KR20170036883A - A composition for preventing, treating and improving of voiding disorder comprising complex extracts - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating urinary disturbances and a functional health food for preventing or alleviating urinary disturbances, the pharmaceutical composition and the functional health food comprising as active ingredients, one or more extracts selected from the group consisting of a Piper Longum L. extract, Euryale ferox, Allium tuberosum, Cucurbita moschata, Poria cocos, Schisandra chinensis, Lindera strychnifolium, Cuscuta chinensis and Polygonum cuspidatum. A complex extract of the present invention, which is a natural extract, is harmless to the human body; increases the urination interval by simultaneously intervening in various mechanisms involved in urinary disturbances; reduces the detrusor pressure and increases the bladder volume; suppresses the contraction of detrusor muscles and induces the relaxation of detrusor muscles, and thus has an excellent effect on the prevention, treatment, or alleviation of various urinary disturbances.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing, treating and improving diabetes mellitus,

The present invention relates to a pharmaceutical composition for preventing or treating dysuria comprising an extract of Pepper and a complex extract of one or more extracts selected from the group consisting of guar, guacamole, mangin, phosphorus, omija, Compositions and health functional foods for preventing or ameliorating dysuria.

Urinary dysfunction refers to any urination that is out of normal urination. Urinary dysfunction may be present in any man or woman, including neurogenic bladder caused by neurological abnormalities, lower urinary tract symptoms due to non-neuronal causes, female urinary disease typified by urinary incontinence, and urinary incontinence (2003). Urinary disorders are reported to be prevalent in adults and increase with age, especially with a linear increase in men. In the lower urinary tract symptoms due to dysuria, it is known that the prevalence of dysuria is highest in both men and women. It is reported to be the most common symptom of dysuria and urinary symptoms.

Symptoms of various dysuria, such as overactive bladder, may limit the intake of beverages, experience annoyance that you often have to go to the toilet, be affected by interpersonal and social life, have hygiene problems, (2002), "The Effects of the Health-related Quality of Life on the Quality of Life", Journal of Health and Social Behavior, Vol.

Overactive bladder syndrome (OAB syndrome) is a complex syndrome in which the concept of a recent disease is established. Urinary tract infections and urinary incontinence (urinary incontinence) During this period, the bladder was abnormally shrunk frequently, causing frequent urination (more than 8 times a day), difficulty in urinating and urgency to go to the toilet, urination, Refers to the appearance of one or more symptoms of urgent urinary incontinence, or nighttime urinary symptoms that require urination at least once during nighttime sleep. Symptoms of irritable bladder usually result in involuntary contractions of the detrusor (bladder) leading to bladder hyperactivity.

Because the bladder is composed of smooth muscle and the voiding function is controlled by the nervous system, various voiding disorders such as overactive bladder can occur due to smooth muscle and nervous system abnormalities. The cause of irritable bladder is usually caused by neurogenic and spinal cord injuries, and outlet obstruction, which is characterized by men's enlargement of the prostate gland, weakening of the pelvic structure of the woman, local diseases of the urethra and bladder , But it is not clear yet whether the major cause of the disease is caused by the aging of the detrusor cells or the uncontrolled detrusor dysfunction (Kim Tae-hyung, Chungtaeji 28 (3), p143-149, 2003).

Although irritable bladder syndrome is not a process of aging, the probability of occurrence increases with age. Men and women are similar, but urge incontinence is more common in women. In Europe, a prevalence of overactive bladder is 16% in men over 40 years old, 17% in women, 42% in men over 75 years old and 31% in women over 75 years old. , And these statistics are similar in developed countries such as the United States and Japan (2011, Korea Urinary Incontinence Association, Overactive Bladder Handbook). The results of the health-related quality-of-life (HRQOL) survey of the patients showed that irritable bladder disease was associated with a decrease in quality of life due to social and psychological influences on basic physical activities, The effect of diabetes on the quality of life was greater than that of diabetes (Liberman JN, Hunt TL, Stewart WF, Wein A, Zhou Z, and Herzogar, Urology 2001; 57: 1044-50).

Currently, antimuscarinic agents are widely used as an initial standard therapy for irritable bladder. However, there is no report of controlled clinical trials to prove the efficacy yet, Due to its anticholinergic properties, it has been reported that 1-2 of 10 patients develop side effects such as dry mouth, constipation, blurred vision, and acute ejaculation. These side effects are reported to cause poor compliance with micturition dysfunction patients who need to control their water intake, and for this reason there has been a continuing need for the development of new alternative drugs for dysuria such as overactive bladder J Korean Continence Soc 2009; 13: 7-22).

Urinary incontinence is a sudden, involuntary urinary leak that occurs after a severe episode, and it is known that urinary incontinence is caused by specific sight, sound, contact with flowing water, and postural changes. Emptied urine is also called epigastric papillary, and the urge to urinate is a sudden onset of symptoms, and once the sensation of urination is detected, it means that you can not tolerate urination. In this case, if you do not see urine immediately, it can cause pain, and it is known that bladder can shrink freely and urge urine to squeeze urge incontinence. Urinary urination was defined as urination 4 to 6 times a day and urine more than 8 times per 24 hours, unlike normal adults with a urination volume of about 300cc per urine. However, in 2002, the International Incontinence Society The definition of frequency is defined as frequency. Urinary frequency is one of the typical symptoms of urinary dysfunction, which refers to abnormal urination symptoms, such as excessive water intake, detrusor activity and activity, decreased bladder volume, and sensitivity to bladder. Nighttime urine refers to nighttime sleeping and urination. Nighttime urine is classified into nighttime urine, which is relatively high compared to daily urination, and nighttime urine, which is not. In order to be defined as nocturia, sleep must be accompanied before and after urination. Patients with nighttime urination often fall asleep during sleep and can not easily fall asleep, which interferes with sleep, causing sleepiness and fatigue during the daytime and hindering daily life . In addition, the risk of falling or fracture increases in the elderly. Nighttime frequency is reported to be associated with several factors such as age, lifestyle, polyuria, nocturnal enuresis, bladder dysfunction, sleep disturbance, and psychological factors. Interstitial cystitis is also called bladder pain syndrome or chronic cystitis. There is no characteristic pathologic findings such as bacterial infection, and the exact cause has not yet been revealed. Although it is known that bladder epithelial cells are defective and the bladder mucosal wall between the urine and blood flow is damaged, inflammation in the bladder, vascular disturbance of the bladder, bladder mucosal injury and psychosomatic disorder can also be triggered factors. It occurs in both men and women, but about 90% occurs in women and occurs mainly in the mid-forties. Symptoms include abnormal sensory urgency and frequent urination. Especially when urine is cold, the symptoms are more severe and when urinating, there is little pain. Even at night, urine is seen on average four times more than once or twice, but there is little hematuria. At least 8 times a day, the average urine is 16 times. In normal people, the amount of urination at one time is more than 250 ml, but the amount of the patient is 75 ml. Three out of four patients become more aggravated by sexual intercourse, and the menstrual cycle, stress, and food also affect symptoms. Treatment with antidepressants, anesthesia followed by bladder drainage, bladder ablation, bladder augmentation, urinary conversion, or anticholinergic drugs, alpha adrenergic receptor blockers, antihistamines, steroids, silver nitrate, heparin However, there is a need for new drugs for the treatment of such urinary disorders.

Particularly, for the treatment of such urinary disorders, drugs developed for natural or natural substances that can be used without toxicity or risk to the human body are rarely found, and research and development using a synergistic effect of natural materials are not available at all . Under these circumstances, there is an urgent need to research and develop a therapeutic agent or a health functional food based on a complex extract for preventing or treating urinary disturbance by using natural products that can be easily used as a food or pharmaceutical material.

The present inventors have been studying natural products that can effectively prevent, treat and ameliorate various dysuria, and have found that they can be mixed with a petroleum extract, a guar, a mangin, a bamboo, an omija, a miso, The present invention has been accomplished by confirming that there is a remarkable effect in prevention, treatment and improvement of urinary disturbance without any harmful action to the human body when the extract of the present invention is used together with the extract.

Accordingly, an object of the present invention is to provide a method for preventing or treating dysuria, comprising an extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, manganese, omega, omega, Or a pharmaceutically acceptable salt thereof.

Also, the object of the present invention is to provide a method for preventing or treating dysuria, comprising an extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, And to provide a health functional food for prevention or improvement.

The present invention relates to a method for preventing or treating dysuria comprising an extract of Piper Longum L. and one or more extracts selected from the group consisting of proband, guar, A pharmaceutical composition is provided.

The present invention also relates to the above-mentioned extracts of Piper Longum L. and at least one extract selected from the group consisting of proband, guacamole, indigo, bamboo, omija, A pharmaceutical composition for preventing or treating dysuria, which is extracted with at least one extraction solvent selected from the group consisting of glycol, propylene glycol, methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, chloroform and dichloromethane . Preferably, the extraction solvent may be one or more extracting solvents selected from the group consisting of water, alcohol, ethyl acetate, n-hexane, chloroform and dichloromethane. More preferably, the extraction solvent may be water, an alcohol or a hydrated alcohol (aqueous alcohol solution). The alcohol may be methanol, ethanol or isopropanol. More preferably, the extraction solvent may be water or a functional ethanol (aqueous solution of ethanol).

The present invention also provides a pharmaceutical composition for preventing or treating dysuria, wherein the alcohol as the extraction solvent is an anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms. Preferably, the alcohol may be hydrous methanol (aqueous methanol solution) or hydrous ethanol.

More preferably, the alcohol may be hydrous ethanol (aqueous solution of ethanol).

Also, the present invention provides a pharmaceutical composition for preventing or treating dysuria, wherein the anhydrous or low-functional alcohol is 30 to 100% by volume of methanol or ethanol. Preferably, the functional lower alcohol may be an aqueous 30 to 100 volume / volume (vol / vol) ethanol solution. More preferably, the functional lower alcohol may be an aqueous solution of 30 to 95% by volume ethanol. More preferably, the functional lower alcohol may be a 95 vol% ethanol aqueous solution.

The present invention also relates to the use of the extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, omega, And a pharmaceutical composition for preventing or treating voiding dysfunction. The polar solvent-soluble extract may be an extract soluble in a solvent selected from water, methanol, butanol or a mixed solvent thereof, preferably in saturated n-butanol, and the non-polar solvent soluble extract may be dissolved in dichloromethane or ethyl acetate Lt; / RTI >

The present invention also relates to the use of the extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, omega, There is provided a pharmaceutical composition for preventing or treating dysuria.

The present invention also relates to a composition containing the extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, omega, The volume of which is increased.

In addition, the present invention provides a method for inhibiting detrusor contraction and inducing detrusor relaxation by extracting the Piper Longum L. extract and at least one extract selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, Or a pharmaceutically acceptable salt thereof.

In another aspect, the present invention, the pilbal (Piper Longum L.) extract, and gum, Ja, the South and, Poria cocos, Schizandra, ohyak, tosaja and call the one or more extracts selected from the group consisting of mousse or muscle Karin M ₃ muscarinic M < ₂ > receptors.

In addition, the present invention provides agonists of the pilbal (Piper Longum L.) extract, and gum, Ja, the South and, Poria cocos, Schizandra, ohyak, tosaja and No. ₃ are one or more kinds of extracts selected from the group consisting of muscle β receptor -adrenegic A pharmaceutical composition for preventing or treating voiding dysfunction.

In addition, the present invention provides a pharmaceutical composition for preventing or treating dysuria, wherein the dysuria is selected from the group consisting of an overactive bladder syndrome, urgency incontinence, urgency, urinary frequency, nocturia and interstitial cystitis.

The present invention also relates to a method for preventing or preventing dysuria comprising an extract of Piper Longum L. and at least one extract selected from the group consisting of probiotics, guacamole, manganese, omega, omega, And provides a health functional food for improvement.

In addition, the present invention provides a health functional food for preventing or improving dysuria, wherein the dysuria is selected from the group consisting of an overactive bladder syndrome, urge incontinence, urgency, urinary frequency, nocturia and interstitial cystitis.

The present invention also relates to the use of the extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, omega, And a health functional food for preventing or ameliorating dysuria.

It is also an object of the present invention to provide a Piper Longum L. extract for use in the prevention or treatment of dysuria, and at least one selected from the group consisting of probiotics, guacamole, manginam, omega, omega, And to provide a pharmaceutical composition comprising the extract as an active ingredient.

It is also an object of the present invention to provide a Piper Longum L. extract for use in preventing or ameliorating a dysuria, and a method for preventing or ameliorating dysuria by using at least one selected from the group consisting of Piper Longum L. extract, And to provide a composition comprising the extract as an active ingredient.

It is also an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of dysuria, which comprises a Piper Longum L. extract and a group consisting of a spermatozoa, a goat, a mangin, a bamboo, an omija, And to provide the use of at least one selected extract.

Also, the object of the present invention is to provide a method for preventing or treating dysuria, comprising an extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, Prophylactic or therapeutic agent for the prevention or treatment of dysuria by administering to a subject comprising a mammal.

The extract of the present invention and at least one extract selected from the group consisting of proband, guar, mangin, phosphorus, omija, omega, tosaja and janggang are not only harmless to human body but also have various mechanisms involved in dysuria It is effective to prevent, treat or ameliorate various voiding disorders because it can increase voiding interval, decrease urine pressure, increase bladder volume, inhibit detrusor contraction and induce relaxation of detrusor muscle. Do. Particularly, it is possible to prevent or treat various dysuria according to the synergistic effect of the combined extracts of at least one extract selected from the group consisting of probiotics used in combination with the extract of Liliaceae, Guju, Nam-In, Bomyeong, Omija, Or have a significant effect on improvement.

FIG. 1 is a graph showing the results of confirming the changes in the number of urination, the amount of urination, and the amount of urination caused by the treatment with the compound extract of Lilium and Omija.

The present invention relates to a method for preventing or treating dysuria comprising an extract of Piper Longum L. and one or more extracts selected from the group consisting of proband, guar, A pharmaceutical composition is provided.

The complex extract according to the present invention refers to an extract of a mixture of a petal extract and at least one extract selected from the group consisting of a probiotic, a guar, a southern, a bamboo, an omija, a miso, a tortoise and a callus root.

Preferably, the combined extracts of the petals and the probes, the combined extracts of the petals and the goats, the combined extracts of the petals and the male and female, the combined extracts of the petals and the petals, the combined extracts of the petals and the oats, Complex extract, or a combination extract of Lilium and Liliaceae.

In addition, the extract may be a combined extract of at least two kinds of extracts selected from the group consisting of Liliaceae extract and Seongin, Gujwa, Namhaein, Byeongryeong, Omija, Omega, Sorghum and Hojanggang.

The complex extract may be a complex extract obtained by firstly mixing at least one selected from the group consisting of the above-mentioned petals, probucol, guacamole, ginseng, bamboo, omija, And extracts of at least one member selected from the group consisting of bamboo shoots, omija, oak, algae, and carrageenan, respectively, and then mixing them.

The extract of the present invention and at least one extract selected from the group consisting of proband, guaja, mangin, phosphorus, omija, omega, tosaja and phyllotaxis are not only harmless to the human body but also participating in various mechanisms involved in dysuria This may increase the voiding interval, decrease the voiding pressure, increase the volume of the bladder, inhibit the contraction of the detrusor, and induce relaxation of the detrusor. The preventive, curative and ameliorative effects of the compound extract of the present invention are not only the bladder but also the muscarinic M ₃ receptor or muscarinic M ₂ receptor involved in the contraction and relaxation of the bladder in the nervous system of the spinal cord and spinal cord upper part (enteric nervous system) And activating β ₃ -adrenergic receptor receptors. In particular, the synergistic effect of the combination of natural products is more remarkable in prevention, treatment and improvement of micturition disorder .

The term " Piper Longum L. " of the present invention includes any stem, leaf, roots, fruit or seed which can be used without limitation for cultivation, harvest or market and exhibits an effect of preventing, And may be preferably Piperis Longi Fructus.

The "Euryale ferox" of the present invention can include any stem, leaf, root, fruit or seed of a proband, which can be used without limitation for cultivation, harvesting or marketing, and can be used to prevent, treat or ameliorate dysuria , Preferably the seed of the proband (Euryales Semen).

The term " Allium tuberosum " of the present invention may include any stem, leaf, root, fruit or seed which can be cultivated, harvested, or marketed without limitation and exhibits an effect of preventing, treating or improving dysuria Preferably, a seed of Allii Tuberosi Semen.

The term " Cucurbita moschata " of the present invention includes all stem, leaf, root, fruit and seed of a male and female which can be used without limitation for cultivation, collection or sale and exhibit the prevention, Preferably, a seed of a person and a person (Cucurbitae Semen).

The "Poria cocos" of the present invention can be cultivated, harvested, or marketed without limitation, and any part of the cells can be used so long as they exhibit the preventive, therapeutic or ameliorative effect of dysuria.

The term " Schisandra chinensis " of the present invention can include any stem, leaf, root, fruit or seed of an omija that can be used without limitation for cultivation, collection or sale, and exhibits an effect of preventing, Preferably, Schizandrae Fructus. ≪ / RTI >

The term " Lindera strychnifolium " may include any stem, leaf, roots, fruit or seed of an ophthalmic solution, which may be cultivated, harvested or marketed without limitation and exhibits the preventive, Preferably Lindauer Radix. ≪ RTI ID = 0.0 >

The term " Cuscuta chinensis " of the present invention can include any stem, leaf, root, fruit or seed which can be cultivated, harvested, or marketed without limitation, and exhibits an effect of preventing, treating or improving dysuria And preferably a seed of Cuscutae Semen.

The "Polygonum cuspidatum" of the present invention includes all the stem, leaf, roots, fruit and seeds of a root, which can be cultivated, harvested, or marketed without restriction and exhibit the preventive, And may be preferably a root, stem (Polygoni Cuspitati Rhizoma et Radix).

Each of the extracts of the present invention may be extracted with a common extraction solvent, for example, water, water, and the like; Anhydrous or hydroalcohol; Polyhydric alcohols such as glycerin, butylene glycol and propylene glycol; Hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether and dichloromethane; Or mixtures thereof may be used, but are not limited thereto. The extracts of the present invention are preferably selected from the group consisting of water, alcohol, glycerin, butylene glycol, propylene glycol, methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, chloroform and dichloromethane Or may be extracted with the above-mentioned extraction solvent. Preferably, the extraction solvent may be one or more extracting solvents selected from the group consisting of water, alcohol, ethyl acetate, n-hexane, chloroform and dichloromethane. More preferably, the extraction solvent may be water, alcohol or hydrated alcohol. The alcohol may be methanol, ethanol or isopropanol. Even more preferably, the extraction solvent may be water or a functional ethanol.

Preferably, the extracts of Lilium, Rhizoma, Guadia, Namhae, Bomyeong, Omija, Ojak, Sorghum and Rhizoma of the present invention may be extracted with an anhydrous or a lower alcohol having 1 to 4 carbon atoms as an extraction solvent, The anhydrous or hydrated alcohol having 1 to 4 carbon atoms may be 10 to 100% by volume, preferably 30 to 100% by volume, and more preferably 70 to 100% by volume of methanol or ethanol. Preferably, the extraction solvent may be water or 30 to 95% by volume ethanol. Hereinafter, what is referred to as '% alcohol' is used in the same sense as 'volume% alcohol'.

For example, the extracts are preferably, but not necessarily, prepared by a manufacturing method comprising the following steps.

(1) a step of drying and then removing at least one selected from the group consisting of a petal, a proband, a goat, a southern person, a bamboo shoot, an omija, a miso, a sorghum and a callus root;

(2) extracting the extracted natural product by adding an extracting solvent to the natural product;

(3) cooling and extracting the extract;

(4) concentrating the filtered extract;

The extract used in the step (1) may be cultivated, harvested, or marketed without limitation, and the step (1) is preferably carried out by shade drying in a shady place.

The extraction in step (2) may be performed by an extraction method such as stirring extraction, refluxing cooling extract, cold extraction, ultrasonic extraction, supercritical extraction and the like, but is not limited thereto. The extraction temperature is preferably 50 to 120 ° C, more preferably 80 to 100 ° C. The extraction time is preferably 1 to 20 hours, more preferably 2 to 5 hours. Further, the number of extraction times may be 1 to 5, and more preferably 2 or 3 times. The extraction in step (2) may be carried out by adding an extraction solvent in an amount of 1 to 20 times the volume of the natural product.

The filtration in the step (3) may be performed at 100 to 500 mesh, but 300 mesh is preferably used.

The concentration in the step (4) may be carried out at 10 to 100 ° C, preferably at 50 to 80 ° C, and it is preferable to use a vacuum decompression condenser or a vacuum rotary evaporator.

Further, in addition to the above-mentioned production method, the method may further include a drying step of step (5), and the drying may be performed using a vacuum drying method, a vacuum drying method, a boiling drying method, a spray drying method, or a freeze drying method.

In addition, the extracts of the present invention may contain fractions of the above extracts, such as the extracts of Pepper, Sauter, Guza, Nam-In, Bokryeong, Omija, Ojak, Sorghum and Sorghum. The fraction extract of the above extracts can be obtained by extracting the extract obtained by using an anhydrous or hydro-lower alcohol having 1 to 4 carbon atoms as an extraction solvent, using a mixed solvent of anhydrous or hydroalcohol having 1 to 4 carbon atoms or acetonitrile and water as a mobile phase, ≪ RTI ID = 0.0 > and / or < / RTI >

The present invention also relates to the use of the extract of Piper Longum L. and one or more extracts selected from the group consisting of probiotics, guacamole, mangin, phosphorus, omija, omega, And a pharmaceutical composition for preventing or treating voiding dysfunction. The polar solvent-soluble extract may be an extract soluble in a solvent selected from water, methanol, butanol or a mixed solvent thereof, preferably saturated n-butanol, and the non-polar solvent-soluble extract may be extracted with dichloromethane or ethyl acetate Lt; / RTI >

The extract of Piper Longum L. of the present invention and one or more extracts selected from the group consisting of proband, guar, mangin, phosphorus, omija, omega, It may be involved in the cAMP signal transduction pathway of β ₃ -adrenegic receptor as well as the carin mechanism, so that it can target a complex mechanism involved in dysuria, thereby improving various dysuria.

Thus, the combined extract of the present invention may be to reduce the urination pressure and increase the volume of the bladder. In addition, the complex extract of the present invention may induce detrusor contraction inhibition and detrusor relaxation.

The complex extract of the present invention may also inhibit muscarinic M ₃ or muscarinic M ₂ receptors and may be an agent of the β ₃ -adrenegic receptor.

The M ₃ / M ₂ receptor is a parasympathetic neural receptor that is distributed in the eye, urinary tract, gastrointestinal tract, and cardiovascular system, and the related diseases or symptoms include chronic obstructive pulmonary disease, chronic bronchitis, asthma, adult / acute respiratory distress syndrome, , Bronchial reactivity, pulmonary fibrosis, pulmonary or allergic rhinitis, irritable bowel syndrome, convulsive colitis, gastroduodenal ulcer, gastrointestinal seizures or hypermobility, diverticulitis, convulsions of the gastrointestinal smooth muscle; Dysuria including urinary incontinence, neurogenic enuresis, neurogenic bladder, enuresis, mental-physical bladder, incontinence associated with bladder spasms or chronic cystitis, irritable bladder syndrome, feeding or urinary incontinence.

The β ₃ -adrenegic receptor is distributed in the bladder, brown adipose, and white adipocytes, and the related diseases or symptoms include overweight, obesity, impaired glucose tolerance, type 1 diabetes, type 2 diabetes mellitus, Bladder outlet obstruction, bladder outlet obstruction, irritable bladder syndrome, urination or urination.

Therefore, the " dysuria of the present invention " may include various disorders outside the normal urinary pattern associated with urination, such as low activity of detrusor muscle such as abnormal contraction or relaxation of detrusor, detrusor instability, sensory urgency This can be a disability caused by In particular, the urinary disorder is preferably a symptom of storage, including urinary frequency, nocturia, urgency, urinary incontinence, enuresis; Urinary symptoms including urinary symptoms, urinary incontinence, urinary frequency, urinary frequency; Urinary incontinence, urinary incontinence, urinary incontinence, intermittent urination, interstitial cystitis, interstitial cystitis, interstitial cystitis, urinary retention, urinary symptoms and interstitial cystitis, Lt; / RTI >

In addition, the pharmaceutical composition of the present invention can be used alone, or in combination with methods using surgery, hormone therapy, drug therapy, and biological response modifiers for prevention, treatment, or improvement of dysuria.

The pharmaceutical composition of the present invention can be formulated by adding a pharmaceutically acceptable carrier. For formulation, refer to Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA. The pharmaceutically acceptable carrier means those conventionally used in the manufacture of a pharmaceutical composition for a person skilled in the art to which the present invention belongs. For example, there may be mentioned lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, Water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Pharmaceutically acceptable carriers also include diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like. Such solid preparations can be prepared by incorporating into the pharmaceutical composition of the present invention at least one or more excipients such as starch, calcium carbonate, sucrose, Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. Various excipients such as wetting agents, sweeteners, fragrances and preservatives may be included in addition to water and liquid paraffin, which are commonly used simple diluents. have.

Examples which may be mentioned for skin administration are suitable for the production of dusting powders, emulsions, suspensions, oils, sprays, ointments, ointments, creams, pastes, gels, foams or solutions, and may be formulated as transdermal therapeutics (TTS) ) And / or excipients. The topical pharmaceutical preparations of the present invention may be semi-solid formulations, in particular ointments (ointments, suspension ointments), creams, gels or pastes. Lactic alcohol, cetyl alcohol, stearyl alcohol, fatty acids such as palmitic acid or stearic acid, liquid or solid paraffin or ozokerite, liquid or solid waxes, for example, For example, isopropyl myristate, natural or partially synthetic fats such as coconut fatty acid triglycerides, hydrogenated oils such as hydrogenated peanut or castor oil, or fatty acid partial esters of glycerol, such as glycerol monostearate or glycerol There is distearate. Suitable emulsifiers include surfactants, such as nonionic surfactants, such as polyalcohols or fatty acid esters of ethylene oxide adducts thereof, such as polyglycerol fatty acid esters or polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters such as Sorbitan oleate and / or sorbitan isostearate, isostearate, sterol or polyoxyethylene fatty alcohol ethers or fatty acid esters, anionic surfactants, for example alkali metal salts of fatty alcohol sulfates, such as sodium lauryl Sodium cetyl sulfate or sodium stearyl sulfate, which are commonly used in the presence of the fatty alcohols described above, for example cetyl alcohol or stearyl alcohol. Among them, it is possible to add an agent for preventing the drying of the cream, for example, a polyalcohol such as glycerol, sorbitol, propylene glycol and / or polyethylene glycol to the aqueous phase or to add a preservative, perfume or the like to the aqueous phase.

However, the present invention is not limited to the above-listed pharmaceutically acceptable carriers and the like, and these are merely illustrative.

The amount of the complex extract to be contained in the pharmaceutical composition varies depending on the condition and body weight of the patient, the severity of the disease, the drug form, the administration route and the period, but may be appropriately selected depending on the case. In the present invention, the term " administration " means introducing a composition for preventing or treating voiding dysfunction of the present invention to a patient by any appropriate method, and the administration route of the composition for preventing or treating voiding dysfunction of the present invention As long as it can be administered via any conventional route. For example, the wilt extract may be administered at a dose of 1 to 2400 mg / day, preferably 10 to 1000 mg / day, based on 60 kg adult, and the application may be administered once or several times a day It can also be applied. In addition, the pharmaceutical composition may contain 0.0001 to 50% by weight of the complex extract, based on the total weight of the composition. The pharmaceutical composition may be applied to mammals such as humans by various routes, for example, transdermal, oral, intravenous, intramuscular, or subcutaneous injection.

The present invention also relates to a method for preventing or preventing dysuria comprising an extract of Piper Longum L. and at least one extract selected from the group consisting of probiotics, guacamole, manganese, omega, omega, And provides a health functional food for improvement.

The health functional foods of the present invention include those defined in the Korean Health Function Act (FUNCTIONAL HEALTH FOODS ACT) enacted on August 26, 2002. Specifically, the term "health functional food" includes foods prepared or processed in the form of tablets, capsules, powders, granules, liquids, or rings using raw materials or ingredients having useful functions in the human body.

The voiding disorder may include various disorders outside the normal voiding pattern associated with voiding, and may be a disorder caused by low activity of detrusor muscle, instability of detrusor, sensory urgency, etc., such as abnormal contraction or relaxation of detrusor muscle And preferably at least one selected from the group consisting of irritable bladder syndrome, urge incontinence, urgency, urinary frequency, nocturia and interstitial cystitis.

The health functional food may contain flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts, , Protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like, as well as pulp for the production of natural fruit juice and fruit juice drinks and vegetable drinks ≪ / RTI > These components may be used independently or in combination.

The health functional food may be any one of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcoholic beverage, .

The above health functional food may further contain food additives, and the suitability of such food additives as "food additives" shall be determined by the General Food and Drug Administration, Shall be determined according to the relevant standards and standards.

Examples of the substances found in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, persimmon extracts, licorice extracts, crystalline celluloses, high- , A sodium L-glutamate preparation, a noodle-added alkaline agent, a preservative preparation, a tar coloring agent, and the like.

In the process for producing the health functional food of the present invention, the present extract of the present invention, which is added to foods containing beverages, can be appropriately added or decreased as necessary, and preferably 1 to 15 wt% %. ≪ / RTI >

The numerical values set forth herein should be construed to cover equivalent ranges unless otherwise indicated.

Hereinafter, preferred examples, examples and preparation examples of the present invention are presented for the purpose of facilitating understanding of the present invention. However, the following Preparation Examples, Examples and Preparation Examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the Production Examples, Examples and Preparation Examples. The natural products for the preparation of the extracts in the following preparations were purchased from UYONG Pharmaceutical Co., Ltd., Kyeongdong market (Wonsan-ro 147, Dongdaemun-gu, Seoul).

Production Example 1 . Petal  The extract and Fraction  Produce

Manufacturing example  1.1. Petal  Preparation of water extract

1 L of water was added to 100 g of sham and the mixture was refluxed for 3 hours and 30 minutes in a constant-temperature water bath (Hyundai Scientific, B-90). The extract thus obtained was filtered under reduced pressure using a filter paper, and the filtrate was concentrated under reduced pressure at 50-60 ° C. From this, 9.6 ± 0.1 g of a volumetric excretion extract (volumetric water extract) of 87.1% solids was obtained.

Manufacturing example  1.2. Petal  30 volume%  Preparation of ethanol aqueous solution extract

To prepare a 30 vol.% Ethanol aqueous solution extract, 6.0 L of a 30 vol.% Ethanol aqueous solution was added to 1 kg of shrunken volumetric flour and the mixture was heated at 80-90 DEG C for 3 hours and 30 minutes in a constant temperature water bath (Hyundai Scientific, B-90) . The filtrate was concentrated by evaporation using a vacuum rotary evaporator (EYELA, N-1100) under the condition of 50-60 ° C, and dried in a vacuum dryer (JEI0 Tech, OV-12) for 12 hours And dried to obtain a 30 vol% ethanol aqueous solution extract.

Manufacturing example  1.3. Petal  Preparation of water extract

Five grams of each shade of the volumetric flour was refluxed for 3 hours in a constant temperature water bath (Hyundai Scientific, B-90) using 100 mL of purified water. The filtrate was concentrated by evaporation using a vacuum rotary evaporator (EYELA, N-1100) at 50-60 ° C and dried over a period of 12 hours using a vacuum drier (JEIO Tech, OV-12) To obtain 0.76 g of a wilted water extract, and the results are shown in Table 1 below.

Manufacturing example  1.4. Petal Organic solvent  Preparation of extract

The extraction solvent was changed to ethanol, 95 vol.% Aqueous ethanol solution, methanol and ethyl acetate instead of water, and an extract was prepared in the same manner as in Preparation Example 1.2. The extraction was carried out in the same manner as in Preparation Example 1.2, except that dichloromethane, chloroform, and hexane were used as the extraction solvent and the solvent was extracted from the constant temperature water bath (Hyundai Scientific, B-90) at 60-70 ° C . The extract obtained was 0.21 g to 0.81 g, which is specifically shown in Table 1.

[Table 1]

Manufacturing example  1.5. Petal  Preparation of Extracts by Ethanol Aqueous Solution Concentration

Extraction was carried out in the same manner as in Preparation Example 1.2 except that the extraction solvent was changed to 30% by volume of ethanol, 50% by volume, 70% by volume and 95% by volume of ethanol aqueous solution. The extract obtained was 0.61 g to 0.86 g, which is specifically shown in Table 2.

[Table 2]

Manufacturing example  1.6. Petal 95 vol%  Aqueous ethanol extract Organic solvent Fraction  Produce

One kilogram of the shabby volumetric flour was subjected to reflux extraction in a constant temperature water bath (JISICO, J-BAL) for 3 hours and 30 minutes using about 10 L of a 95 vol% aqueous ethanol solution. The filtrate was concentrated by evaporation using a vacuum rotary evaporator (EYELA, N-1100) at 50-60 ° C and dried over a period of 12 hours using a vacuum drier (JEIO Tech, OV-12) To obtain 82.99 g of an aqueous 95 vol.% Ethanol aqueous solution extract. The above aqueous solution of 95% by volume of ethanol fraction was suspended in 1.5 L of distilled water, and 1.2 to 1.5 L of an organic solvent was added thereto. The organic solvent was separated and the organic solvent was removed and concentrated under reduced pressure. . The organic solvent fraction (56.13 g to 2.2 g) and the fraction of the water layer except for the organic solvent layer were prepared in the order of dichloromethane, ethyl acetate and n-butanol saturated with water, and the results are shown in Table 3 below.

[Table 3]

Manufacturing example  2. Preparation of extracts by concentration of aqueous solution of Omija ethanol

Manufacturing example  2.1. Preparation of aqueous solution of omija ethanol

To prepare an extract of Omiza ethanol aqueous solution concentration, each of 80 g of dried Omiza fruit was added with 30 vol%, 50 vol%, and 95 vol% ethanol aqueous solution of 800 mL of the corresponding volume of ethanol, Science, B-90) for 3 hours and 30 minutes. The filtrate was concentrated by evaporation using a vacuum rotary evaporator (EYELA, N-1100) under the condition of 50-60 ° C, and dried in a vacuum dryer (JEIO Tech, OV-12) for 12 hours And dried to prepare an aqueous solution of Omija ethanol. The extracts obtained were 42.25 g to 50.47 g, which are shown in Table 4 in detail.

[Table 4]

Manufacturing example  2.2. Schisandra 50% ethanol  Preparation of aqueous solution extract

To prepare an aqueous 50 vol.% Ethanol solution of Omija, 900 mL of 50 vol% ethanol aqueous solution was added to 100.1 g of dried Omiza fruit, and the mixture was refluxed for 6 hours in a constant temperature water bath (HS-SWB_D_6) at 80-85 ° C. The filtrate was concentrated by evaporation using a vacuum rotary evaporator (EYELA, N-1100) under the condition of 50-60 ° C, and dried in a vacuum dryer (JEIO Tech, OV-12) for 12 hours And dried to obtain 40.9 g of an aqueous 50 vol.% Ethanol aqueous solution of Omija.

Manufacturing example  However, Men and women , Byeongryeong, Omiza, Broken egg , Soil and Hojo Chang  Preparation of extract

Similarly to Preparation Example 2, aqueous ethanol aqueous solution extracts were prepared for each of the probes, guacamole, mangin, phosphorus, erythritol, erythritol and talc.

Manufacturing example  4. Petal  And Omija complex extract

The 30% ethanol aqueous solution extract prepared in Preparation Example 1.2 and the 50% ethanol aqueous solution extract prepared in Preparation Example 2.2 were mixed at a weight ratio of 1: 1, 3: 1 and 1: 3, respectively, .

Manufacturing example  5. Petal  Extracts, and probes, Men and women , Byeongryeong, Omiza, Broken egg , Soil and Hojo Chang  Preparation of complex extracts of extracts selected from extracts

Each of the combined extracts was prepared by separately blending extracts selected from the group consisting of Wax extract, Seongin, Guju, Nam-In, Bok-rye, Omija,

Example  One. SHR  Through non-anesthesia frequency assessment model Petal  And Omija complex extract

1.1 Experimental animals

12 week old male SHR was purchased from SLC (Japan). Day and night were adjusted to 12-hour cycles, and food and water were freely available. Experiments were conducted to measure the frequency of urination after administering a mixture of the solvent and the preparation of Example 4 to the 18-week-old SHR with the compound extract of Lilium and Omija.

10.2 Petal  And Omija Complex Extract

On the same day, the solvent was administered to the same SHR, and on the second day, the combined extract (30 vol.% Ethanol aqueous solution and 50 vol.% Ethanol aqueous solution of Schizandra chinensis extract 1: 1, 3: 1 and 1: 3) was administered at a dose of 300 mg / kg, and the volume of administration for two days was equal to kg / 10 ml. At this time, the solvent administered on the first day was DMSO / 10% Cremophor EL = 1: 9, vol / vol.

The results of the SHR administration of the solvent were used as the control group of the urination frequency index, and the SHR to which the experimental drug was administered was used as the experimental group. The SHR with the solvent and the experimental drug was immediately placed in the metabolic cage and the isometric transducer (Harvard apparatus) and MP150 (BIOPAC systems model no. MP150CE) were maintained for 16 hours (PM 5 to AM 9) The number of urination was measured. Paired t-test was used to compare the data of the number of urination for 16 hours after the administration of the drug (the first day) and the experimental drug (the second day).

The results are shown in Table 5 and FIG.

[Table 5]

As shown in Table 5 and FIG. 1, all of the manufactured complex extracts showed a tendency to decrease in the number of urination, which is a variable related to frequency of urination, in the overactive bladder compared to the solvent control, and a statistically significant improvement Respectively. In particular, the combined extract prepared by mixing 30 vol.% Ethanol aqueous solution and 50 vol.% Ethanol aqueous solution at a weight ratio of 3: 1 showed the most excellent improvement effect compared with the combined extract of other blending ratio for the irritable bladder.

Compared with the single extract of the present invention, the compound extract of Pemphil and Omija according to the present invention showed remarkable prevention, treatment and improvement of the dysuria.

Formulation example  1. Manufacture of medicines

1.1. Sanje  Produce

100 mg of Lilac and Omija complex extract

Lactose 100mg

Talc 10mg

The above components are mixed and filled in airtight bags to prepare powders.

1.2. Manufacture of tablets

100 mg of Lilac and Omija complex extract

Corn starch 100 mg

Lactose 100mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

1.3. Preparation of capsules

100 mg of Lilac and Omija complex extract

Corn starch 100 mg

Lactose 100mg

Magnesium stearate 2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

1.4. Injection preparation

100 mg of Lilac and Omija complex extract

Sterile sterilized water for injection

pH adjuster

(2 ml) per 1 ampoule in accordance with the usual injection method.

1.5. Liquid  Produce

100 mg of Lilac and Omija complex extract

Sugar 20g

20g per isomer

Lemon incense quantity

Purified water was added to make a total of 1,00 ml. The above components are mixed according to a usual method for producing a liquid agent, and then filled in a brown bottle and sterilized to prepare a liquid agent.

Formulation example  2. Manufacture of health functional foods

100 mg of Lilac and Omija complex extract

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

24.8 mg of magnesium chloride

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above components may be mixed And then used in the manufacture of a health functional food composition (for example, a nutritious candy, etc.) according to a conventional method.

Formulation example  3. Preparation of Health Functional Drink

100 mg of Lilac and Omija complex extract

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health functional beverage manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the resulting solution was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, It is used in the manufacture of the health functional beverage composition of the invention.

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (14)

Piper Longum L. extract and a pharmaceutical composition for preventing or treating dysuria comprising as an active ingredient at least one extract selected from the group consisting of probiotics, guar, mangin, phosphorus, omija, omega, Composition Wherein the extract is at least one selected from the group consisting of water, alcohol, glycerin, butylene glycol, propylene glycol, methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, chloroform and dichloromethane Wherein the composition is extracted with an extraction solvent. The pharmaceutical composition according to claim 2, wherein the alcohol is an anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms. 4. The pharmaceutical composition according to claim 3, wherein the anhydrous or low-boiling alcohol is methanol or ethanol in an amount of 30 to 100% by volume. The pharmaceutical composition for preventing or treating dysuria according to claim 1, wherein the combined extract increases the voiding interval. The pharmaceutical composition for preventing or treating dysuria according to claim 1, wherein the combined extract reduces the urine pressure and increases the volume of the bladder. The pharmaceutical composition for preventing or treating dysuria according to claim 1, wherein the complex extract inhibits detrusor contraction and induces detrusor relaxation. The pharmaceutical composition for preventing or treating dysuria according to claim 1, wherein the combined extract inhibits muscarinic M ₃ or muscarinic M ₂ receptor. The pharmaceutical composition for preventing or treating dysuria according to claim 1, wherein the combined extract is an agonist of? _3- adrenergic receptor. The pharmaceutical composition for preventing or treating dysuria according to claim 1, wherein the dysuria is at least one selected from the group consisting of an overactive bladder syndrome, urgent urinary incontinence, urgency, urinary frequency, nocturia and interstitial cystitis. The pharmaceutical composition according to claim 1, wherein the extract is a compound extract of Lilium and Omija, for the prevention or treatment of dysuria. Piper Longum L. extract, and a health function for preventing or improving urinary problems comprising at least one extract selected from the group consisting of probiotics, guinea pigs, mangin, phosphorus, omija, omega, food. 13. The health functional food for preventing or improving dysuria according to claim 12, wherein the dysuria is at least one selected from the group consisting of an overactive bladder syndrome, urgent urinary incontinence, urgency, urinary frequency, nocturia and interstitial cystitis. 13. The health functional food for preventing or improving dysuria according to claim 12, wherein the extract is a compound extract of Lilium and Omija.

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