JP2011037829A - Smooth muscle relaxant - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a smooth muscle relaxant useful for circulatory disorders due to the hindrance of blood flow, blood pressure elevation, dysuria due to prostatomegaly, pollakiuria due to bladder contraction, and the like, and to provide a method for efficiently producing the smooth muscle relaxant. <P>SOLUTION: There are provided a smooth muscle relaxant containing isosamidin as an active ingredient; a food or drink containing the smooth muscle relaxant; a method for producing the smooth muscle relaxant; and a method for producing isosamidin which is an active ingredient for the smooth muscle relaxant. The smooth muscle relaxant is useful for improving vascular functions and for preventing and treating diseases caused by the contraction of smooth muscles. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a smooth muscle relaxant containing isosamidine as an active ingredient, a method for producing the smooth muscle relaxant, and a method for producing isosamidine.

  In recent years, so-called lifestyle-related diseases such as arteriosclerosis, hyperlipidemia, hypertension, and diabetes have rapidly increased with changes in dietary habits of high cholesterol and high calories and an increase in the age group due to the increase in life expectancy. It has become a big social problem.

  Hypertension is almost always lacking in subjective symptoms and progresses unknowingly to other organs and can cause various complications. The main complications include angina pectoris, myocardial infarction, cerebral infarction, decreased renal function, dissecting aortic aneurysm and the like. Recently, it has been reported that sleep apnea syndrome is also associated with a high rate. Some complications are severe and fatal to progress.

  Examples of a method for treating hypertension include vasodilation with a smooth muscle relaxant. Smooth muscles are involuntary muscles that form walls of blood vessels, prostate, bladder, urethra, digestive organs, uterus, bronchi and the like, and are deeply involved in the function of each tissue. As relaxing agents having a smooth muscle relaxing action, chlorzoxazone, papaverine hydrochloride and the like are known. In addition to hypertension, smooth muscle relaxants are used for the prevention and treatment of diseases caused by smooth muscle contraction, such as dysuria, frequent urination, and premature labor.

  On the other hand, the button bow (scientific name Peucedanum japonicum) is a perennial that belongs to the genus Pseudoaceae, also called long-lived grass or sacna. It grows on rocky shores and grasslands on the coast, has a stem of 30 to 100 cm, and has a flowering period of 6 to 9 When it comes to the moon, it attaches many small white flowers. In Okinawa, the place of origin, it is said that its physiological activity is effective for colds, fatigue recovery, and nourishing tonic, and it has been useful for a long time. In a recent study, it has been reported that the extract of button worms has a function of suppressing foaming of macrophages, which is an early lesion of arteriosclerosis (Patent Document 1).

International Publication No. 2006/08274 Pamphlet

  An object of the present invention is to provide a smooth muscle relaxant useful for circulatory disturbance due to stagnation of blood flow, an increase in blood pressure, dysuria due to prostatic hypertrophy, frequent urination due to bladder contraction, and the like. Is to provide a simple manufacturing method.

  To summarize the present invention, the first invention of the present invention relates to a smooth muscle relaxant containing isosamidine as an active ingredient. Examples of the smooth muscle relaxant of the first invention of the present invention include those containing a hydrous alcoholic extract or an anhydrous alcoholic extract derived from button bowfish containing isosamidine. In addition, examples of the smooth muscle relaxant of the first invention include a vasodilator, a bladder smooth muscle relaxant, and a prostate smooth muscle relaxant.

  The second invention of the present invention relates to a food or beverage containing the smooth muscle relaxant of the first invention of the present invention.

  The third invention of the present invention includes (1) a step of washing button fountain with water, and (2) a step of extracting isosamidine from the button fountain washed in step (1) using hydrous alcohol or anhydrous alcohol as an extraction solvent. A method for producing a smooth muscle relaxant of the first invention of the present invention. The alcohol concentration of the hydrous alcohol in the third invention of the present invention is exemplified by 40% by volume to 80% by volume, and the hydrous alcohol is exemplified by hydrous ethanol.

  According to a fourth aspect of the present invention, (1) a step of washing button fountain with water, and (2) a step of extracting isosamidine from the button fountain washed in step (1) using hydrous alcohol or anhydrous alcohol as an extraction solvent. It is related with the manufacturing method of isosamidine.

  The present invention provides a smooth muscle relaxant containing isosamidine as an active ingredient, an efficient method for producing the smooth muscle relaxant, and an efficient process for producing isosamidine which is an active ingredient of the smooth muscle relaxant. . The smooth muscle relaxant of the present invention is useful for improving vascular function and preventing or treating diseases caused by smooth muscle contraction.

It is a figure which shows the smooth muscle relaxation effect | action of isosamidine. It is a figure which shows the bladder contraction inhibitory effect of isosamidine. It is a figure which shows the prostate contraction inhibitory effect of isosamidine.

[1] Smooth muscle relaxant of the present invention The smooth muscle relaxant of the present invention contains isosamidine as an active ingredient. The inventors of the present invention have found that isosamidine contained in buttonfish has a smooth muscle relaxing action. This revealed that isosamidine is useful as a smooth muscle relaxant, vascular relaxant, vasodilator, blood flow enhancer, blood flow improver, prostate smooth muscle relaxant, and bladder smooth muscle relaxant. . The structural formula of isosamidine is represented by the following (Chemical Formula 1), and the CAS registration number is [53023-18-0].

  The smooth muscle relaxing action of the smooth muscle relaxant of the present invention is caused by, for example, causing the smooth muscle relaxant of the present invention to act on a blood vessel contracted with a vasoconstrictor such as phenylephrine as in Example 1 described later. It can be confirmed by testing whether or not the shrinkage is suppressed.

  In addition, the smooth muscle relaxing action of Poseidanocoumarin III (CAS registration number = [130464-57-2]) can be confirmed by the test method of the smooth muscle relaxing action described above. A smooth muscle relaxant containing Poseidanocoumarin III as an active ingredient is also an embodiment of the present invention. Poseidanocoumarin III can be extracted from buttonfish by the same method as isosamidin.

  Since the smooth muscle relaxant of the present invention has a relaxing action on vascular smooth muscle, it is particularly useful as a vasodilator. The smooth muscle relaxant of the present invention is effective as a vasodilator for the treatment of circulatory disturbance and hypertension due to blood flow stagnation. Moreover, the smooth muscle relaxant of this invention exhibits the improvement effect and the hair-growth effect of a cold syndrome as a blood flow increasing agent and / or a blood flow improving agent. That is, the coldness improving agent and / or hair restorer containing isosamidine is also an embodiment of the present invention.

  In addition, the smooth muscle relaxant of the present invention is useful as a prostatic smooth muscle relaxant in preventing or treating urination disorders due to prostatic hypertrophy. Furthermore, the smooth muscle relaxant of the present invention is useful as a bladder smooth muscle relaxant for the treatment of frequent urination and urinary incontinence and the improvement of the feeling of residual urine. The smooth muscle relaxant of the present invention is also useful as a prophylactic or therapeutic agent for other diseases caused by smooth muscle contraction, such as preterm labor, dysmenorrhea, and / or bronchial asthma.

  The isosamidine contained as an active ingredient in the smooth muscle relaxant of the present invention is not particularly limited to the present invention, but examples thereof are those derived from button fountain, and are described later in detail in “[3] Smoothness of the present invention”. What was obtained by the method of "the manufacturing method of a muscle relaxant" is illustrated. The isosamidine used in the smooth muscle relaxant of the present invention does not necessarily have to be isolated. For example, an extraction extracted from button bud using an aqueous solvent such as hydrous ethanol or an anhydrous alcohol such as anhydrous ethanol as an extraction solvent. The liquid or its concentrated dry product may be used as it is as the smooth muscle relaxant of the present invention.

  The smooth muscle relaxant of the present invention can also be produced by blending an isolated isosamidine or an extract derived from button buds containing isosamidine with a pharmaceutically acceptable liquid or solid carrier, Add solids such as tablets, granules, powders, powders, capsules, etc. if desired, with addition of solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, etc. Usually, it can be used as liquids, suspensions, emulsions and the like. Moreover, it can also be used as a dried product which can be made liquid by adding an appropriate carrier before use, and other external preparations.

  The carrier can be selected according to the administration form and the preparation form. In the case of an oral preparation comprising a solid composition, it can be a tablet, pill, capsule, powder, fine granule, granule, etc., for example, starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch Pharmaceutical carriers such as inorganic salts are used. In preparation of the oral preparation, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a corrigent, a colorant, a fragrance and the like can be further added. For example, in the case of a tablet or pill, if desired, it may be coated with a sugar coating such as sucrose, gelatin or hydroxypropylcellulose, or a film of a gastric or enteric substance. In the case of an oral preparation comprising a liquid composition, it can be a pharmacologically acceptable emulsion, solution, suspension, syrup, etc. For example, purified water, ethanol, etc. are used as a carrier. Is done. Further, if desired, auxiliary agents such as wetting agents and suspending agents, sweetening agents, flavoring agents, preservatives and the like may be added.

  On the other hand, in the case of a parenteral agent, the active ingredient of the present invention according to a conventional method is distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, It can be prepared by dissolving or suspending in polyethylene glycol or the like and adding a bactericidal agent, stabilizer, tonicity agent, soothing agent, etc. as necessary. In addition, a solid composition can be produced and dissolved in sterile water or a sterile solvent for injection before use.

  External preparations include solid, semi-solid or liquid preparations for transdermal administration or transmucosal (oral or intranasal) administration. Also included are suppositories and the like. For example, emulsions such as emulsions and lotions, tinctures for external use, liquid preparations such as liquids for transmucosal administration, ointments such as oily ointments and hydrophilic ointments, transdermal administration such as films, tapes, and poultices Or a patch for transmucosal administration.

  The content of isosamidine in the smooth muscle relaxant of the present invention is not particularly limited, and can be appropriately selected from the viewpoint of its functionality and activity expression. For example, in the smooth muscle relaxant, preferably 0.00001% by weight or more, more preferably Is 0.0001 to 10% by weight, more preferably 0.0006 to 6% by weight.

[2] Food or beverage of the present invention The food or beverage of the present invention contains the smooth muscle relaxant of the present invention. There are no particular limitations on the method for producing the food or beverage of the present invention, and for example, blending, cooking, processing and the like may follow those of general foods or beverages, and can be produced by those production methods. The smooth muscle relaxant of this invention should just contain in food or a drink. There is no particular limitation on the type of the food or beverage, for example, processed grain products, processed fats and oils, processed soybean products, processed meat products, marine products, dairy products, vegetables and the like, containing the composition of the present invention. Examples include processed fruit products, confectionery, alcoholic beverages, taste drinks, seasonings, spices, and other agricultural / forestry processed products, livestock processed products, and processed fishery products.

  The isosamidine, which is an active ingredient of the smooth muscle relaxant of the present invention, does not show toxicity even when an effective amount for the expression of its action is administered to a living body. Therefore, the smooth muscle relaxant of the present invention is suitable as a raw material for foods or beverages.

  The food or beverage of the present invention is effective in improving circulatory disturbance and hypertension due to blood flow stagnation, or dysuria, frequent urination, urinary incontinence, and residual urine feeling. That is, the food or beverage of the present invention is useful as a functional food (specific health food) intended to improve the above-mentioned symptoms, for example, “suitable for higher blood pressure”. It is extremely useful as a food for specified health use with a label.

  The content of isosamidine in the food or beverage of the present invention is not particularly limited, and can be appropriately selected from the viewpoint of its functionality and activity expression. For example, in food or beverage, preferably 0.00001% by weight or more, more preferably 0. 0.0001 to 10% by weight, more preferably 0.0006 to 6% by weight, and even more preferably 0.05 to 5% by weight.

  The food or beverage of the present invention comprises valyltyrosine, bonito oligopeptide, lactotripeptide, chunaka leaf extract, isoleucyltyrosine, wakame peptide, γ-aminobutyric acid (GABA), acetic acid, laver oligopeptide, royal jelly peptide, oolong It may further contain at least one health food material selected from the group consisting of tea flavonoids, casein decapeptides, and sesame peptides. Moreover, agaricus, tomorrow, tomorrow chalcone, astaxanthin, α-lipoic acid, agarooligosaccharide, ginkgo biloba, turmeric, elastin, L-carnitine, nucleic acid, chitosan, conjugated linoleic acid, glucosamine, coenzyme Q10, collagen, chondroitin, plant Sterol, Spirulina, Ceramide, Soy isoflavone, Togedocoro, Nattokinase, Garlic, Hyaluronic acid, Bilberry, Fucoidan, Propolis, β-glucan, Maca, Pine bark extract, Meshimakobu, Docosahexaenoic acid (DHA), Lutein, Cassis, Capsaicin, Ginger Further, at least one functional material selected from the group consisting of baboon, hesperidin, saw palmetto extract, pumpkin seed extract, pollen extract and lycopene may also be contained. That is, a food or beverage containing isosamidine and at least one health food material and / or functional material selected from the above group is one aspect of the present invention.

[3] Method for Producing Smooth Muscle Relaxant of the Present Invention The method for producing the smooth muscle relaxant of the present invention comprises (1) a step of washing the button bow with water, and (2) a button bow washed with step (1). In addition, the method includes a step of extracting isosamidine using hydrous alcohol as an extraction solvent. The inventors of the present invention have found that an extract containing isosamidine with high purity can be extracted by the above production method.

  As the button bow used in the present invention, the present invention is not particularly limited, but the fruit, seed, seed coat, flower, leaf, stem, root, rhizome and / or whole plant of the button bow must be used as it is. Among them, the leaf of a button bow can be preferably used. Moreover, although the present invention is not particularly limited, examples of the production area of the button bow fuu used in the present invention include Yakushima and Yonagunijima.

  The button bow can be used as a raw material for the method for producing the smooth muscle relaxant of the present invention even after harvested, but preferably, for example, a crushed material, a pulverized material or a mixture thereof, more preferably a treatment of these dry powders, etc. Things can be used. In the present specification, the pulverized product and the crushed material refer to, for example, those obtained by cutting a plant body or crushed after drying. Generally, a large particle size is referred to as a crushed material, and the particle size is small. Things are called crushed materials. In the present specification, the dry powder refers to a dry product having a smaller particle diameter than the pulverized product and the crushed product. The dried button-bow powder used in the following examples was prepared by cutting the washed raw button-bough leaves, drying them with hot air, and then crushing them.

  There is no particular limitation on the above-mentioned “(1) the step of washing the button fountain with water”, exposing the button fountain or a processed product thereof to running water, immersing the button fountain or the processed product in a container filled with water, etc. It can carry out by operation of. The amount of water used for washing is not particularly limited, but for example, 1 to 100 mL, preferably 5 to 60 mL, more preferably 10 to 40 mL is exemplified with respect to 1 g of dry powder of button bow leaf. Is done. There is no particular limitation on the temperature of the washing water, but water of 4 to 100 ° C. is usually used. The washing operation may be performed, for example, with stirring or standing, and may be repeated several times as necessary.

  The alcohol concentration of the hydrous alcohol used in the above “(2) Extracting isosamidine from the button fountain washed in the step (1) using the hydrous alcohol or anhydrous alcohol as an extraction solvent” is, for example, 20 to 90% by volume. And preferably 40 to 80% by volume, more preferably 60% by volume. Moreover, water-containing ethanol is illustrated as a water-containing alcohol, and anhydrous ethanol is illustrated as an anhydrous alcohol. Extraction can be performed batchwise or continuously by a known extraction method.

  The amount of the hydrous alcohol used as the extraction solvent is preferably 10 to 30 mL of extraction solvent, for example, per 1 g of dry powder of button bud leaves used as a raw material. The extraction temperature is preferably in the range of 4 to 60 ° C. The extraction time is usually set to be in the range of several seconds to several days, preferably 5 minutes to 24 hours. The extraction operation may be performed, for example, with stirring or standing, and may be repeated several times as necessary.

  By performing the above steps (1) and (2), it is possible to obtain an extract containing 30-60 mg of isosamidine per gram of dry weight.

  The method for producing a smooth muscle relaxant of the present invention may further include a step of subjecting the extract to filtration, centrifugation, concentration, ultrafiltration, and / or molecular sieving. By performing these treatments, an extract enriched in isosamidine can be prepared.

  For example, by carrying out the step of concentrating and drying the extract extracted by the above-mentioned “(2) step of extracting isosamidin from the button fountain washed in step (1) using water-containing alcohol as an extraction solvent”, It is possible to obtain a composition containing 30-60 mg of isosamidine per gram of solid matter.

  The method for producing a smooth muscle relaxant of the present invention may further include a step of fractionating the extract by fractionation operations such as fractional precipitation, column chromatography, thin layer chromatography and the like. By fractionation, a composition containing higher purity isosamidine can be obtained, and further, isolated isosamidine can be obtained. That is, the method for producing isosamidine comprising the steps of (1) washing the button fountain with water and (2) extracting the isosamidine from the button fountain washed in the step (1) using hydrous alcohol as an extraction solvent. This is one of the embodiments.

  Poseidanocoumarin III can also be produced by a method similar to the above-described method for producing isosamidine. That is, (1) a step of washing button bowfish with water, and (2) a step of extracting Poseidanocoumarin III from the buttonfish washed at Step (1) using hydrous alcohol as an extraction solvent. A manufacturing method is also one aspect of the present invention.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further more concretely, this invention is not limited to these description at all. In the examples, “%” means “volume%” unless otherwise specified.

Preparation Example Preparation of isosamidine from button fountain 10 L of 60% ethanol aqueous solution was added to 3 kg of button fountain dry powder, followed by extraction at 25 ° C. for 1 hour with stirring. After the extract and the residue were separated by suction filtration, the residue was extracted again using 10 L of 60% ethanol, and the extracts obtained by these two extraction operations were mixed. The obtained extract was concentrated to dryness, and the dried product was dissolved in 1 L of 60% ethanol aqueous solution. To this was added 2 L of 100% ethanol, mixed and allowed to stand to separate the supernatant and the precipitate. Furthermore, extraction / separation operation similar to the above from the precipitate was repeated 4 times using 2 L of 100% ethanol. The supernatants (extracts) obtained by these five extraction / separation operations were combined and concentrated to dryness, and then the dried product was dissolved in 1 L of 30% DMSO (dimethyl sulfoxide). Of the obtained DMSO solution, 150 mL was added to a Cosmo Seal (registered trademark) 140C18 column (manufactured by Nacalai Tesque) equilibrated with 20% ethanol aqueous solution, eluted with 2 L of 20% ethanol aqueous solution, and then 40% ethanol aqueous solution 4 Elute at 8 L. The eluate eluted with 40% ethanol aqueous solution was concentrated to dryness, and then the dried product was dissolved in 50 mL of 60% ethanol aqueous solution. Next, this solution was subjected to HPLC under the elution conditions shown in Table 1, and fractions eluted during a retention time of 57 to 62 minutes were collected and concentrated to dryness to obtain 1.31 g of isosamidine.

Example 1 Smooth muscle relaxant action of isosamidin A thoracic aorta was excised from an SD male rat (6-8 weeks old) and cut into a spiral shape to prepare a blood vessel specimen having a width of about 3 mm and a length of about 2 cm. The blood vessel specimen was suspended in Krebs buffer that had been aerated with 95% O ₂ -5% CO ₂ and kept at 37 ° C., and a tension of about 0.5 g was applied. The blood vessel contraction tension was recorded on a recorder via a transducer. After 10 ⁻⁷ M phenylephrine was added to the buffer solution to contract the blood vessel and the contraction reaction was stabilized, the isosamidine prepared in Preparation Example was added to the buffer solution to a final concentration of 1 μM. The ratio of the contraction tension that was suppressed after the addition to the contraction tension before the addition was calculated and used as a smooth muscle relaxing action. A similar experiment was performed for each case where isosamidine was added to a final concentration of 3 μM, 10 μM, 30 μM, and 100 μM. The results are shown in Table 2 and FIG.

  As shown in Table 2 and FIG. 1, it was revealed that isosamidine has a strong smooth muscle relaxing action and is useful as a vasodilator.

Example 2 Method for producing an extract containing isosamidine with high purity 40 g of distilled water was added to 2 g of dried button-bow powder and washed at 25 ° C. for 1 hour with stirring. After separating the extract and the residue by centrifugation, the same washing operation was repeated twice on the residue. To the obtained water washing residue, 40 mL of 20% aqueous ethanol solution was added as an extraction solvent, and extraction was performed at 25 ° C. for 1 hour with stirring. After the extract and the residue were separated by centrifugation, the same extraction operation as described above using a 20% aqueous ethanol solution as the extraction solvent was repeated twice for the residue. Extracts obtained by a total of three extraction operations were mixed and concentrated to dryness to obtain a water-washed residue → 20% ethanol extract. In addition, a 30% ethanol aqueous solution, 40% ethanol aqueous solution, 60% ethanol aqueous solution, 80% ethanol aqueous solution, or 100% ethanol was used as an extraction solvent in the same manner as above except that 20% ethanol aqueous solution was used. → 30% ethanol extract, water wash residue → 40% ethanol extract, water wash residue → 60% ethanol extract, water wash residue → 80% ethanol extract, and water wash residue → 100% ethanol extract, respectively did.

  As a comparison, 40 mL of 60% ethanol was added to 2 g of the dried button-bow powder, and extraction was performed at 25 ° C. for 1 hour with stirring. After separating the extract from the residue by centrifugation, the same extraction operation using a 20% aqueous ethanol solution as the extraction solvent was repeated twice for the residue. Extracts obtained by a total of three extraction operations were mixed and concentrated to dryness.

  The amount of isosamidine in the various extracts obtained was measured using HPLC to determine the content of isosamidine. Table 3 shows the analysis conditions by HPLC. In addition, the recovery rate of each extract was calculated when the recovery amount of isosamidine obtained by 60% ethanol extraction from button-blow dry powder not subjected to water washing as a comparison was 100.

  The results are shown in Table 4.

  As a result, by extracting the button-boiled fountain washed with water with an ethanol solution of 20 to 100%, an extract having an isosamidine purity of 5.4 to 8.5 times higher than that of the 60% ethanol extract is obtained. It became clear that It was also revealed that by extracting the button-washed fountain with water with 40-80% ethanol aqueous solution, an isosamidine can be obtained with a high recovery rate and an extract with a high purity of isosamidine can be obtained.

Example 3 Smooth muscle relaxant action of 60% ethanol aqueous extract of water-washed button fountain An extract was prepared in the same manner as the “water-washed residue → 60% ethanol extract” obtained in Example 2, Dissolved in 6 mL DMSO. This extract was tested for smooth muscle relaxing action in the same manner as in Example 1. The extract is added to the buffer so that the final concentration is 0.005%, 0.015%, 0.05%, 0.15%, 0.5%, and its smooth muscle relaxing action is achieved. confirmed. The results are shown in Table 5.

  As shown in Table 5, a strong smooth muscle relaxing action was observed in the 60% ethanol aqueous solution extract of water-washed button-bow.

Example 4 Inhibitory Effect of Isosamidin on Bladder Overcontraction Bladder was excised from a Japanese white male rabbit (17-29 weeks old) to prepare a slice specimen having a width of about 3 mm and a length of about 2 cm. The bladder slice specimen was suspended in Krebs buffer kept at 37 ° C. by aeration with 95% O ₂ -5% CO ₂ and a tension of about 1.0 g was applied. The contraction tension of the bladder section was recorded on a recorder via a transducer. Isosamidine was added to the buffer so that the final concentration was 30 μM or 100 μM, and then acetylcholine was added cumulatively until the final concentration was 10 ⁻² M to prepare a concentration-response curve. As a control, a test using a buffer solution without addition of isosamidine was also conducted. The results are shown in Table 6 and FIG.

  As shown in Table 6 and FIG. 2, isosamidine suppressed bladder contraction by acetylcholine in a dose-dependent manner, shifted the response curve to a higher concentration side, and suppressed maximum contraction.

Example 5 Inhibition of prostate contraction by isosamidin A prostate was extracted from a Japanese white male rabbit (17-29 weeks old) to prepare a slice specimen having a width of about 3 mm and a length of about 2 cm. The prostate section specimen was suspended in Krebs buffer that had been aerated with 95% O ₂ -5% CO ₂ and kept at 37 ° C., and a tension of about 0.5 g was applied. The contraction tension of the prostate section was recorded on a recorder via a transducer. Isosamidine was added to the buffer so that the final concentration was 30 μM or 100 μM, and phenylephrine was then added cumulatively until the final concentration was 10 ⁻⁴ M to prepare a concentration-response curve. As a control, a test using a buffer solution without addition of isosamidine was also conducted. The results are shown in Table 7 and FIG.

  As shown in Table 7 and FIG. 3, isosamidine suppressed the prostate contraction caused by phenylephrine in a dose-dependent manner, shifted the response curve to the high concentration side, and suppressed the maximum contraction.

  INDUSTRIAL APPLICABILITY According to the present invention, there are provided a composition useful for improving vascular function and preventing or treating a disease caused by smooth muscle contraction, and an efficient method for producing the composition.

Claims (9)

  A smooth muscle relaxant containing isosamidine as an active ingredient.   The smooth muscle relaxant of Claim 1 containing the water-containing alcoholic extract or anhydrous alcoholic extract derived from the button bowfish containing isosamidine.   The smooth muscle relaxant of Claim 2 containing the water-containing alcoholic extract derived from button bowfish.   The smooth muscle relaxant according to any one of claims 1 to 3, which is a vasodilator.   A food or beverage containing the smooth muscle relaxant according to any one of claims 1 to 3. It is a manufacturing method of the smooth muscle relaxant of Claim 1, Comprising: The method including the process of following (1)-(2):
(1) a step of washing the button bow with water; and (2) a step of extracting isosamidin from the button bow washed in step (1) using a hydrous alcohol or anhydrous alcohol as an extraction solvent.   The method of Claim 6 that the alcohol concentration of a hydrous alcohol is 40 volume%-80 volume%.   The method according to claim 6, wherein the hydrous alcohol is hydrous ethanol. A method for producing isosamidine, which comprises the following steps (1) to (2):
(1) a step of washing the button bow with water; and (2) a step of extracting isosamidin from the button bow washed in step (1) using a hydrous alcohol or anhydrous alcohol as an extraction solvent.

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