JP5690102B2 - Composition for preventing and treating urological diseases and method for producing the same - Google Patents

Description

  The present invention relates to a composition for preventing and treating urological diseases and a method for producing the same.

  The number of patients suffering from urination disorders in an aging society is increasing, and urination disorders are considered to be a potential social problem regardless of gender. The cause of the disease is not always clear and is often regarded as an aging phenomenon associated with aging rather than a disease. Although frequent urination and urinary incontinence do not present life-threatening symptoms, the patient's quality of life (QOL) is significantly reduced, resulting in mental and physical distress.

  Urination disorders include urine storage dysfunction and urine output dysfunction. Urinary dysfunction includes frequent urination and urinary incontinence (mainly urge incontinence and stress urinary incontinence). Urinary drainage dysfunction includes difficulty urinating, residual urine, urinary retention and the like. Although any pathogenic mechanism is classified into neurogenic and non-neurogenic, it is a pathological condition that ultimately shows excessive or incomplete contraction of bladder smooth muscle.

  Overactive bladder (immediate urinary incontinence) affects high morbidity and quality of life in both elderly men and women with dysuria in the elderly, prostate hypertrophy, a disease specific to elderly men, middle-aged and overwhelming women after menopause There are many cases of stress urinary incontinence. The number of overactive bladder patients is estimated to be approximately 8.1 million in Japan according to the 2002 Japan Urological Function Society survey. If stress urinary incontinence patients, which account for 70% of female urinary incontinence patients, are added to this, it is estimated that the number of patients suffering from dysuria is considerable.

  Examples of frequent urinary / urinary incontinence drug (urine accumulation dysfunction improving drug) include pharmaceuticals such as anticholinergic agents, bladder smooth muscle direct acting drugs, and various Chinese medicine preparations. Examples of low-activity bladder therapeutic agents (improving dysuria) include distigmine bromide and neostigmine bromide having cholinesterase inhibitory action, bethanechol chloride having muscarinic receptor activating action, and α1 adrenergic receptor antagonistic action. And uravidil.

  However, many side effects have been reported for any of these pharmaceuticals or Chinese medicine preparations. In addition, it is necessary to pay close attention to the interaction with medicines in Chinese medicine preparations. These pharmaceuticals or herbal medicines sometimes have serious side effects and are difficult to obtain and take easily because they are drugs that require a doctor's prescription. Many patients are hesitant to visit medical institutions because dysuria has no direct impact on life compared to other diseases. On the other hand, as a feature of the disease, it is important to take the drug continuously for a long period of time. In general, symptoms are reversed when the administration is stopped.

  Therefore, as a drug for preventing or improving urination disorder, a drug that can be surely expected to be effective, easily available, and can be safely taken for a long time is desired.

  Pepo Pumpkin Seed Formulation is on the market as one of the health supplements aimed at preventing or improving frequent urination and urinary incontinence. Containing components include those using seed oil, those using 60% alcohol extraction powder, or those using a mixture of both.

  As such a health food, for example, JP-A-2000-290192 contains a dried extract of pumpkin seeds and isoflavones as active ingredients, and the blending ratio of dried extract of pumpkin seeds: isoflavones is 99: 1-80. : A therapeutic agent for dysuria characterized by a weight ratio of 20 (patent document 1). JP-A-2005-343809 describes an inhibitor of urinary intention during sleep, which is obtained by blending 0.1 to 1 peppo pumpkin extract by weight ratio (Patent Document 2). Furthermore, JP-A-2001-342142 discloses a composition for preventing and treating urinary system diseases comprising (A) cranberry or an extract thereof and (B) pumpkin seed or an extract thereof. In addition to being excellent in improving urination abnormalities and urinary incontinence caused by symptoms, it is described that side effects such as stomach sag are reduced and the feeling of taking is good (Patent Document 3).

  As a typical preparation, a product using a dry extract (60% ethanol extract of peppo pumpkin seeds) is commercially available from Tervis Co., Ltd. (manufactured and sold) (Non-patent Document 1).

  In German Commission E monographs and the like, pepo pumpkin seeds are approved as an effective drug for hypersensitive bladder (frequent urination, urge urinary incontinence, residual urine sensation), particularly for female dysuria (Non-Patent Documents 2 and 3). ).

JP 2000-290192 A JP-A-2005-343809 JP 2001-342142 A

Sogabe Hitoshi, Terado Takashi, Medicinal Pepo Pumpkin Seed Extract and Soy Germ Extract Extract, General Clinical Trial for Night Frequent Urination, Medicine and Pharmacy, Natural Sciences, November 2001, 45, No. 5, p. 728-738 Mark Blumenthal, Werner Busse, Alicia Goldberg, Joerg Gruenwald, Tara Hall, Chance W. Riggins, Robert S. Rister, Sigrid Klein, "The Complete German Commission E Monographs", Published November 30, RevisedJanuary 17, 1991. "The American Botanical Council", Published incooperation with Integrative Medicine Communications, Boston, Massachusetts 1998, Pumpkin seed p.193

  The purpose of the present invention is to use pumpkin seeds (Cucurbita) seeds, dysuria derived from benign prostatic hyperplasia, frequent urination / urinary incontinence resulting from female climacteric disorder and stress urinary incontinence found in many women, The object is to provide a drug, beverage or food that is effective against overactive bladder or urinary dysfunction caused by urinary tract infections, which is recognized by both men and women, and can be taken safely and continuously for a long time.

  The present inventors have attempted to separate and purify a composition that can be reliably expected for urological diseases, can be easily obtained, and can be safely taken for a long time from seeds of Cucurbita pepo. . As a result, it was found that the composition obtained by water-extracting the seeds of Cucurbita pepo has a significantly stronger pharmacological activity than the conventionally reported 60% ethanol extract.

  The present invention has been made based on such findings, and provides a composition for preventing and treating urological diseases, which contains a water extract of pumpkin (Cucurbita) seeds as an active ingredient.

  In addition, the present invention is a tea bag in which the contents are stored in a bag, and the water-soluble components effective in preventing and / or treating urological diseases are eluted from the contents by immersing them in water. The content is to provide a tea bag in which the seed is a powder of Cucurbita seeds, and the seed is a powder in which the proportion of particles of 500 μm or less in the pulverized particle size is 50% by weight or more.

  The present invention also provides a composition for preventing and treating urological diseases, wherein water is used as an extraction solvent, and a water extract of the genus Cucurbita seed is obtained by immersing the genus Cucurbita seed in the extraction solvent. A manufacturing method is provided.

  The composition of the present invention is excellent in preventing urinary disorders such as dysuria resulting from benign prostatic hyperplasia, frequent urination / urinary incontinence resulting from climacteric disorder in women, and overactive bladder based on aging regardless of gender. Or exerts an improving action. In addition, unlike pharmaceuticals and herbal medicines, there are few side effects and long-term continuous use is possible. Because of its strong pharmacological activity compared to existing 60% alcohol extracts, high clinical effects can be expected with small doses. Furthermore, although 60% alcohol is used as an extraction solvent in the existing production method, the present invention is a new extraction method using water for extraction, has strong pharmacological activity, and can be produced easily and inexpensively.

It is a figure which shows the result of having examined the contraction inhibitory effect with respect to the urinary bladder smooth muscle of the composition for urinary system disease prevention treatment. It is a figure which shows the result of having examined the urination extension effect | action in the cystometrogram of the composition for urological disease prevention treatment. It is a figure which shows the urination extension action of the cystometrogram immediately after administration (post) and 30 minutes after administration (post30min.) Of the composition for preventing and treating urinary system diseases. 1 is a diagram showing a cystometrogram of a composition for preventing and treating urological diseases obtained in Production Example 1. FIG.

  The composition for preventing and treating urological diseases of the present invention contains a water extract of pumpkin genus (Cucurbita) as an active ingredient.

  In this embodiment, “water” means any of tap water, distilled water, purified water, ion exchange water, ultrafiltration water, reverse osmosis water, ultrapure water, and well water unless otherwise specified. To do.

  Specific urinary diseases include, for example, dysuria resulting from benign prostatic hyperplasia, frequent urination and / or urinary incontinence resulting from climacteric disorder in women, stress urinary incontinence often seen in women, Dysuria derived from overactive bladder and urinary tract infections, etc., which are effective against these.

  The composition for preventing and treating urological diseases of the present invention exhibits excellent preventive and / or therapeutic effects on these urological diseases, improves the quality of life (QOL) of the patient, Relieve emotional distress. In addition, unlike pharmaceuticals, herbal medicines, etc., there are few side effects and easy intake, so long-term continuous use is possible. Furthermore, since the pharmacological activity is stronger than that of the existing 60% alcohol extract, a high clinical effect can be expected even with a small dose. From the viewpoint of cost, there is also an advantage that the active ingredient can be extracted with water and can be manufactured easily and inexpensively.

  The seeds of the genus Cucurbita are not limited to their varieties, but are preferably seeds of pepo pumpkin (Cucurbita pepo) or western pumpkin (Cucurbita maxima).

  To obtain an aqueous extract of Cucurbita seeds, the entire Cucurbita seeds can be used. However, the preservation stability against oxidation of Cucurbita seeds and the ease of water extraction When considered, it is preferred to use defatted pumpkin seeds with a low fat content after oil is collected from Cucurbita seeds. Specifically, the fat content after removing the oil is preferably about 10% by weight or less of the seed weight, more preferably the seed of the genus Cucurbita from which the fat content is removed to about 1% by weight or less. .

  Moreover, in order to obtain the water extract of the genus Cucurbita, it is not limited to the shape of a seed. For example, pumpkin seeds with a thin outer skin may be used for extraction as they are, and those with a thick outer skin can be divided into more than 20%. Moreover, the squeezed rice cake which remained after the oil extraction of the pumpkin (Cucurbita) seed can also be used, and the pumpkin (Cucurbita) seed powder which grind | pulverized it can also be used. The particles should be as coarse as possible considering the oxidative stability of the fats and oils contained in the seeds of the genus Cucurbita, but it is desirable that the particles be fine to some extent when considering the extraction efficiency of the active ingredient. Specifically, the proportion of particles of 500 μm or less in the pulverized particle size is preferably 50% by weight or more.

  It is preferable that the pumpkin (Cucurbita) seed used in the present embodiment has been sterilized. The sterilization treatment can substantially sterilize Gram-negative pathogenic bacteria (for example, Salmonella), so that safety as a composition for preventing and treating urological diseases can be improved.

  Specifically, for example, a sterilization treatment can be performed by passing a pumpkin seed, a defatted pumpkin seed or a pumpkin seed powder through superheated steam at 110 ° C. for several seconds with a superheated steam sterilizer. Moreover, it can also sterilize using a microwave sterilizer.

  The pumpkin seed (Cucurbita) seed, defatted pumpkin seed or pumpkin seed powder used in the present invention needs a heat history at 55 ° C. for 10 minutes or under a moist heat equivalent to or higher than that for pathogenic bacteria, and water extraction Measures against microbial growth during the manufacturing process such as 80 ° C., 30 minutes or equivalent or less under humid heat as the upper temperature condition to prevent the prevention and / or treatment effect activity against urological diseases A thermal history is preferred. If a heat history exceeding this range is given, the preventive and / or therapeutic effect on urological diseases may be reduced.

  Since the composition for preventing and treating urological diseases of the present invention is obtained by water extraction, it can be used as a liquid, but it can also be dried to give a dry powder. For drying the water extract, either freeze drying or spray drying can be selected.

  There is no restriction | limiting in particular as a form of the composition for urinary system disease prevention treatment of this invention, It can provide as a pharmaceutical, a drink, or a foodstuff. Examples of the pharmaceuticals include powders, fine granules, tablets, coated tablets, capsules, syrups, and drinks containing the composition for preventing and treating urological diseases of the present invention. Examples of the beverage include hydration drinks filled in containers such as cans, plastic bottles, bottles and paper containers containing the composition for preventing and treating urinary system diseases of the present invention, and the composition for preventing and treating urinary system diseases of the present invention. Can be made into a tee bag filled with a nonwoven fabric or the like. Examples of foods include health supplements and food materials containing the composition for preventing and treating urological diseases of the present invention. In addition, since the composition for preventing and treating urological diseases of the present invention contains fat, for example, in the case of tailoring a tea bag with a long shelf life of more than six months, a packaging bag that can be sealed even with low fat. It is preferable to accommodate it together with an oxygen scavenger. In addition, the packaging bag may be a packaging bag in which the above tea bags are individually mounted, or a packaging bag in which a plurality of tea bags are accommodated.

  Regardless of pharmaceuticals and health supplements, excipients such as corn starch, lactose, crystalline cellulose, sucrose fatty acid esters, binders, disintegrants, lubricants, etc. are added to the above dosage form components as necessary. You can also.

  In the case of the beverage, for the purpose of enhancing palatability and functionality, pigeons, oolong tea, hub tea, hawthorn, malt, strawberry tea, amadokoroko, gymnema sylvestre, safflower, daidai, green tea, brown rice, oolong tea, kelp, wormwood, spirit Shiba, wolfberry, bear moth, bamboo leaf, shiitake mushroom, mandarin orange peel, Seiko (Ebisu grass seed), beach tea, Morohaya, Tochu Nakaba, licorice, Biwa leaf, banca, ginseng, rooibos, messy, too much, Roasted green tea, Pu'er tea, Golden flower tea, Green tea extract, Beaked fruit, Ginger, Jujube, Light load, Evening primrose, Guava leaf, Banaba leaf, Orchard spruce, Shrimp, Morohaya, Psyllium, Artemisia, Arachnid leaf, Mulberry leaf, Ginkgo, Honeysuckle, Oyster, Mate leaf, Vulture, Perilla, Artichoke, Echinacea, Elderflower, Oregano, Orange peel, Range Blossom, Chamomile, Cardamom, Clove, Kwan Grass, Gentian Shoko, Comfrey, Saflower, Summer Savory, Sisium, Cinnamon, Jasmine, Juniper Berry, Stevia, Sage, Serpyrum, St Johns, Turmeric, Thyme, Thyme, Dandelion, Nettle, Hibiscus , Basil, passion flower, vanilla beans, valerian, hyssop, fever fu, fennel, hop, marjoram, marigold, mallow, peppermint, meadowweed, yarow, eucalyptus, lavender, licorice, linden, lemongrass, lemon verbena, lemon balm, One or more of lemon peel, rose, rose hips, rosemary, wild strawberry, etc. can be combined.

  The daily dose for adults of the composition for preventing and treating urological diseases of the present invention is preferably 500 mg to 1000 mg in terms of solid content. It is recommended to take 1 to 3 doses after meals.

  The method for producing a composition for preventing and treating urological diseases according to the present invention uses water as an extraction solvent, and immerses the Cucurbita seed in the extraction solvent to obtain an aqueous extract of the Cucurbita seed. To get.

  Conventionally known methods for extracting the active ingredient of the genus Cucurbita are mainly lipophilic fractions such as fatty acids (linoleic acid, oleic acid, palmitic acid), carotenoids, tocopherols, Δ-5 and Δ-7 phytosterols. An aqueous ethanol solution was used as the extraction solvent to extract the minutes. On the other hand, the present invention finds that the active ingredient is contained in the water-soluble fraction, and uses water as an extraction solvent to produce a composition having excellent preventive and / or therapeutic effects on urological diseases. To do.

  In producing a composition for preventing and treating urological diseases, which is a raw material for the contents, defatted pumpkin seeds after extraction are extracted with an aqueous solvent. The extraction temperature can be applied in a wide range from a low temperature to a high temperature (for example, 5 to 80 ° C.), preferably room temperature (around 25 ° C.). The extraction operation is not particularly limited in the mass extraction of the content material.

  In the method of wrapping pumpkin seeds (Cucurbita) seeds or pulverized pumpkin seeds (Cucurbita) seeds in a tea bag and extracting them with a pot of water for a certain period of time, it is preferably packed in a convenient tea bag and heated with hot water or There are a method of extracting the beverage for a short time with warm water to make a beverage, and a method of immersing it in water for several hours to make a cold water tea beverage.

  The extraction solvent may further contain salts. However, when extracting with the aqueous solution which added salt, it is preferable to remove salt by desalting operation depending on the density | concentration of salts.

  Other matters are the same as those described in the above-mentioned composition for preventing and treating urological diseases.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited to this at all.

1. Pretreatment of genus Cucurbita Cucurbita pepo seed was used as the genus Cucurbita. First, 1 kg of pepo pumpkin seeds were crushed. Next, water and a small amount of sodium chloride were added to the crushed material and kneaded and heated at 140 ° C. for 30 minutes. And the defatted pumpkin seed was obtained by pressurizing a crushed material with a press machine and extracting water and oil.

  This defatted pumpkin seed was dried and applied to a pulverizer to obtain a powdered powder in which the proportion of particles of 500 μm or less in the pulverized particle size was 50% by weight or more (hereinafter referred to as “low-fat pumpkin seed powder”) Called). By these operations, about 320 g of pumpkin seed oil and 430 g of low fat pumpkin seed powder were obtained. This low fat pumpkin seed powder was subjected to the next step. Thereafter, a low-fat pumpkin seed powder was prepared by the same method as necessary.

2. Production of Composition for Preventing and Treating Urological Diseases The low-fat pumpkin seed powder prepared in 1 above was subjected to solvent extraction under the conditions shown in Table 1 below to produce a liquid composition for preventing and treating urological diseases. In Production Example 1, an extract of 400 g to 32 g of low-fat pumpkin seed powder was obtained. Similarly, in Production Example 2 and Comparative Example 1, 36 g and 20 g of extract could be obtained, respectively. In Production Example 3, 1.5 kg of extract could be obtained from 20 kg of low-fat pumpkin seed powder. The drying treatment was freeze-dried in Production Examples 1 and 2 and Comparative Example 1, and spray-dried in Production Example 3.

3. Evaluation Test (1) Pharmacological Activity-1 (Evaluation Example Using Rabbit Bladder Smooth Muscle Specimen)
Using the composition for preventing and treating urological diseases of Production Example 1 and the 60% ethanol extract of Comparative Example 1 as test substances, the effect of suppressing contraction of rabbit bladder smooth muscle was evaluated in the following manner.

  The evaluation test uses a method of using bladder smooth muscle specimens used as a method for evaluating the efficacy of drugs for dysuria and functional foods (Food Functional Research News No. 22, Issued on March 19, 2007, Inc. Mercian Clintech Environmental Inspection Department) was used.

  The method using bladder smooth muscle specimens is an in vitro test method using isolated smooth muscles (bladder, ileum) of rabbits, rats, guinea pigs, etc., and agonists for muscarinic receptors present on the membrane surface of bladder smooth muscles To examine the inhibitory action as an antagonist of the drug.

  In urinary bladder smooth muscle, acetylcholine released from nerve endings upon activation of parasympathetic nerves binds to muscarinic receptor (M receptor), and smooth muscle contraction is induced. This study is a muscarinic receptor agonist. This study examines the inhibition of contraction against smooth muscle contraction induced by carbachol (Carbachol: an alternative to acetylcholine) using the action of the muscarinic receptor blocker Atropine.

  Atropine suppresses carbachol contraction in a dose-dependent manner and translates its concentration-response curve to the right. This mode of inhibition by atropine is called antagonistic inhibition by muscarinic receptor blockade, and a substance that relaxes bladder smooth muscle by the same mode of action as atropine is called an anticholinergic agent.

  When the test substance exerts an inhibitory effect on the contraction caused by carbachol on the isolated bladder smooth muscle in the same manner as atropine, and the concentration-response curve is translated to the right, the test substance acts on the bladder smooth muscle. It is presumed that the contraction by carbachol via the muscarinic receptor was suppressed and relaxed by antagonistic inhibition.

  On the other hand, if the test substance inhibits carbachol-induced contraction of bladder smooth muscle but the inhibition is not complete and the concentration-response curve is not translated to the right, the test substance will not react with carbachol against the muscarinic receptor. By acting non-antagonistically on the reaction, it is presumed that the contraction caused by carbachol was suppressed and relaxed.

  The rabbit was lethal to death under anesthesia by intravenous administration of sodium pentobarbital, then laparotomized, urine was aspirated from the bladder with a syringe, and the bladder was removed. The fat around the excised bladder was carefully removed and then placed in a nutrient solution to prepare a specimen from the bladder body. These specimens were suspended with a load of 1 g and left for about 1 hour to stabilize. Contractile force was recorded isometrically on a polygraph (RM-6000, Nihon Kohden) via an FD pickup (TB-611T, Nihon Kohden) and a strain pressure amplifier (AP-621G, Nihon Kohden).

Carbachol (CCh: 10 ^{−8 to} 3 × 10 ⁻⁶ M) was cumulatively added to prepare a CCh concentration-contraction response curve. Thereafter, the inside of the bath was washed three times with a nutrient solution and stabilized for 30 minutes, and then a CCh concentration-contraction response curve was prepared again.

  Next, a physiological saline solution as a solvent was added into the organ bath and pretreated for 20 minutes, and then a CCh concentration-contraction response curve was prepared and used as a control. Thereafter, a test substance (6 mg / ml) was added and pretreated for 20 minutes, and then a CCh concentration-contraction response curve was prepared (n = 5).

  The contraction rate (%) after addition of the test substance was calculated with the control CCh concentration-shrinkage response curve maximum contraction rate of 100%. Inhibition rate = control 100%-contraction rate after addition of the test substance (%) Calculated as

  The results are shown in FIG. The inhibition rate was 41.3% on average for the composition for preventing and treating urological diseases obtained by water extraction in Production Example 1, and 29.4% on average for the 60% ethanol extract obtained in Comparative Example 1. The composition for preventing and treating urinary diseases showed higher inhibition rate than 60% ethanol extract. Therefore, it was found that more active ingredients are contained in the hydrophilic component contained in the water extract of pepo pumpkin (Cucurbita pepo) seeds.

(2) Pharmacological activity-2 (evaluation example by cystometrogram)
Using the composition for preventing and treating urological diseases of Production Example 1 and the 60% ethanol extract of Comparative Example 1 as test substances, the urination interval extending action was evaluated in the following manner.

  The evaluation test is a cystometrogram / intravesical pressure measurement method (medicine and pharmacology, 54 (3), p339-345, (2005) and Biomedical Research, which is used as a method for evaluating the efficacy of drugs for dysuria and functional food materials. , P29-33, (2005)).

  The cystometrogram / intravesical pressure measurement method enables comprehensive observation of the bladder function including the bladder, urethra, and micturition reflex center, and thus is widely used for evaluating the efficacy of therapeutic agents for dysuria using anesthetized animals.

  This test method involves incising the rat's abdomen after anesthesia, attaching a transducer for measuring intravesical pressure and a drug infusion pump, recording changes in the internal pressure of the bladder before and after administration of the test substance on a polygraph, and affecting the intravesical pressure. The action of the test substance is traced over time. When the test substance acts on the bladder to reduce irritation to the bladder smooth muscle, the internal pressure of the bladder decreases and the amount of urine stored in the bladder increases. As a result, the urination interval is extended and the number of urinations is decreased.

  The degree of improvement for shortening the urination interval and reducing the urination threshold pressure using the urination interval, the urination threshold pressure (internal pressure before the start of urination contraction) and the maximum urination contraction pressure (maximum internal pressure during urination contraction) as indicators. Then, statistically analyze the effect on the maximum micturition contraction pressure, etc., and evaluate the effectiveness of the test substance against frequent urination and urinary incontinence associated with overactive bladder from the test results based on it.

  Rats were anesthetized by intraperitoneal administration of sodium pentobarbital, then the midline of the lower abdomen was opened and polyethylene tubes were inserted into the ureters on both sides, and the generated urine was drained out of the body. The bladder was exposed, and an injection needle with a silicone tube filled with physiological saline was inserted from the top of the bladder. After the insertion site was ligated, the silicone tube was led out of the body.

  The silicon tube was connected to a polyethylene tube, and connected to an infusion pump in which a strain pressure transducer and a syringe filled with physiological saline were set via a three-way cock. Stabilized for about 30 minutes after connection.

  Urination was induced by continuous infusion of physiological saline into the bladder at a flow rate of 3 mL / hr. The intravesical pressure curve obtained by continuous infusion was recorded on a linear coder through a strain amplifier. The test substance observed the urination pattern for 15 minutes from the start of solvent injection, and 10 mg / kg was administered from the jugular vein (n = 3) when the difference between the three urination intervals before the administration reached within 2 minutes.

  The result is shown in FIG. The composition for the prevention and treatment of urinary system diseases in Production Example 1 showed an average urination interval extending action of 69%, whereas the 60% ethanol extract of Comparative Example 1 produced an average of 24% extension action. The composition for preventing and treating urological diseases obtained from 1 showed a higher urination interval extending action than the 60% ethanol extract obtained in Comparative Example 1.

(3) Pharmacological activity-3 (Example of evaluation by cystometrogram)
Using the composition for preventing and treating urological diseases of Production Example 1 and the 60% ethanol extract of Comparative Example 1 as test substances, the urination interval extending action was evaluated in the following manner.

  Using the same technique as in (2) above, 100 mg / kg of the composition for preventing and treating urinary system diseases in Production Example 1 was administered to a low pH stimulated frequent urine model rat in which physiological saline was changed to 0.2% acetic acid physiological saline. (N = 2).

  The results are shown in FIG. In low pH stimulated frequent urination model rats in which physiological saline was changed to 0.2% acetic acid physiological saline, 100 mg / kg of the urinary tract disease prevention / treatment composition of Production Example 1 was administered, and an average of 51.2 immediately after administration (post) % Urination interval prolongation effect was observed, and an average urination interval prolongation effect of 33.0% was observed 30 minutes after administration (post30min.).

  Furthermore, the urination threshold pressure was increased by an average of 44.3% immediately after administration and an average of 17.7% 30 minutes after administration. Moreover, there was no effect on the micturition contraction pressure, which is thought to lead to an increase in residual urine if decreased.

  Therefore, it was suggested that the composition for preventing and treating urinary tract diseases of Production Example 1 suppresses excessive bladder smooth muscle contraction during urine accumulation without decreasing the bladder contraction pressure during urine drainage.

  In the yield comparison, the urinary tract disease prevention / treatment composition of Production Example 1 was 8.0%, and the 60% ethanol extract of Comparative Example 1 was 5.0%, showing a higher yield of the urinary tract disease prevention / treatment composition. . In terms of properties, the composition for preventing and treating urological diseases was much less hygroscopic than the 60% ethanol extract, and was easy to handle.

(4) Clinical trial example 1
Pepo pumpkin (Cucurbita) prepared in 1 above
pepo) 5g of low-fat pumpkin seed powder in a non-woven tea bag, pour 180ml of hot water and steam for 30 minutes or more to elute the water-soluble components of the low-fat pumpkin seed powder into hot water. Prepared a composition for preventing and treating urinary system diseases (pepo pumpkin tea). Take the tea to four middle-aged men aged 65 to 75 who have overactive bladder symptoms (frequent urinary symptoms) each with 2 or more nightly urinations for 4 days and drink about 180 ml in total before going to bed. received.

  As a result, the number of urinations during the night was improved in the 2 patients from the first day (the number of urinations during the night decreased by 1 or more), and the other 2 patients did not change. Furthermore, on the 3rd and 4th day of taking the drug, the improvement in the number of urinations during the night was confirmed in all four patients, and the effect of improving the urinary excretion during urination was also observed. In addition, the method of administration seen in this clinical trial has also demonstrated that the drug effect by the water extract is immediate.

(5) Clinical trial example 2
A preparation containing 100 mg of the urinary tract disease prevention and treatment composition obtained in Production Example 3 in one capsule and a preparation containing 100 mg of the 60% alcohol extract obtained in Comparative Example 1 in one capsule were prepared. .

  Twelve people with overactive bladder symptoms (frequent urination symptoms) with urination frequency of 2 or more at night were randomly divided into 6 groups of A and B, and the urology obtained in Production Example 3 for A group A preparation containing a composition for systemic disease prevention and treatment was administered, and a preparation containing a 60% alcohol extract obtained in Comparative Example 1 was administered to Group B.

  Both doses / methods were 5 capsules immediately after dinner every day. As a result of measuring the total number of urination during night sleep for 5 days after the start of administration, the total for Group A was 37 (1.23 times / person per night), and that for Group B was 47 (1.57 / person). there were. Also in this clinical trial, it was found that the urinary tract disease prevention / treatment composition obtained in Production Example 3 was more effective against frequent urination than the 60% alcohol extract obtained in Comparative Example 1. There were no side effects in either group.

Claims (10)

  A composition for preventing and treating urological diseases, comprising a water extract of Cucurbita seed as an active ingredient.   The composition for preventing and treating a urological disease according to claim 1, wherein the seed of the genus Cucurbita is a seed of Cucurbita pepo.   The composition for preventing and treating a urinary system disease according to claim 1 or 2, wherein the seed is a seed after oil extraction.   The composition for preventing or treating a urinary system disease according to any one of claims 1 to 3, wherein the seed is a powder in which a proportion of particles of 500 µm or less in a pulverized particle size is 50% by weight or more.   The urological disorder is dysuria resulting from benign prostatic hyperplasia, frequent urination and / or urinary incontinence resulting from climacteric disorder in women, overactive bladder, stress urinary incontinence, dysuria resulting from urinary tract infection The composition for preventing or treating a urinary system disease according to any one of claims 1 to 4.   A method for producing a composition for preventing and treating urological diseases, wherein water is used as an extraction solvent, and a water extract of the genus Cucurbita is obtained by immersing the cucurbita seed in the extraction solvent. The method for producing a composition for preventing and treating urological diseases according to claim 6 , wherein a seed of cucurbita pepo is used as the seed of the genus Cucurbita. The method for producing a composition for preventing and treating urological diseases according to claim 6 or 7 , wherein the fat content of the seed is 10% by weight or less. The method for producing a composition for preventing and treating urological diseases according to any one of claims 6 to 8 , wherein the seed is a powder in which the proportion of particles having a pulverized particle size of 500 µm or less is 50 wt% or more. The urological disorder is dysuria resulting from benign prostatic hyperplasia, frequent urination and / or urinary incontinence resulting from climacteric disorder in women, overactive bladder, stress urinary incontinence, dysuria resulting from urinary tract infection the method urological disease prevention therapeutic composition according to any one of claims 6-9.