and the like.

In addition, the composition of the present invention can be used as a PDE5 activity inhibitor, a drug for treating penile erectile function (dysfunction), a drug for treating lower urinary tract dysfunction, a drug for treating prostatic hyperplasia, a drug for treating pulmonary hypertension (particularly pulmonary arterial hypertension), etc. Can also be used as

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Test example 1
1. Processed Plant Products Using the plants shown in Table 1 as raw materials, extracts of each plant were prepared. Specifically, extracts were prepared according to the following procedure for Examples 1, 5, 9, and 10, and commercially available products were used for the other Examples.

Example 1: Himalayan Blackberry 50 g of dried Himalayan blackberry leaves was crushed, 1000 ml of water was added, and extraction was performed at 80° C. for 1 hour. The obtained extract was filtered using Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a Himalayan blackberry extract (7.9 g of dried extract).

Example 2: Yabu Strawberry A leaf extract of Yabu Strawberry (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract is obtained by crushing the dried leaves of St. japonica, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. be.

Example 3: American strawberry American strawberry leaf and fruit extracts (custom made by Nippon Shinyaku Co., Ltd., dried powder) were used. This extract is obtained by crushing the dried leaves and fruits of American strawberries, adding methanol to extract them, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. It is.

Example 4: Pomegranate Pomegranate peel extract (trade name: Pomegranate peel extract powder, manufactured by Koei Kogyo, dried powder) was used.

Example 5: 40g of dried stems and leaves of Natsuyukisou were crushed, 1000ml of water was added, and the mixture was heated at 80℃ for 1 hour.
The extraction process was carried out in hours. The obtained extract was filtered using Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a N. nightfall extract (9.9 g of dried extract).

Example 6: An extract of the bark of a white yam berry (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract is obtained by crushing the dried bark of the white yam, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. .

Example 7: Bayberry bayberry bark extract (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract was obtained by crushing dried bayberry bark, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.

Example 8: An extract of the fruit of Tachibana adek (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract is obtained by crushing the dried fruit of Tachibanaadeku, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. .

Example 9: Cloves 50 g of dried clove buds were crushed, 1000 ml of water was added, and extraction was performed at 80° C. for 1 hour. The obtained extract was filtered using Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a clove extract (10.1 g of dried extract).

Example 10: 60 g of dried Banaba banaba leaves were crushed, 900 ml of 50% by mass ethanol (mass ratio of water and ethanol 1:1) was added, and extraction treatment was carried out at 25° C. for 12 hours. The obtained extract was filtered using Miracloth (manufactured by Merck Millipore), ethanol was distilled off from the filtrate to remove insoluble components, and the banaba extract (8.9 g of dried extract) was obtained by freeze-drying. Obtained.

Example 11: Momotamana Momotamana fruit extract (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract was obtained by crushing the dry fruit of Momotamana, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.

Example 12: Seita camyobalan An extract of Seita camyobalan fruit (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract is obtained by crushing the dried fruit of Seita camillobalan, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. be.

Example 13: An extract of the trunk of Akuminokia (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract was obtained by crushing the dried trunk of red oak tree, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.

Example 14: Japanese knotweed An extract of stems and leaves of Japanese knotweed (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract is obtained by crushing the dried stems and leaves of Japanese knotweed, extracting it by adding methanol, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. be.

Example 15: Cat's Claw Cat's claw root, stem, and leaf extract (custom made by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract is obtained by crushing the dried roots, stems, and leaves of cat's claw, extracting by adding methanol, filtering the obtained extract, and freeze-drying the filtrate after removing insoluble components. It is something that

Comparative example: Black ginger An extract of the rhizome of Black ginger (trade name: Black ginger extract-P, manufactured by Oryza Yuka, dried powder) was used. Black ginger is a plant that has been known to have an inhibitory effect on phosphodiesterase (PDE).

2. Measurement of phosphodiesterase (PDE) 5 inhibitory activity 1. The inhibitory activity against PDE5 of each extract prepared was measured (n=3). In this measurement, PDE5A Assay Kit (#60350) (manufactured by BPS Biosciences), 96-well plate, Pipetman, PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer)
The inhibitory activity was measured according to the instructions provided with the kit.

Specifically, 25 μL of diluted FAM-Cyclic-3', 5'-GMP was added to each well. 25 μL of PDE buffer was added to “Blank”. Next, 600 mg of the extract prepared as described above and 20 mL of dimethyl sulfoxide were mixed to obtain an extract-containing solution, and then 5 μL of the extract-containing solution and 495 μL of sterile water were mixed to obtain a sample solution (extract concentration 300 μg). /mL). 5 μL of sample solution (“Test” well) or sample solvent (“Blank”, “Substrate control”, “Positive control” well) was added to each well. Next, 20 μL of PDE assay buffer was added to the “Blank” and “Substrate control” wells. 20 μL of the diluted PDE5A was added to the “Test” and “Positive control” wells (200 pg/reaction well). The reaction was carried out at 25°C for 1 hour. 100 μL of the diluted binding agent was added to each well, and reacted at 25° C. with vigorous shaking for 30 minutes. Fluorescence polarization was measured using a plate reader (Excitation: 475-495 nm, Emission: 518-538 nm). The "Blank" value was subtracted from each measurement value to calculate the fluorescence polarization value. Furthermore, for IC50 measurement, the concentration of the sample solution was decreased stepwise to determine the sample concentration at which the inhibition rate was 50%.

3. Results The results are shown in Table 1. Table 1 shows IC50 values.

As is clear from Table 1, the IC50 value (μg/mL) of black ginger exceeded 50. On the other hand, all of the plant extracts shown in Examples 1 to 15 exhibited superior PDE5 activity inhibitory effects, which greatly exceeded the inhibitory effects of black ginger.

This suggests that the processed product of the plant can inhibit PDE5 activity more effectively than black ginger, which is a plant that has been known to have an activity-inhibiting effect on PDE. was confirmed.

Test example 2
1. Measurement procedure Measure the amount of cyclic guanosine monophosphate (cGMP) in rat tissue using the extracts of Examples 1, 4, 5 and 10 prepared in the above test examples, the extract of the comparative example, and water as a control. did.

For this measurement, SD male rats (body weight approximately 250 g/animal), cGMP ELISA kit (ADI-900-014, manufactured by Enzo Life Sciences), and PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) were used.

Specifically, 2 g of the extract and 8 mL of distilled water were mixed to prepare the extract-containing administration solution (500 mg/2 mL/kg body weight) immediately before each administration. The obtained administration solution was administered into the stomach of rats using a probe at 0 hours and 24 hours after the start of the test (n=8). Twenty-five hours after the start of the test, the rat's penis was removed under anesthesia and cryopreserved using liquid nitrogen. The amount of cGMP in penile tissue was measured according to the method described in the cGMP ELISA kit. As a control, the administration was performed intragastrically in the same manner except that distilled water was used instead of the extract-containing administration solution, and the amount of cGMP in the penile tissue was measured.

2. Results The results are shown in Table 2.

As is clear from Table 2, the amount of cGMP upon administration of black ginger was slightly higher than the amount of cGMP upon administration of distilled water. On the other hand, the cGMP levels when administering the extracts of Examples 1, 4, 5, and 10 were about twice or much more than double when administering black ginger.

Thus, the values obtained for the processed products of Examples 1, 4, 5, and 10 exceeded the values obtained for black ginger, so according to the processed products of Examples 1, 4, 5, and 10, It was confirmed that diseases caused by PDE5 activity and decreased local blood flow can be more effectively prevented or improved.

Furthermore, as is clear from the results of Test Example 1, the processed products of Examples 2, 3, 6 to 9, and 11 to 15 greatly exceed black ginger in terms of PDE5 activity inhibition effect. Therefore, it was confirmed that the processed products of Examples 2, 3, 6 to 9, and 11 to 15 can also more effectively prevent or improve diseases caused by PDE5 activity and decreased local blood flow.

Claims (3)

Contains a solvent extract of the roots, stems and leaves of cat's claw (Uncaria guianensis) ,
The solvent is at least one selected from the group consisting of water, methanol, ethanol, isopropanol, propylene glycol, and 1,3-butylene glycol.
Composition for inhibiting phosphodiesterase 5 activity
(However, this excludes compositions containing butterflies, cuckoos, wampi, fennels, cacti, sandalwood, cornelian and cornelian) . The composition according to claim 1 , which is used for preventing or improving at least one selected from the group consisting of penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. Claim 1 or 2, wherein the composition is a food composition, a pharmaceutical composition, or a feed composition for preventing or improving at least one type selected from the group consisting of penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. 2. The composition according to 2 .