CN113559159A - Composition for inhibiting type 5 phosphodiesterase activity - Google Patents
Composition for inhibiting type 5 phosphodiesterase activity Download PDFInfo
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- CN113559159A CN113559159A CN202110993090.9A CN202110993090A CN113559159A CN 113559159 A CN113559159 A CN 113559159A CN 202110993090 A CN202110993090 A CN 202110993090A CN 113559159 A CN113559159 A CN 113559159A
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Abstract
The object of the present invention is to provide a novel composition capable of inhibiting PDE5 activity. A composition for inhibiting type 5 phosphodiesterase activity comprises a processed product of at least 1 plant selected from the group consisting of genus Filipendula (Filipendula), genus Myrica (Myrica), genus Eugenia (Eugenia), genus Lagerstroemia (Lagerstroemia), genus Terminalia (Terminalia), genus Quercus (Haematoxylon) and genus Uncaria (Uncaria).
Description
(this application is a divisional application of application 201780081426.6 entitled "composition for inhibiting phosphodiesterase type 5 Activity", filed 12/22/2017)
Technical Field
The present invention relates to a composition for inhibiting type 5 phosphodiesterase activity.
Background
Phosphodiesterases (PDEs) are enzymes that hydrolyze cyclic gmp (cgmp), cyclic amp (camp), and there are many families in mammals.
Among them, phosphodiesterase type 5 (PDE5) is mainly involved in the decomposition of cGMP. cGMP functions as an intracellular second messenger, relaxing smooth muscle and increasing blood flow. Thus, by inhibiting PDE5 activity, smooth muscle can be relaxed and blood flow increased.
As a drug utilizing this effect, a PDE5 inhibitor is known, and a drug containing sildenafil citrate as an active ingredient is known as a typical drug. PDE5 inhibitors are used for the purpose of improving symptoms such as decreased erectile ability of the penis, decreased functions of the bladder and prostate, and pulmonary hypertension, because they inhibit the decomposition of cGMP by inhibiting PDE5 activity, thereby increasing local blood flow.
In addition, for example, it is known that zingiber officinale roscoe can inhibit PDE activity (patent document 1).
Documents of the prior art
Patent document
Patent document 1 Japanese patent laid-open publication No. 2013-224326
Disclosure of Invention
Problems to be solved by the invention
The object of the present invention is to provide a novel composition capable of inhibiting PDE5 activity.
Means for solving the problems
As a result of intensive studies on the above-mentioned problems, the present inventors have found that PDE5 activity can be inhibited by plants belonging to the genera Rubus (Rubus), Punica (Punica), comfrey (Filipendula), Myrica (Myrica), cherokee rose (Eugenia), Lagerstroemia (Lagerstroemia), Terminalia (Terminalia), sambucus (Haematoxylon), polygonum (Fallopia) or Uncaria (Uncaria).
The present invention has been completed based on this finding through further repeated studies, and is disclosed below.
A composition for inhibiting type 5 phosphodiesterase activity, comprising a processed product of at least 1 plant selected from the group consisting of Rubus (Rubus), Punica (Punica), Filipendula (Filipendula), Myrica (Myrica), Psidium (Eugenia), Lagerstroemia (Lagerstroemia), Terminalia (Terminalia), Geum (Haematoxylon), Polygonum (Fallopia) and Uncaria (Uncaria).
The composition of item 1, wherein the plant belonging to the genus Rubus is at least 1 selected from Himalayan blackberry (Rubus armeniacaus Focke), European blackberry (Rubus fructicosus), and North American raspberry (Rubus strigosus).
The composition of item 1, wherein the plant belonging to the genus Punica is Punica granatum (Punica grantum).
Item 4 the composition of item 1, wherein the plant belonging to the genus Filipendula is Filipendula ulmaria.
Item 5. the composition of item 1, wherein the plant belonging to the genus Myrica is at least 1 selected from the group consisting of Myrica rubra (Myrica ceraria) and Myrica rubra (Myrica rubra).
Item 6 the composition of item 1, wherein the plant belonging to the genus Caryophyllum is at least 1 selected from the group consisting of prunus communis (Eugenia uniflora) and caryophylli flos (Eugenia aromaticum).
The composition of item 7. the composition of item 1, wherein the plant belonging to the genus Lagerstroemia is Lagerstroemia speciosa (Lagerstroemia speciosa).
Item 8. the composition of item 1, wherein the plant belonging to the genus Terminalia is at least 1 selected from Terminalia catappa and Terminalia bellirica.
Item 9. the composition of item 1, wherein the plant belonging to the genus Logania is Logania japonica (Haematoxylon camphiciana).
Item 10 the composition of item 1, wherein the plant belonging to the genus polygonum is polygonum cuspidatum (Fallopia japonica).
The composition of item 1, wherein the plant belonging to the genus Uncaria is Uncaria guianensis (Uncaria guianensis).
The composition according to any one of items 1 to 11, which is used for prevention or improvement of at least 1 selected from the group consisting of penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy and pulmonary hypertension.
The composition according to any one of items 1 to 12, which is a food composition, a pharmaceutical composition or a feed composition.
Effects of the invention
According to the present invention, PDE5 activity can be inhibited. Therefore, the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by a decrease in blood flow accompanying cGMP decomposition, such as penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension.
Detailed Description
The present invention provides a composition for inhibiting type 5 phosphodiesterase activity, which comprises a processed product of at least 1 plant selected from the group consisting of Rubus (Rubus), Punica (Punica), Filipendula (Filipendula), Myrica (Myrica), Psidium (Eugenia), Lagerstroemia (Lagerstroemia), Terminalia (Terminalia), Picea (Haematoxylon), Polygonum (Fallopia) and Uncaria (Uncaria).
In the composition of the present invention, the raw material of the processed product of the above-mentioned plant contained as the active ingredient may be any one of plants belonging to the genera Rubus, Punica, Filipendula, Myrica, Prunus, Lagerstroemia, Terminalia, Picea, Polygonum and Uncaria.
Rubus genus belongs to Rosaceae family, and examples of the plant belonging to this genus include Himalayan blackberry (Rubus armeniacaus Focke), European blackberry (Rubus fructicosus), and North American raspberry (Rubus strigosus), but the present invention is not limited thereto.
The genus Punica belongs to the family of lythraceae, and examples of the plant belonging to the genus Punica include Punica granatum (Punica granatum) and the like, but the present invention is not limited thereto.
The genus Filipendula belongs to the family Rosaceae, and examples of the plant belonging to the genus Filipendula ulmaria include Filipendula ulmaria (Filipendula ulmaria), and the like, but the present invention is not limited thereto.
The genus Myrica belongs to the family Myricaceae, and examples of the plant belonging to the genus Myrica may include Myrica ceraria rubra (Myrica ceraria), Myrica rubra (Myrica rubra), and the like, but the present invention is not limited thereto.
The genus cherokee belongs to the family myrtaceae, and examples of plants belonging to this genus include prunus cerasus (Eugenia uniflora), clove (Eugenia aromaticum), and the like, but the present invention is not limited thereto.
Lagerstroemia indica (Lagerstroemia speciosa) belonging to the family lythraceae, and examples of the plant belonging to the genus Lagerstroemia speciosa (Lagerstroemia speciosa) may be mentioned, but the present invention is not limited thereto.
The genus Terminalia belongs to the family quisqualis, and examples of the plant belonging to this genus include Terminalia catappa (Terminalia cathpa), bellirica (Terminalia bellirica), and the like, but the present invention is not limited thereto.
The genus Locainia belongs to the family Leguminosae, and examples of plants belonging to this genus include Locairia (Haematoxylon camphiciana), but the present invention is not limited thereto.
Polygonum genus belongs to the family Polygonaceae, and examples of the plant belonging to this genus include Polygonum cuspidatum (Fallopia japonica), etc., but the present invention is not limited thereto.
The Uncaria genus belongs to the family rubiaceae, and examples of the plant belonging to the genus include Uncaria (Uncaria guianensis) and the like, but the present invention is not limited thereto.
These may be used alone in 1 kind, or may be used in combination of 2 or more kinds.
The plant to be used is not particularly limited as long as it is a plant, and examples thereof include leaves, stems, fruits, flowers, buds, branches, trunks, barks, roots, flower buds, seeds, and seed coats, and they may be appropriately selected according to the plant. Preferred examples include leaves, stems, fruits, bark, roots, stems, flower buds, etc., more preferred examples include leaves and fruits of Rubus, fruits of Punica, leaves and stems of Filipendula, barks of Myrica, fruits and flower buds of Psidium, leaves of Lagerstroemia, fruits of Terminalia, stems of Naja, stems and leaves of Polygonum, and roots, stems and leaves of Uncaria. The sites of use may be 1 type alone or 2 or more types in combination.
The processed product of the plant in the present invention includes a pulverized product, a dried product, an extract, and the like of the plant as the raw material.
The pulverized material is not particularly limited as long as the plant is pulverized by 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 plant, and can be obtained by a conventionally known drying method such as sun drying, far infrared ray irradiation, and a dryer (hot air drying, cold air drying, vacuum freeze drying). The amount of water in the dried product is preferably 10% by weight or less, and more preferably 8% by weight or less. The form of the dried product in the present invention is not limited, and any dried product of the plant body itself, pulverized dried product, or the like may be used. The dried pulverized product can be obtained by pulverizing the dried product in the same manner as the above pulverized product. In addition, as the dried product in the present invention, a dried product obtained by drying a plant as a raw material after fermentation treatment or enzyme treatment can be used.
The method for producing the extract (extraction method), extraction conditions, and the like are not particularly limited, and conventionally known methods may be used. For example, the plant may be subjected to crushing, drying, or the like as it is or if necessary, and then subjected to pressing or solvent extraction to obtain an extract. As the solvent extraction method, any known method in the art may be used, and for example, a conventionally known extraction method such as water (including warm water and hot water) extraction, alcohol extraction, supercritical extraction, or the like can be used.
When solvent extraction is performed, examples of the solvent include water; alcohols (anhydrous or aqueous) such as lower alcohols including methanol, ethanol and isopropanol, and polyhydric alcohols including propylene glycol and 1, 3-butylene glycol; ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile and ethyl acetate, xylene, benzene and chloroform. The solvent is preferably water, a lower alcohol, 1, 3-butanediol, etc., more preferably water, methanol, ethanol, 1, 3-butanediol, and even more preferably water, methanol, hydrous ethanol. These solvents may be used alone in 1 kind, or may be used in combination in 2 or more kinds.
In the present invention, an extract obtained by such solvent extraction can be particularly referred to as a solvent extract. As described above, for example, water may be used as the solvent to obtain a water extract, lower alcohols may be used to obtain a lower alcohol extract, and ethanol may be used to obtain an ethanol extract.
The obtained extract may be used as it is, or may be dried and used in the form of a solid such as powder or granule. The obtained extract may be subjected to purification, concentration, separation for separating a highly active fraction, and the like as required. The present invention is not limited thereto, and examples of the purification treatment include filtration, adsorption using an ion exchange resin or an activated carbon column, and decolorization. Further, as the concentration treatment, a conventional method such as an evaporator can be used. As the separation treatment for separating 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.
For example, the extract obtained as described above (further, a dried product, a purified product, a concentrated product, or a highly active fraction thereof) may be subjected to a freeze-drying treatment and powdered, and may be powdered by a conventionally known method such as a method of adding an excipient such as dextrin, corn starch, or gum arabic as necessary and powdering by a spray-drying treatment, or the like, to obtain the extract used in the present invention. The extract may be used by dissolving in water, ethanol, or the like as needed.
As the extract of the plant, it is preferable to exemplify an extract obtained by drying, pulverizing and/or cutting a plant (a site to be used) as a raw material, extracting with a preferable solvent, filtering, and further drying the extract thus obtained. The extract can be obtained by a method in which 100g of a plant as a raw material, more preferably 100g of a dried product, a pulverized product and/or a cut product of the plant, is immersed in 1 to 50 liters of an extraction solvent, extracted at an arbitrary temperature (for example, 15 to 90 ℃) for an arbitrary period of time (for example, 10 minutes to 24 hours) with stirring as necessary, and then filtered. The processed product of the plant of the present invention is preferably a plant extract (including dried products thereof).
The processed product of the plant used in the present invention may be a commercially available product, or a product obtained by further subjecting a commercially available product to a treatment such as drying.
The processed plant products thus obtained may be used alone in 1 kind, or in combination of 2 or more kinds.
The content of the processed product of the plant in the composition of the present invention is not limited as long as the effect of the present invention can be obtained, as long as the processed product of the plant is contained in the composition. In the composition, the processed product of the plant may be contained in an amount of more than 0% by weight, preferably more than 0% by weight and less than 100% by weight, more preferably 0.001 to 99% by weight, in terms of a dry matter. When 2 or more kinds of processed products are used, the total amount thereof satisfies the value. The dried processed product can be obtained by subjecting the processed product to a freeze-drying treatment. The freeze-drying process is carried out by vacuum concentration using a general evaporator. The more detailed processing sequence follows the later described embodiment.
In the composition of the present invention, the amount of the processed product of the plant to be administered (ingested) is not particularly limited as long as the effect of the present invention can be exhibited, and may be appropriately set in accordance with the physique, age, symptom, applicable form, purpose of use, degree of the expected effect, and the like of the subject (subject animal). The amount of the processed product of the plant to be administered (ingested) for 1 day is preferably 0.001 to 8000mg, more preferably 0.01 to 5000mg, in total (in terms of dry weight) based on an adult having a weight of 60kg, but the present invention is not limited thereto. The composition of the present invention may be administered (ingested) once or a plurality of times per day.
The compositions of the present invention may be administered orally or non-orally. The form of the composition of the present invention is not limited, and may be appropriately set according to the purpose. Examples of the form of the composition of the present invention include liquid forms such as liquid, emulsion, suspension, syrup, extract, spirit, elixir, and the like; semi-solid or solid state forms such as powder, granule, fine granule, tablet, pill, capsule (including hard capsule and soft capsule), buccal preparation, masticatory, gel, cream, paste, mousse, sheet, and liquid lyophilized extract; in addition, aerosol, patch, plaster, percutaneous absorption preparation, and other forms.
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, or the composition of the present invention may be in a sustained-release form. For example, the tablet may be a tablet coated with a conventionally known coating, for example, a sugar-coated tablet, a gelatin-coated tablet, an enteric-coated tablet, a film-coated tablet, a double-layer tablet or a multilayer tablet, as required.
The mode of use of the composition of the present invention is not limited, and may be appropriately set according to the purpose. The composition of the present invention can be used as a food composition (including a beverage, a health-care functional food (including a specific health-care food, a nutritional functional food, a health-care product, and the like), a food for patients), a pharmaceutical composition, a feed composition, or an additive for a food composition, a pharmaceutical composition, a feed, and the like.
The composition of the present invention may be produced by a conventional method known in the art, such as the above-described forms and modes of use, and may be produced by mixing any of pharmaceutically acceptable ingredients, cosmetically acceptable ingredients, and edible ingredients, as required. Examples of the optional component include a solvent (lower alcohol such as water, methanol, ethanol, or isopropyl alcohol; alcohol such as polyhydric alcohol such as propylene glycol or 1, 3-butylene glycol (either anhydrous or aqueous), or the like), a vehicle, a disintegrating agent, a diluent, a lubricant, a perfume, a coloring agent, a sweetening agent, a corrigent, a suspension, a wetting agent, an emulsifier, a solubilizer, a dispersant, a buffer, a binder, a penetration promoter, a stabilizer, a swelling agent, a preservative, a thickener, a pH adjuster, a surfactant, a coating agent, an absorption promoter, an adsorbent, a filler, an antioxidant, an anti-inflammatory agent, a refreshing agent, a film forming agent, a gelling agent, an amino acid, a vitamin, an enzyme, and various nutritional ingredients. These may be used alone in 1 kind, or may be used in combination of 2 or more kinds.
In the present invention, the subject (subject animal) of the composition is not limited, and examples thereof include humans and mammals other than humans. Examples of the non-human mammal include animals whose type 5 phosphodiesterase promotes cGMP degradation, and examples thereof include animals such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, pigs, cows, and horses, and preferably animals such as mice, rats, guinea pigs, rabbits, dogs, and monkeys.
The composition of the present invention can inhibit phosphodiesterase type 5 (PDE5) activity by using the processed product of the above plant as an active ingredient. Accordingly, the present invention provides a method for producing a composition for inhibiting PDE5 activity, characterized by using a processed product of the above-mentioned plant. The present invention also provides a method for producing a composition for inhibiting PDE5 activity, which comprises the step of preparing a processed product of the plant. The present invention also provides a method for inhibiting PDE5 activity, which comprises using the processed product of the above plant.
Thus PDE5 activity can be inhibited using the compositions of the invention. Thus, according to the present invention, it is possible to inhibit cGMP decomposition and to use the composition of the present invention for the purpose of preventing or ameliorating diseases caused by PDE5 activity or local blood flow reduction.
Therefore, the composition of the present invention is useful for preventing or improving penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy, pulmonary hypertension, and the like, but the present invention is not limited thereto. For example, relaxation of smooth muscle by PDE5 inhibition can increase blood flow in the corpus cavernosum penis, improve penile erection function, improve lower urinary tract disorders by increasing blood flow in the urinary system, relieve prostatic hypertrophy by increasing blood flow in the prostate and urethra, and reduce pulmonary arterial pressure by increasing blood flow in lung tissue.
Thus, the composition of the present invention can be suitably used also for a subject who intends to male functions, a subject who intends to urination functions, and the like.
The composition of the present invention can be used as a PDE5 activity inhibitor, a therapeutic agent for penile erectile dysfunction (insufficiency), a therapeutic agent for lower urinary tract dysfunction, a therapeutic agent for prostatic hypertrophy, a therapeutic agent for pulmonary hypertension (particularly pulmonary arterial pulmonary hypertension), and the like.
Examples
The present invention will be described in more detail below by way of examples, but the present invention is not limited to these examples.
Test example 1
1. Processed product of plant
Extracts of plants shown in table 1 were prepared using the plants as raw materials. Specifically, for examples 1, 5, 9 and 10, extracts were prepared according to the following procedure, and for the other examples, commercially available products were used.
Example 1: himalayan blackberry
50g of dried leaves of Himalayan blackberry were pulverized, 1000ml of water was added thereto, and extraction treatment was performed at 80 ℃ for 1 hour. The obtained extract was filtered using mirastroth (manufactured by MERCK MILLIPORE corporation), and the filtrate from which insoluble components were removed was lyophilized to obtain himalayan blackberry extract (7.9 g of extract dried substance).
Example 2: european blackberry
The extract of leaf of European blackberry (manufactured by Nippon Kagaku K.K., specially manufactured, dried powder) was used. The extract is obtained by pulverizing dried leaf of Rubus fruticosus, extracting with methanol, filtering, and lyophilizing the filtrate.
Example 3: north American red berry
The extract of leaves and fruits of Raspberry (specifically, powder dried product, manufactured by Nippon Kagaku Co., Ltd.) was used. The extract is obtained by pulverizing dried leaves and fruits of Rubus corchorifolius, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Example 4: pomegranate
An extract of pomegranate peel (product name pomegranate peel extract powder, product of Eiken, dried powder) is used.
Example 5: filipendula ulmaria (L.) Merr
40g of the dried material of the stem and leaf of Filipendula ulmaria was pulverized, 1000ml of water was added thereto, and extraction treatment was performed at 80 ℃ for 1 hour. The obtained extract was filtered using mirastroth (manufactured by MERCK MILLIPORE), and the filtrate from which insoluble components were removed was lyophilized to obtain Filipendula ulmaria extract (extract dry matter 9.9 g).
Example 6: waxberry
An extract of the bark of Myrica rubra (manufactured by Nippon Kagaku K.K., specifically, dried powder) was used. The extract is obtained by pulverizing dried bark of Myrica rubra, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Example 7: red bayberry
An extract of the bark of Myrica rubra (manufactured by Nippon Kagaku K.K., specifically, dried powder) was used. The extract is obtained by pulverizing dried bark of Myrica rubra, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Example 8: flat cherry
An extract of prunus flat fruit (manufactured by japan new chemicals co., ltd., special product, dried powder) was used. The extract is obtained by pulverizing dried fruits of prunus cerasus, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components are removed.
Example 9: clove
50g of dried bud of clove was pulverized, 1000ml of water was added thereto, and extraction treatment was performed at 80 ℃ for 1 hour. The obtained extract was filtered using MIRACLOTH (MERCK MILLIPORE), and the filtrate from which insoluble components were removed by lyophilization was used to obtain a clove extract (10.1 g of dry extract).
Example 10: lagerstroemia speciosa (bge.) hand. -Mazz
60g of dried leaves of Lagerstroemia speciosa are pulverized, 900ml of 50 mass% ethanol (water/ethanol mass ratio 1:1) is added, and extraction treatment is performed at 25 ℃ for 12 hours. The obtained extract was filtered using mirastroth (manufactured by MERCK MILLIPORE corporation), ethanol was distilled off from the filtrate from which the insoluble component was removed, and then lyophilized to obtain a banaba extract (8.9 g of extract dried product).
Example 11: terminalia catappa
An extract of the fruit of Terminalia catappa (manufactured by Nippon Kagaku K.K., specially-produced, dried powder) was used. The extract is obtained by pulverizing dried fruit of Terminalia catappa, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Example 12: buerger
An extract of fruit of Terminalia bellirica (manufactured by Nippon Kagaku K.K., specifically, dried powder) was used. The extract is obtained by pulverizing dried fruit of Terminalia bellirica, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Example 13: adopt wood
An extract of a tree trunk of a tree (manufactured by Nippon Kagaku K.K., specifically, a dried powder) was used. The extract is obtained by pulverizing dried trunk of harvested wood, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components are removed.
Example 14: giant knotweed rhizome
Extracts of stem and leaf of Polygonum cuspidatum (manufactured by Nippon Kagaku K.K., specially, dried powder) were used. The extract is obtained by pulverizing dried stem and leaf of rhizoma Polygoni Cuspidati, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Example 15: ramulus Uncariae cum uncis
Extracts of the root, stem and leaf of Uncaria guianensis (manufactured by Nippon Kagaku K.K., specially-produced, dried powder) were used. The extract is obtained by pulverizing dried root, stem and leaf of Uncaria guianensis, extracting with methanol, filtering the obtained extract, and lyophilizing the filtrate without insoluble components.
Comparative example: black ginger
Extract of black ginger rhizome (product name of black ginger extract-P, oil-processed product of Oryya, powder-dried product) is used. Hejiang is a plant currently known to have an inhibitory effect on Phosphodiesterase (PDE).
2.5 determination of Phosphodiesterase (PDE) inhibition Activity
The inhibitory activity of each extract prepared in the above 1 (n-3) on PDE5 was measured. In this Assay, PDE5A Assay Kit (#60350) (manufactured by BPS BIOSCIENCE Co., Ltd.), a 96-well plate, an automatic pipette, and a Perkinelmer EnVision2102 Multilabel Reader (manufactured by PERKINELMER) were used, and the inhibitory activity was measured in accordance with the instructions attached to the Kit.
Specifically, 25. mu.L of each well was added with diluted FAM-Cyclic-3 ', 5' -GMP. In each of the "controls" 25. mu.L of PDE buffer was added. Then, after adding an extract-containing solution obtained by mixing 600mg of the extract prepared as described above with 20mL of dimethyl sulfoxide, 5. mu.L of the extract-containing solution was mixed with 495. mu.L of sterilized water to prepare a sample solution (the extract concentration was 300. mu.g/mL). To each well was added 5 μ L of sample solution ("test" wells) or sample solvent ("blank control", "substrate control", "positive control" wells). Next, 20. mu.L of PDE assay buffer was added to each well of the "blank control" and "substrate control". Diluted prepared PDE5A was added to each well of the "test", "positive control" 20 μ L (200 pg/reaction well). The reaction was carried out at 25 ℃ for 1 hour. The diluted binder was added to each well in an amount of 100. mu.L, and reacted while vigorously shaking at 25 ℃ for 30 minutes. Fluorescence polarization was measured using a microplate reader (Excitation: 475-. The "blank" value was subtracted from each measurement value to calculate the fluorescence polarization value. In addition, the IC50 measurement was performed by reducing the concentration of the sample solution in stages to obtain the sample concentration at which the inhibition rate reached 50%.
3. Results
The results are shown in Table 1. IC50 values are shown in table 1.
[ Table 1]
As is clear from Table 1, the IC50 value (μ g/mL) of Heiguan ginger is greater than 50. On the other hand, the extracts of the plants shown in examples 1 to 15 all confirmed more excellent inhibitory activity of PDE5, and the inhibitory activity of these extracts of the plants was much higher than that of zingiber nigrum.
From this, it was confirmed that PDE5 activity can be inhibited more effectively by using a processed product of the plant than by using a plant, Zingiber zerumbet Smith, which is known to have an inhibitory effect on PDE activity.
Test example 2
1. Determining the order of operations
The amount of cyclic guanosine-phosphate (cGMP) in rat tissues was measured using the extracts of examples 1, 4, 5 and 10, the extract of comparative example, and water as a control, which were prepared in the above test examples.
SD male rats (weighing about 250 g/rat), cGMP ELISA kit (ADI-900-014, manufactured by Enzo Life Sciences), and Perkinelmer EnVision2102 Multilabel Reader (manufactured by Perkinelmer) were used for the measurement.
Specifically, 2g of the extract was mixed with 8mL of distilled water, and the solution containing the extract (500mg/2mL/kg body weight) was prepared immediately before each administration. The obtained administration solution was administered into the stomach of rats using a feeder (n-8) 0 hours and 24 hours after the start of the test. 25 hours after the start of the test, the penis of the rat was taken out under anesthesia and subjected to cryopreservation with liquid nitrogen. The amount of cGMP in penile tissue was determined by the method described in the cGMP ELISA kit. The amount of cGMP in the penile tissue was measured by intragastric administration in the same manner except that distilled water was used as a control instead of the administration solution containing the extract.
2. Results
The results are shown in Table 2.
[ Table 2]
As is clear from table 2, the cGMP amount when black ginger was administered was slightly higher than that when distilled water was administered. In contrast, the cGMP amount when the extracts of examples 1, 4, 5 and 10 were administered was about 2 times or more, or much more than 2 times, that when black ginger was administered.
Thus, the values obtained from the processed products of examples 1, 4, 5 and 10 were larger than those obtained from black ginger, and it was confirmed that diseases caused by the activity of PDE5 and the reduction of local blood flow could be more effectively prevented or improved by the processed products of examples 1, 4, 5 and 10.
Furthermore, as is clear from the results of test example 1, from the viewpoint of the inhibitory effect on PDE5 activity, the processed products of examples 2, 3, 6 to 9 and 11 to 15 are much higher than those of black ginger, and it was confirmed that the processed products of examples 2, 3, 6 to 9 and 11 to 15 are also more effective in preventing or ameliorating diseases caused by PDE5 activity and local blood flow reduction.
Claims (10)
1. A composition for inhibiting phosphodiesterase type 5 activity, comprising:
contains a processed product of at least 1 plant selected from the group consisting of genus Filipendula (Filipendula), genus Myrica (Myrica), genus Eugenia (Eugenia), genus Lagerstroemia (Lagerstroemia), genus Terminalia (Terminalia), genus Quercus (Haematoxylon) and genus Uncaria (Uncaria).
2. The composition of claim 1, wherein:
the plant belonging to the genus Filipendula is Filipendula ulmaria.
3. The composition of claim 1, wherein:
the plant belonging to the genus Myrica is at least 1 selected from the group consisting of Myrica rubra (Myrica ceraria) and Myrica rubra (Myrica rubra).
4. The composition of claim 1, wherein:
the plant belonging to the genus Caryophyllum is at least 1 selected from the group consisting of prunus communis (Eugenia uniflora) and caryophylli flos (Eugenia aromaticum).
5. The composition of claim 1, wherein:
the plant belonging to the genus Lagerstroemia is Lagerstroemia speciosa (Lagerstroemia speciosa).
6. The composition of claim 1, wherein:
the plant belonging to the genus Terminalia is selected from at least 1 of Terminalia catappa and Terminalia bellirica.
7. The composition of claim 1, wherein:
the plant belonging to the genus Logania is Logania japonica (Haematoxylon camphiciana).
8. The composition of claim 1, wherein:
the plant belonging to the genus Uncaria is Uncaria guianensis (Uncariaria guianensis).
9. The composition of any one of claims 1 to 8, wherein:
it is used for preventing or improving at least 1 selected from the group consisting of penile erectile function, lower urinary tract dysfunction, prostatic hypertrophy and pulmonary hypertension.
10. The composition of any one of claims 1 to 8, wherein:
it is a food composition, a pharmaceutical composition or a feed composition.
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| JP2016256466A JP7058939B2 (en) | 2016-12-28 | 2016-12-28 | Composition for inhibiting phosphodiesterase 5 activity |
| CN201780081426.6A CN110167571A (en) | 2016-12-28 | 2017-12-22 | Composition is used in the inhibition of 5 type phosphodiesterase activities |
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| US20220080021A1 (en) * | 2019-01-17 | 2022-03-17 | University-Industry Cooperation Group Of Kyung Hee University | Composition for preventing or treating prostatic hyperplasia comprising mixed extracts of curcumae radix and syzygii flos |
| JPWO2021106857A1 (en) * | 2019-11-29 | 2021-06-03 | ||
| WO2021106856A1 (en) * | 2019-11-29 | 2021-06-03 | 小林製薬株式会社 | Composition for improving urinary tract function and composition for improving blood flow in bladder |
| JP7368340B2 (en) * | 2020-11-13 | 2023-10-24 | 金氏高麗人参株式会社 | Composition for inhibiting phosphodiesterase 5 |
| FR3122990B1 (en) | 2021-05-20 | 2024-06-28 | Patrinove | Plant extract with crassulacean acid metabolism for use in the treatment of erectile dysfunction |
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| JP2003183122A (en) | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | Agent for inhibiting activity of collagenase |
| KR100462173B1 (en) * | 2004-06-08 | 2004-12-16 | 안국약품 주식회사 | A composition for prevention and treatment of urinary incontinence |
| ITMI20050068A1 (en) * | 2005-01-21 | 2005-04-22 | Ignazio Abbruzzo | PASTA DENTIFRICIA COMPOSED MAINLY BY A COMMON PLANT RUBUS FRUTICOSUS WHICH PARTS OF IT CONTAIN AN ACTIVE PRINCIPLE THAT FIGHTS THE DENTAL CARIES GIVES THE HEALTH OF THE GUMS AND THE CLEANING OF THE TEETH |
| KR20140101520A (en) | 2013-02-11 | 2014-08-20 | 주식회사한국전통의학연구소 | A pharmaceutical composition for improving generative of male and treating infertility |
| WO2014126269A1 (en) | 2013-02-12 | 2014-08-21 | 주식회사 한국전통의학연구소 | Pharmaceutical composition for improving male sexual function and for treating infertility |
| CN103520618B (en) * | 2013-10-21 | 2015-08-26 | 孟庆坤 | A kind of pharmaceutical composition for the treatment of erection disturbance and preparation method thereof and pharmaceutical applications |
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| JP2018108946A (en) | 2018-07-12 |
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