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WO2019009354A1 - Composition pour l'amélioration de la dysurie - Google Patents

Composition pour l'amélioration de la dysurie Download PDF

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Publication number
WO2019009354A1
WO2019009354A1 PCT/JP2018/025478 JP2018025478W WO2019009354A1 WO 2019009354 A1 WO2019009354 A1 WO 2019009354A1 JP 2018025478 W JP2018025478 W JP 2018025478W WO 2019009354 A1 WO2019009354 A1 WO 2019009354A1
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WO
WIPO (PCT)
Prior art keywords
composition
extract
urination
bladder
disorder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2018/025478
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English (en)
Japanese (ja)
Inventor
済泰 禹
公男 菅谷
さおり 西島
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Okinawa Research Center Co Ltd
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Okinawa Research Center Co Ltd
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Priority to JP2019527763A priority Critical patent/JPWO2019009354A1/ja
Publication of WO2019009354A1 publication Critical patent/WO2019009354A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/121—Ketones acyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • A61K35/768—Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder

Definitions

  • the present invention relates to a composition for improving urination disorder.
  • the bladder of a healthy person can store up to 300-500 ml of urine.
  • a signal related to urination is sent to the brain and the first urination is felt.
  • the parasympathetic nerve is excited and as a result, the muscarinic receptors of the bladder are stimulated and the smooth muscle (detrusor muscle) contracts.
  • the sympathetic nerve is dominant and the detrusor muscle is in a relaxed state.
  • OAB is a disease in which the bladder in the storage stage responds excessively, resulting in sudden and strong urination, and it has been reported that its prevalence increases with age.
  • sympathetic and parasympathetic nerves break down, and urination and frequent urination occur due to involuntary contraction of the detrusor muscle regardless of urine storage.
  • OAB has been reported to be associated with prostatic hyperplasia.
  • the prostate is located just below the bladder and surrounding the urethra. When the prostate enlarges with age, the urethra at the outlet of the bladder is compressed, causing "reduction of urine" and "feeling of residual urine”.
  • Urination disorder can be said to be an age-related disease that develops due to various factors in the range from the bladder to the urethra. Therefore, preventing urination disorder is extremely important to live a comfortable elderly person's life.
  • Non-patent Document 1 the entire description of the document is incorporated herein by reference.
  • long-term use of commercially available anticholinergic drugs has a risk of side effects.
  • composition containing nobiletin, tangeretin, 3 ', 4', 5,7-tetramethyl quercetin and sinensetin described in Patent Document 1 is mainly obtained from extracts using the peel of Shikuwasa in citrus fruits.
  • production areas such as Shikuwasa are limited, and there is a need for raw materials that can be obtained more easily.
  • the present invention is effective in preventing urination as compared with the natural product containing nobiletin etc. described in Patent Document 1, but it is possible that the urination disorder includes a component derived from a natural product which can be obtained easily and in large quantities. It is an object of the present invention to provide a composition for improvement.
  • Raspberry ( Rumex ) is a perennial herb of the family Rade ( Rumex ), and R. japonicus , R. crispus , R. obtusifolius, R. maritimus etc. are known. . Gishigishi is a perennial plant distributed all over Japan, and is a natural product that can secure a sufficient supply.
  • anchovy extract contains various components, among which nepogin and its analogues are mainly contained in a large amount.
  • nepogin (CAS registration number: 3785-24-8) is also referred to as mucidin or dianeridin, and has a structure represented by the following formula (1).
  • AMPK 5 'adenosine monophosphate activated protein kinase
  • the extract of Musk has urination disorder, eg, urge incontinence from overactive bladder, urination frequency during the daytime, urination frequency during the night, urgency frequency and urination frequency from the prostate hypertrophy during the day, urination frequency during the night, urgency feeling It is not known at all that it is extremely effective in improvement such as residual urine, poor appearance, and bladder outlet obstruction and reduction in urethral closure pressure, which is a new finding of the present inventors. .
  • the present invention is an invention that has been completed based on these findings and successful examples.
  • compositions [1] to [7] are provided.
  • a composition for ameliorating urination disorder which comprises an extract of moth extract as an active ingredient.
  • the logbook extract contains constructivegin, nepogin analogue and / or anthraquinones as an active ingredient.
  • the above urination disorder is at least one selected from the group consisting of pollakiuria, nocturia, urinary incontinence, residual urine, decreased urinary retention, reduced bladder contraction, bladder outlet obstruction and reduced urethral closure pressure.
  • composition according to [1] or [2], which is a voiding disorder of [4] The composition according to any one of [1] to [3], which is a composition for ameliorating urination disorder for oral use.
  • a method for ameliorating urination disorder comprising the step of ameliorating urination disorder in the individual by administering the composition according to any one of [1] to [6] to the individual.
  • composition of one aspect of the present invention it is possible to produce a whole country from the whole country and process as an active ingredient an extract obtained by processing a large amount of easy to obtain an extract as compared with the prior art. It is possible to produce products for improving urination disorders of industrial scale and economically superior.
  • the berry extract used as an active ingredient in the present invention is taken when taking a long time characteristic of the treatment for urination disorder Even if it is possible to use it with reduced side effects.
  • the composition according to one aspect of the present invention may be effective against a pelvic congestion model, which is one of the causes of frequent urination in women due to lower urinary tract disorders among urination disorders, and thus the potential demand is extremely high. It has the convenience that it can be taken easily at the time of treatment.
  • FIG. 1 is a view showing the effect of intravenous administration of a extract of Gishigiri on continuous intravesical pressure measurement (bladder contraction interval) of pelvic congestion frequent urination rats in an example described later.
  • FIG. 2 is a view showing the frequency of nocturnal urination at night in a patient with pelvic congestion frequent in the examples described later.
  • composition which is one aspect of the present invention is a composition for ameliorating urination disorder containing an extract derived from berry as an active ingredient.
  • Gishigishi is a kind of generally known family Tadeaceae plant, and is, for example, a perennial plant distributed all over Japan, and it is known as a weed often found in roadsides and ridges of paddy fields. Gishigishi is also known as a plant that spreads a stem about 1 m in early summer and gives a flower resembling buckwheat to a bell.
  • the resin such as, for example, Rumex japonicus, R. crispus, R. obtusifolius, R. gmelini, R. nepalensis, R. hastatus, R. alpinus, sorrel (R. acetosa), R. a. cripus, R. stenophyllus, R.S. patientia, R .; chalepensis, R. Orientalis etc. are mentioned.
  • Gigirs include plants closely related to Gishi.
  • plants that are closely related to Gishigishi include Dianella ensifolia, which is a plant that is closely related to a plant of the family Tadeidae. revoluta, D. callicarpa D. nigra; Hemerocallis minor; Simethis bicolor Kunth, which is a family of Rhizophoraceae; Limonium myrianthum, which is an isomatsuaceae isopus genus plant; Rhamnus prinoides, which is a family of Euphorbiaceae; wightii, R. procumbens; Myrsine africana, which is a genus of Ruminaceae, and other plants such as Maesopsis eminii, but not limited thereto.
  • the site of the hook is preferably a root.
  • roots In addition to roots, it may be mixed with other parts such as stems, leaves and flowers.
  • gussula sieboldii are as follows: gussula sieboldii, scutellaria vulgaris, scutellaria s. hastatus, D. ensifolia, D. callicarpa (Liliaceae), D. R. nigra, H. vulgaris and Myrsine africana roots; leaves of Prinoides; such as bark of wightii.
  • the root of berry root is preferred because it has been used as a herbal medicine in the name of ovine.
  • chrysophanol, emodin, chrysophanoanthrone, oxalic acid, etc. are contained in the roots of snail, and it is known that they have an antibacterial action and a coagulant action.
  • the extract of spinach there is no particular limitation on the extract of spinach as long as it exhibits an action to improve urination disorder.
  • the extract of the abalone which is obtained by the process of extracting a high content of nepogin, nepogin analogue and / or anthraquinones, causes urination as described below. Since it exerts the effect of improving the disorder, it can be assumed that nepogin and its analogues and anthraquinones, among them, a high content of nepogin exerts the effect of improving urination disorder. Therefore, it is preferable that the anchovy extract is an anchovy extract containing constructivegin, nepogin analogues and / or anthraquinones, and more preferably an anchovy extract containing constructivegin.
  • Examples of the volleyballgin analogues include nakahalene etc. shown in the following formula (2).
  • Examples of anthraquinones include emodin, chrysophanol, physcion and the like.
  • the extract of Neemaria japonicum contains a high concentration of nepogin.
  • the nepogin concentration (content) in the extract is not particularly limited.
  • nepogin is at least 10 wt%, preferably at least 20 wt%, more preferably at least 30 wt%, based on the dry weight of the extract.
  • the nepogin analogue nakahalene may be contained in an amount of about 1 to 15 wt%, preferably 10 wt% or less, and anthraquinones emodin, chrysophanol, physcion, etc. in an amount of about 1 to 10 wt%, Preferably, it may be contained at 8 wt% or less.
  • a method for producing a romancegin-containing anchovy extract and the like comprising the following steps (1) to (5) can be mentioned: (1) a step of obtaining a crude extract of a moth by subjecting the moth to an extraction treatment using a nepogin soluble solvent; (2) a step of obtaining a crude extract of the crude extract of Gishigishi by subjecting the crude extract of the Gishigishi extract to a hydrolysis treatment and / or a concentration treatment; (3) a step of obtaining a weakly alkaline insoluble matter by subjecting the above crude extract of crude extract to a weakly alkaline treatment; (4) a step of obtaining a strong alkali solution by subjecting the weak alkali insoluble matter to a strong alkali treatment; and (5) a nepogin-containing glutinous
  • the fine roots are removed from the roots of the moss which was dug up when the flower stems die (July-September), dried in sun, and dried thoroughly. 2 to 10 times by mass of ethanol is added to the roots of the dried graminea to which a predetermined amount was weighed, and extraction treatment is carried out by allowing the mixture to stand at room temperature for 5 to 15 hours.
  • the crude extract is obtained by removing the residual residue by means of solid-liquid separation.
  • a weak alkali treatment is carried out using 0.05 to 1% (w / v) a weakly alkaline aqueous solution (pH 8 to 10) on the solid content of the crude extract of the hardwood which has been obtained By removing the lysate, a weakly alkaline insoluble is obtained.
  • the obtained weakly alkaline insoluble matter is subjected to a strongly alkaline treatment using a 0.05-1% (w / v) strongly alkaline aqueous solution (pH 12 to 14), and the strongly alkaline By removing the lysate, a strong alkaline lysate is obtained.
  • the obtained strong alkaline solution is neutralized using an acid (pH 1 to 3) such that the pH of the solution becomes 7 to 8, and the solution for neutralized solution is dissolved by solid-liquid separation means By removing the extract to give a fresh extract.
  • an acid pH 1 to 3
  • the structure can be determined by subjecting the obtained mass spectrometry (MS), nuclear magnetic resonance analysis (NMR) and the like to obtain various spectrum data and comparing them with literature values.
  • MS mass spectrometry
  • NMR nuclear magnetic resonance analysis
  • the composition of one embodiment of the present invention has a urination disorder ameliorating effect.
  • voiding disorder means that difficulty in urination is recognized as a subjective symptom or as a result of a suitable test in a subject, where the difficulty in urinating is symptoms of excretion and urine collection. It includes any condition in which any inconvenience associated with urination has occurred, including symptoms.
  • Urination disorder can be said to be lower urinary tract dysfunction.
  • discharge symptoms mainly refer to urine discharge disorders, and are states in which urine decline, urinary line disruption, urination delay, urinary retention, residual urine feeling and the like occur.
  • compositions of the present invention are directed to at least any one of these types of dysuria. As described below, these symptoms can occur concomitantly with various diseases.
  • the term "improvement” refers to the prevention and delay of occurrence of a disease or condition, etc .; reduction of risk of occurrence of a disease or condition, etc .; improvement of a disease, condition or condition; deterioration of a disease, condition or condition Prevention and delay; maintenance of function, prevention of deterioration and delay etc. Therefore, the composition of one aspect of the present invention can be expected to prevent, suppress, alleviate, treat, etc. urination disorder in the individual using it by having a urination disorder improving action.
  • the drainage or storage symptoms as exemplified above may be associated with a disease or condition such as, for example, overactive bladder, prostatic hypertrophy, reduced bladder contraction, bladder outlet obstruction, and reduced urethral closure pressure.
  • a disease or condition such as, for example, overactive bladder, prostatic hypertrophy, reduced bladder contraction, bladder outlet obstruction, and reduced urethral closure pressure.
  • the urination disorder ameliorated by the composition of one embodiment of the present invention is, for example, excretory symptoms and urine accumulation symptoms as described above, and overactive bladder, prostate hypertrophy, bladder contraction reduction, bladder outlet obstruction, and urethral closure pressure reduction. And the like may be associated with a disease or condition such as
  • Overactive bladder is accompanied by a sense of urgency, which is a symptom of sudden, unbearable urgency. Overactive bladder may also be associated with one or more symptoms selected from the group consisting of pollakiuria, nocturia and urinary incontinence.
  • anticholine is used as the first choice drug.
  • Prostatic hyperplasia may be associated with increased flow resistance and / or impaired bladder blood flow due to lower urinary tract obstruction.
  • an alpha 1 blocker is used as the first-line drug.
  • Bladder contraction, bladder outlet obstruction, and urethral closure pressure reduction are urinary discharge disorders and are accompanied by symptoms such as urinary loss, urination loss, delayed urination, urinary retention, and residual urine.
  • urination disorder is one or more symptoms selected from the group consisting of pollakiuria, nocturia, urinary incontinence, residual urine feeling, urinary decline, urinary retention, urination delay, urinary retention.
  • May be Frequent urination is a condition in which the frequency of urination from getting up to bedtime increases. Usually, when the number of times of urination per day is 8 or more, it is diagnosed as frequent urination, but it is not limited to this.
  • Nocturia is a symptom of temporary rising for urination from bedtime to waking up, and usually it is diagnosed as nocturia if there is more than one urination, but it is not limited thereto.
  • Urinary incontinence refers to a condition in which urine leaks involuntarily or unconsciously. Urinary incontinence includes stress incontinence, urge incontinence, overflow incontinence, reflex incontinence, true incontinence.
  • the feeling of residual urine is a symptom accompanied by the sensation that urine remains in the bladder (residual urine) even after urination, and such sensation occurs regardless of the presence or absence of residual urine. Attenuation is a symptom in which the momentum of urination decreases and the urination time becomes long, and it is a symptom said to be poor in appearance.
  • Urinary line disruption is an abnormal urinary tract when there is an abnormality in the external urethral opening, which is the outlet of urine, and urination is interrupted during urination, and urinary line interruption is referred to as urinary line disruption.
  • Bladder calculus and clot happenss to block the outlet of the bladder. Delayed urination is a time-consuming task until urine begins to come out, and is seen when a foreign body is created below the bladder or inflammation occurs and the urethra narrows.
  • Urinary retention is a condition in which urine does not come out despite the accumulation of urine in the bladder, and it can be caused by hypertrophy of the prostate if the bladder becomes tight with intense urination.
  • Overactive bladder may be due to detrusor overactivity due to the lower urinary tract itself or to detrusor hyperreflexia due to the central nervous system.
  • the cause of frequent urination without urgency also includes congestion of the bladder, which is said to be one of the causes of chronic prostatitis.
  • the above symptoms may be urinalysis, prostate specific antigen (PSA) measurement, urine flow measurement, ultrasonography, computed tomography (CT) examination, magnetic resonance imaging (MRI) examination, urination cystography, urodynamic examination or these
  • the urination disorder improved by the composition of one embodiment of the present invention includes urge incontinence from overactive bladder, urination frequency during the day, urination frequency during the night, urgency, urination frequency from the prostatic hyperplasia, during the night It may be the frequency of urination, a sense of urgency, a feeling of residual urine, poor appearance, or a bladder contraction, bladder outlet obstruction, and a feeling of urinary retention or residual urine due to a reduction in urethral closure pressure.
  • Evaluation of the urination disorder ameliorating action is to perform continuous intravesical pressure measurement when predetermined doses of these extracts are intravenously administered for a predetermined period to lower urinary tract disorder model animals, and differences in bladder activity are continuously determined. It can do by measuring. In addition, it can be carried out by measuring the frequency of nocturia and the like when a predetermined amount of the composition of one embodiment of the present invention is orally administered to a used individual.
  • composition for improving urination disorder is a composition for ameliorating urination disorder, which comprises an extract of the abalone extract as an active ingredient.
  • Substances having a urination disorder ameliorating action are said to be able to improve the neurotransmission environment by improving the binding between the neurotransmitter and the receptor, which is generally related to the urination of the used individual applied.
  • the composition for improving urination disorder may be for improving the above-mentioned neurotransmission environment, but is not limited thereto.
  • the used individual includes animals, particularly mammals, and mammals include humans, dogs, cats, cattle, horses, etc. Among them, human is preferred.
  • the composition for ameliorating urination disorder can take the form of a composition for food or drink, a composition for medicine, etc. in which it is used alone or in itself. Therefore, one specific embodiment of the composition of the present invention is an oral or non-oral composition containing a composition for improving urination disorder which contains a berry extract as an active ingredient or containing a berry extract as an active ingredient.
  • the composition is an oral food / drink composition, a pharmaceutical composition, a quasi drug composition, a cosmetic composition, an animal feed composition, and the like.
  • composition for improving urination disorder may be orally or parenterally administered as described above, but in view of daily intake,
  • the composition for oral use is preferable, and the composition for food and drink or the composition for oral medicine is more preferable.
  • composition for food and drink is, for example, a functional food and drink which is a food and drink having certain functionality to a living body.
  • Functional food and drink include, for example, food and drink for specified health, functional indication food and drink, nutrition function food and drink, health function food and drink, special purpose food and drink, nutrition supplement food and drink, health support food and drink, supplement, beauty food, etc.
  • the food and drink for specific persons such as food and drink for infants, food and drink for pregnant women, food and drink for elderly people, and the like are included.
  • functional food and drink include health food and drink to which health claim (Health claim) based on the food standards of Codex (FAO / WHO Joint Food Standards Committee) is applied.
  • the oral pharmaceutical composition may take any oral pharmaceutical form as long as it can at least ameliorate urination disorder after application.
  • the composition for oral pharmaceutical use may contain a physiologically active substance having an action to improve urination disorder other than the extract only, as long as the object of the present invention can be achieved.
  • agents containing as an active ingredient include anticholinergics, ⁇ 1 inhibitors, adrenoceptor agonists (mirabegron, TAK259 etc.) which have been used as conventional vomiting disorder symptomatic treatments, pentosan polysulfate, sodium hyaluronate hydrochloride, flavoxate, sernitine porene
  • anticholinergics ⁇ 1 inhibitors
  • adrenoceptor agonists adrenoceptor agonists
  • pentosan polysulfate sodium hyaluronate hydrochloride
  • flavoxate flavoxate
  • an extract, a beta 3 receptor stimulant, etc. are mentioned, it is not limited to these.
  • the intake amount of the composition for improving urination disorder is not particularly limited, and may be appropriately set according to the degree of the urination improvement effect required for the individual used, the intake mode, etc.
  • a single dose orally ingested And based on the weight of the individual used it is 0.0001 to 1,000 mg / kg, preferably 0.001 to 600 mg / kg, and more preferably 0.1 to 60 mg / kg, per day as an extract of Gishigishi It is.
  • the anchovy extract when the nepozin content of the anchovy extract is 10 to 30 wt%, 0.001 to 600 mg / kg of the anchovy extract corresponds to a constructivegin dose of 0.0001 to 180 mg / kg, and the anchovy extract 0.1 ⁇ 60 mg / kg corresponds to a dose of 0.01 to 18 mg / kg of romancegin.
  • the frequency of intake of the composition for improving urination disorder is not particularly limited, but is, for example, 1 to 3 times a day, and can be increased or decreased appropriately according to the degree of urination disorder and the intake amount of the used individual.
  • the intake period of the composition for improving urination disorder is continuously for a fixed period, that is, 3 days or more, preferably 1 week or more, more preferably 2 weeks or more, still more preferably 1 month or more, for example 6 months or 1 year or more It is preferred to administer.
  • administration of the composition for improving urination disorder is preferably performed daily, it may not be administered daily as long as it is continuously administered for a period.
  • the daily intake of the composition according to one aspect of the present invention is not particularly limited, and is, for example, 0.1 to 60,000 mg, preferably 10 to 6,000 mg, based on the total amount of the sage extract.
  • the form of the composition for ameliorating urination disorder for oral use is not particularly limited, and can be any form.
  • the composition for ameliorating urination disorder for oral use may take the form of, for example, tablets, powders, granules, powders, capsules, pills, troches, solutions and the like.
  • tablets include sugar-coated tablets, coated tablets, and buccal agents
  • capsules include both hard capsules and soft capsules.
  • Granules also include coated granules.
  • solutions include suspensions, emulsions, syrups, elixirs and the like, and syrups also include dry syrup.
  • compositions for food and drink for example, a berry extract or a composition for improving urination disorder, bread, cookies, biscuits, barley for rice addition, cereals, udon, soba, pasta and other noodles, cheese, yogurt and the like Dairy products, jams, mayonnaise, miso, soy sauce and other soy products, tea, coffee, cocoa, soft drinks, fruit drinks and other non-alcoholic beverages, medicinal liquor, other alcoholic beverages, candies, chocolate and other snacks, It can be added to chewing gum, rice crackers, gluten, and other confections using soybeans as a raw material in the form of a general food and drink.
  • the composition for improving urination disorder may at least contain a berry extract, but it may be a combination of a berry extract and other components.
  • the other components are not particularly limited, but, for example, additives for food and drink or oral medicine can be used as other components.
  • various excipients, binders, lubricants, stabilizers, diluents, extenders, emulsifiers, colorants, perfumes, perfume oils, thickeners, brighteners and the like can be used as other components.
  • the content of the other components can be appropriately selected according to the form of the composition of one embodiment of the present invention, and the like, as long as the solution to the problems of the present invention is not hindered.
  • lactose glucose, sucrose, mannitol, potato starch, dextrin, corn starch, calcium carbonate, calcium phosphate, calcium sulfate, crystalline cellulose, licorice powder, gentian powder and the like
  • binder for example, starch, gum tragacanth, gelatin, syrup, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose and the like can be mentioned.
  • disintegrants examples include starch, agar, gelatin powder, sodium carboxymethylcellulose, calcium carboxymethylcellulose, microcrystalline cellulose, calcium carbonate, methylcellulose, ethylcellulose, carboxymethylcellulose and the like.
  • lubricant for example, talc, magnesium stearate and the like can be mentioned.
  • coloring agent what is permitted to be added to food-drinks, a pharmaceutical for oral use, etc. can be used, It does not specifically limit.
  • the method of using the composition for ameliorating urination disorder for oral use is not particularly limited.
  • the composition for ameliorating urination disorder may be taken orally by eating or drinking as it is, diluted with water or the like or diluted with water or the like. be able to.
  • the composition for improving urination disorder and another solid or liquid may be mixed and taken orally, depending on the preference of the individual used.
  • the composition for improving urination disorder is an orally disintegrating dosage form, it can be taken orally without water.
  • the composition for ameliorating urination for parenteral use can be produced by adding a pH adjuster, a buffer, a stabilizer, a solubilizer, and the like.
  • the composition for ameliorating urination disorder for parenteral use can be used, for example, in a form suitable for a pharmaceutical composition for parenteral use and a cosmetic composition, that is, as a pharmaceutical composition for parenteral use and a cosmetic composition.
  • a composition for improvement of dysuria for parenteral use may be used as it is or mixed with additives usually used for processing of pharmaceutical compositions for parenteral use and cosmetic compositions, lotions, emulsions, gels, It can be processed into various forms such as creams and ointments.
  • the parenteral pharmaceutical composition can be present in the form of a pharmaceutically acceptable salt form, wherein the extract of the abalone extract is dissolved in a water-soluble solvent.
  • Such pharmaceutically acceptable salt forms include those that are buffered at physiological pH in the form of physiologically acceptable water-soluble salts, such as sodium, potassium, magnesium, calcium and the like salts.
  • water-soluble solvents non-water-soluble solvents can be used, and examples of such non-water-soluble solvents include alcohols, ethanol, propylene glycol and the like.
  • compositions for parenteral use may contain preservatives, buffers, and the like as other components other than the extract of shiitake mushroom.
  • preservatives sodium bisulfite, sodium bisulfate, sodium thiosulfate, benzalkonium chloride, chlorobutanol, thimerosal, phenylmercuric acetate, phenylmercuric nitrate, methyl paraben, polyvinyl alcohol, phenylethyl alcohol, ammonia, dithiothreitol, Beta mercaptoethanol etc. are mentioned.
  • buffer sodium carbonate, sodium borate, sodium phosphate, sodium acetate, sodium bicarbonate and the like can be mentioned.
  • the dosage form of the pharmaceutical composition for parenteral use is not particularly limited, and examples thereof include injections (muscle, subcutaneous and intradermal), oral preparations, nasal preparations and the like.
  • the composition for improving urination disorder can be packed in a container to make a container-packed composition sealed.
  • the container is not particularly limited.
  • metal such as aluminum, paper, plastic such as PET or PTP, single layer or laminated film bag, retort pouch, vacuum pack, aluminum container, plastic container, bottle, can, etc.
  • Packaging containers In order to avoid deterioration over time, the composition for improving urination disorder is preferably packed and sealed in a container and then sterilized by pressurization and / or heating or the like.
  • the method of one aspect of the present invention is a method of ameliorating urination disorder, comprising the step of ameliorating the urination disorder of the individual by administering the composition of one aspect of the present invention to the individual.
  • the above items can be appropriately referred to for the administration method and the confirmation method for the improvement effect of the urination disorder of an individual.
  • various steps and operations can be added before, during, or after the above steps as long as the problems of the present invention can be solved.
  • Example 1 Method of measuring the components of the extract of moth extract.
  • the measurement wavelength was set to 225.0 nm, and it was measured by the calibration curve method as a peak having a retention time of about 11 to 12 minutes.
  • Example 2 Method of producing an extract of moth extract
  • 500 g of Gishigishi root was cut with a garden shredder ("GS-2010", RYOBI), followed by hot-air drying at 40 ° C for 24 hours to obtain 100 g of dried Gishigiri root.
  • the dried anchovy root was added in 1 L of ethanol, and it left still at room temperature for 8 hours, and the anchovy root crude extract was obtained.
  • the obtained fresh root extract of spinach was suction filtered using a diaphragm pump and a filtration bottle to obtain a rough root extract of spinach.
  • the resulting solid was added to 100 ml of a 0.1% (w / v) aqueous sodium hydrogen carbonate solution and stirred to obtain a suspension.
  • the resulting suspension was separated by centrifugation (7,500 rpm, 10 minutes) to obtain a supernatant and a precipitate.
  • the resulting precipitate is added to 200 ml of a 0.1% (w / v) aqueous solution of sodium hydroxide, stirred, and then separated by centrifugation (7,500 rpm, 10 minutes) to obtain a supernatant and a precipitate.
  • the extract of ethanol crude root extract extracted with ethanol is further treated with water, weak alkali, strong alkali and acid to obtain an extract of root extract containing nepogin etc. at high concentration. I got Thus, the extract of the present invention was obtained.
  • Example 3 An action to improve urination disorder by a berry extract (1)
  • Preparation of pelvic congestion and urination disorder rat model Sixteen Sprague-Dawley (SD) female rats (about 200 g) are undercut in the middle of the lower abdomen under 2% isoflurane inhalation anesthesia, and ligatures of both common iliac vein and uterine vein to pelvis He was congested and closed, and he was treated as a pelvic congestion group (disability treatment).
  • SD female rats about 200 g
  • eight SD female rats which were subjected to only an operation of removing both common iliac veins and uterine veins from surrounding tissues were used as a control group (sham treatment). It was used for the following experiment 3 weeks after the operation.
  • Intravenous administration experiment of gishigishi In 8 animals of pelvic congestion group and 8 animals of control group, insert a catheter for measuring intravesical pressure about 1 mm in diameter transurethrally into the bladder under 2% isoflurane inhalation anesthesia and insert a 3-way stopcock It was used as a saline injection passage into the bladder and an internal pressure measurement passage.
  • a venous indwelling needle was inserted into the femoral vein on one side, and it was used for administration of the extract of moth.
  • Continuous bladder pressure measurement refers to a test that measures the pressure in the bladder while injecting a certain amount of physiological saline from the urethra to confirm bladder function.
  • bladder contraction interval minutes
  • baseline Pressure cm H 2 O
  • maximum bladder contraction pressure cm H 2 O
  • the pelvic congestion group had a significantly shorter bladder contraction interval (voiding interval) and a frequent urination than the control group (Table 1, Figure 1, before administration).
  • the bladder contraction interval is extended in a concentration dependent manner, and for the 4 th group extract 1 mg / kg, the bladder contraction interval is It was prolonged to approximately twice compared to the pelvic congestion group in the first group before administration (Table 1, FIG. 1).
  • Example 4 An action to improve urination disorder by the extract of moth extract (2)] The following tests were conducted on subjects in order to prove that the extract of Muskworm has an effect of improving symptoms and phenomena due to dysuria.
  • hard capsules were prepared (hereinafter referred to as "Gishigishi extract tablets").
  • the subjects were obese adult male and female volunteers who were over 40 years old with metabolic syndrome, locomotive syndrome, or their risk, and 60 males and females over 20 years old with a waist width of 85 cm or more and women 90 cm or more.
  • a drug containing a capsule containing only dextrin without the berry extract powder was orally administered to the group without the berry extract intake under the same conditions as described above. The same diet was given to both groups.
  • the administration was once a day in the morning, and was administered daily (orally). At the start of administration, the first three weeks and the second six weeks later, the frequency of nocturia was checked by a questionnaire, and hematological examination and blood biochemistry examination were performed.
  • composition containing Nepogin etc.-containing moth extract has the effect of treating urination disorder, since it suppresses the number of urination at night.
  • composition according to one aspect of the present invention is a useful extract of moth extract, which is capable of improving dysuria on a used individual.

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Abstract

La présente invention a pour objet de fournir une composition pour l'amélioration de la dysurie, contenant, en plus d'une substance naturelle telle que la nobiletine qui représente une technique antérieure, un composant dérivé d'une substance naturelle qui est de façon similaire efficace contre la dysurie, qui est sûr à l'emploi, et qui peut être produit à partir de matières premières qui sont facilement disponibles en grandes quantités. L'objectif décrit ci-dessus est atteint à l'aide d'une composition pour l'amélioration de la dysurie contenant un extrait de Rumex japonicus en tant que principe actif.
PCT/JP2018/025478 2017-07-05 2018-07-05 Composition pour l'amélioration de la dysurie Ceased WO2019009354A1 (fr)

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JP2006347952A (ja) * 2005-06-16 2006-12-28 Yoshihiro Futamura リパーゼ活性化作用を呈するアントラキノン誘導体、それからなる抗肥満薬、食品製剤及び化粧品
JP2011522822A (ja) * 2008-06-06 2011-08-04 バイオノボ・インコーポレーテッド エストロゲン受容体β媒介性病状の治療のためのダイオウ（Ｒｈｅｕｍｐａｌｍａｔｕｍ）由来のアントラキノンおよび類似体
WO2012014524A1 (fr) * 2010-07-30 2012-02-02 株式会社エリナ Composition d'amélioration du métabolisme du sucre, et préparation pharmaceutique contenant ladite composition
JP2014079188A (ja) * 2012-10-16 2014-05-08 Kimio Sugaya 無菌性慢性前立腺炎非ヒトモデル動物、頻尿非ヒトモデル動物およびこれらを用いた被験物質の評価方法
JP2014079187A (ja) * 2012-10-16 2014-05-08 Kimio Sugaya 骨盤うっ血モデルラットおよびその作製方法
WO2016075960A1 (fr) * 2014-11-12 2016-05-19 株式会社沖縄リサーチセンター Composition médicinale pour prévenir ou améliorer la dysurie, antagoniste contre un récepteur associé à la dysurie et procédé pour prévenir ou améliorer la dysurie à l'aide de composition médicinale ou d'antagoniste
WO2017169311A1 (fr) * 2016-03-31 2017-10-05 株式会社沖縄リサーチセンター Procédé de production d'extrait riche en népodine de plante rumex, et extrait riche en népodine de plante rumex

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JP2002080366A (ja) * 2000-09-05 2002-03-19 Univ Kanazawa 夜間頻尿症の治療剤、夜間頻尿症の予防剤
JP2006347952A (ja) * 2005-06-16 2006-12-28 Yoshihiro Futamura リパーゼ活性化作用を呈するアントラキノン誘導体、それからなる抗肥満薬、食品製剤及び化粧品
JP2011522822A (ja) * 2008-06-06 2011-08-04 バイオノボ・インコーポレーテッド エストロゲン受容体β媒介性病状の治療のためのダイオウ（Ｒｈｅｕｍｐａｌｍａｔｕｍ）由来のアントラキノンおよび類似体
WO2012014524A1 (fr) * 2010-07-30 2012-02-02 株式会社エリナ Composition d'amélioration du métabolisme du sucre, et préparation pharmaceutique contenant ladite composition
JP2014079188A (ja) * 2012-10-16 2014-05-08 Kimio Sugaya 無菌性慢性前立腺炎非ヒトモデル動物、頻尿非ヒトモデル動物およびこれらを用いた被験物質の評価方法
JP2014079187A (ja) * 2012-10-16 2014-05-08 Kimio Sugaya 骨盤うっ血モデルラットおよびその作製方法
WO2016075960A1 (fr) * 2014-11-12 2016-05-19 株式会社沖縄リサーチセンター Composition médicinale pour prévenir ou améliorer la dysurie, antagoniste contre un récepteur associé à la dysurie et procédé pour prévenir ou améliorer la dysurie à l'aide de composition médicinale ou d'antagoniste
WO2017169311A1 (fr) * 2016-03-31 2017-10-05 株式会社沖縄リサーチセンター Procédé de production d'extrait riche en népodine de plante rumex, et extrait riche en népodine de plante rumex

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