JP2016155825A - Uricosuric composition, and food/drink using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a high-safety composition which is derived from a natural material, has no possibility of onset of Xanthinuria, and has an effect of reducing a uric acid value in human blood, and a food/drink having a composition for reducing a uric acid value in blood for prevention or treatment as an active ingredient.SOLUTION: There is provided a composition having an effect of reducing a uric acid value in human blood which is created by mixing a flat lemon lactic acid fermented product and a papaya lactic acid fermented product which contain a component derived from flat lemon (Citrus depressa) being a specialty from Okinawa and papaya, and flat lemon peel extract, and there is also provided a food/drink having a composition for reducing a uric acid value in blood for prevention or treatment as active ingredient.SELECTED DRAWING: None

Description

  The present invention relates to a uric acid excretion-promoting composition that is derived from Okinawa's special product, seeker and papaya, and that can promote uric acid excretion in urine, and food and drink with such pharmacological effects.

  In the body, purine bodies taken from food are broken down by the liver, producing almost a certain amount of uric acid every day. This uric acid is dissolved and circulated in body fluids such as blood, and almost the same amount as the production amount is mainly filtered from the kidneys into the urine and excreted. However, if the balance between uric acid production and excretion is lost due to some cause (for example, eating habits, alcohol consumption, stress, decreased kidney function, effects of drugs, genetic factors, etc.), the amount of uric acid in the body increases too much. May cause uricemia. By the way, the uric acid concentration in blood (serum uric acid level) is generally controlled within the range of 3.8 to 7.0 mg / dL for men and 2.4 to 5.8 mg / dL for women. If the value exceeds 7.0 mg / dL, the possibility of developing hyperuricemia is considered high.

  Hyperuricemia itself has no symptoms, but leaving it alone can cause various diseases including gout. That is, when the concentration of uric acid in the blood rises and exceeds the saturation concentration, uric acid that has become insoluble forms a salt with sodium to form crystals. If the concentration of uric acid continues to be high, these urate crystals will be deposited in various parts of the body.For example, if urate is deposited in the joints to cause gout, or crystallizes in the kidney, the urinary tract It can cause stones and kidney damage. Hyperuricemia is also said to cause ischemic heart diseases such as myocardial infarction.

  Currently, drugs that lower uric acid levels include drugs that promote excretion of uric acid, such as benzbromarone, and drugs that inhibit uric acid synthesis, such as allopurinol, and are prescribed according to the type of hyperuricemia in patients. Yes. These drugs currently prescribed are extremely excellent as a control agent for uric acid level, and the serum uric acid level can be returned to normal by taking the drug. However, since hyperuricemia itself is a very difficult disease to cure, if you stop taking the medicine, it will return to the state of hyperuricemia again. For this reason, in order to fundamentally treat hyperuricemia, it is necessary to continue taking the medicine patiently for a long time.

  The above-mentioned uric acid excretion enhancer increases the ability to excrete uric acid from the kidney by suppressing physiological reabsorption of uric acid in the tubules, and lowers the serum uric acid level. However, it is always necessary to pay attention to the development of urinary calculus during use, and side effects include gastrointestinal disorders, headache, and lightheadedness. Furthermore, it is said that severe liver damage occurs when administered to idiosyncratic patients.

  Moreover, as a uric acid production inhibitor, allopurinol has been introduced to gout treatment and is widely used. This allopurinol inhibits xanthine oxidase, which acts at the final stage of the purine metabolic pathway, and reduces the amount of uric acid excreted in urine with a decrease in serum uric acid level. However, it is said that when overdosed in patients with renal failure, a large amount of oxypurinol accumulates in the blood and causes fatal poisoning syndrome.

  In view of the above, a therapeutic agent for hyperuricemia has been desired that can be taken safely and comfortably for a long period of time, for example, a product derived from a natural product that has been ingested daily since ancient times.

  However, very few have been disclosed as therapeutic agents for hyperuricemia derived from natural products or agents for lowering uric acid levels.

  For example, a uric acid level-lowering composition having a uric acid level-lowering effect derived from the genus Tochibanin ginseng plant has been proposed (see Patent Document 1).

  Further, a blood uric acid lowering agent containing melanin derived from squid or squid extract as an active ingredient and a functional food containing the uric acid lowering function have been proposed (see Patent Document 2).

  In addition, uric acid containing tea catechins as an active ingredient that lowers uric acid levels for those with high plasma uric acid levels and does not substantially vary for those with normal plasma uric acid levels A value reducing agent has been proposed (see Patent Document 3).

  Further, a xanthine oxidase inhibitor, a blood uric acid level-lowering agent, a hyperuricemia preventing or improving agent, a gout preventing agent, and a food and drink containing these agents, comprising a pomegranate extract as an active ingredient Drugs or cosmetics have been proposed (see Patent Document 4).

  A xanthine oxidase characterized by containing as an active ingredient a lemon extract obtained by extraction with a polar solvent selected from methanol, ethanol, and water, or an enzyme-treated product obtained by treating the lemon extract with β-glucosidase. Inhibitors (except when applied as food and drink) have been proposed (see Patent Document 5).

  In addition, a uric acid level reducing agent containing ginkgo biloba extract as an active ingredient has been proposed (see Patent Document 6).

  Moreover, the xanthine oxidase inhibitor which uses the squeezed juicer extract or extract as an active ingredient is proposed (refer patent document 7).

  Furthermore, as a patent document related to the present invention, regarding bacteria that have been disclosed as a therapeutic agent having a uric acid level lowering action or a uric acid level lowering agent from bacteria and fermentation extract in lactic acid fermentation,

  For example, to provide a lactic acid bacterium (Lactobacillus gasseri lactic acid bacterium OLL2922 strain) suitable for food and drink and pharmaceutical use and capable of preventing and / or treating hyperuricemia, and at the same time, hyperuricemia using the lactic acid bacterium A composition for prevention and / or treatment of infectious diseases has been proposed (see Patent Document 8).

Furthermore, uric acid in human serum can be obtained from ingredients derived from fermentation of barley and / or barley shochu distillation residue, through a simple treatment method suitable for actual production on a factory scale, without complicated purification steps. There have been proposed a serum uric acid level-lowering agent having an action of lowering the value and a food or drink with an indication that the serum uric acid level is decreased (see Patent Document 9).

Japanese Patent No. 5550995 JP2009-137896 Japanese Patent No. 4160276 JP 2006-16340 A Japanese Patent No. 5545692 Japanese Patent No. 4577998 International Publication Number WO2011 / 108059 Patent No. 5149305 Japanese Patent No. 50444643

  Patent Documents 1 to 6 describe active ingredients derived from natural products having an effect of improving hyperuricemia as described above, but include squeaker lactic acid fermented products, papaya lactic acid fermented products, and squeaked sour peel extracts. Not.

  Patent Document 4 has two effects of improving hyperuricemia: xanthine oxidase inhibitory effect and uric acid excretion promoting effect. However, regarding xanthine oxidase inhibitors, if xanthine oxidase does not work, uric acid synthesis is not performed and hypoxanthine and xanthine accumulate excessively in the body.

  Usually, hypoxanthine produced in the process of purine metabolism is reused for purine biosynthesis by the salvage circuit. The enzyme involved in the salvage cycle of purine metabolism is hypoxanthine-guanine-phosphoribosyltransferase (hereinafter referred to as “HPRT”). That is, the hypoxanthine that has become excessive by the action of HPRT is converted into inosinic acid (IMP) and reused for purine biosynthesis. Guanine, which is a precursor of xanthine, is also converted to guanylic acid (GMP) by the action of HPRT, which is also reused for purine biosynthesis. However, when the amount becomes too large to be processed by the salvage circuit, hypoxanthine and xanthine accumulate in the body, and xanthineuria develops.

  In xanthinuria, hypouricemia is inevitable, and excess xanthine precipitates in the urine, resulting in urolithiasis. It has also been reported that myalgia and arthritis due to accumulation of oxypurine (mainly xanthine and hypoxanthine) also occur as symptoms.

  Patent Document 7 describes a xanthine oxidase inhibitor in squeak juicer juice and aqueous solvent extract, which is obtained by determining the xanthine oxidase inhibition rate with a fluorescence spectrophotometer and has high inhibitory activity. It was only a matter of examining this and not the uric acid level. Moreover, it does not describe the factor (uric acid transporter) related to the promotion of uric acid excretion, and does not describe the seeker lactic acid fermented product and the papaya lactic acid fermented product.

  Patent Document 8 related to lactic acid fermentation of the present invention describes a patent for a living bacterium of Lactobacillus gasseri that has an effect of improving hyperuricemia by degrading purines and promoting absorption inhibition. However, it does not describe lactic acid fermented extracts of seeker and papaya.

  Moreover, in patent document 9, it describes that the active ingredient which has the effect which improves the hyperuricemia exists in the fermentation composition of a barley shochu distillation residue, and a residual liquid, performing fermentation with a koji mold. But it is not lactic acid fermentation.

  At present, patent documents for preventing and improving hyperuricemia mainly describe purine body absorption inhibition, uric acid synthesis suppression, and uric acid excretion promotion in the digestive tract.

The present invention is a natural product-derived, highly safe, and contains ingredients derived from Okinawa's special product, Shikuwasa, papaya, Shikuwasa peel extract, Shikuwasa lactic acid fermentation product, papaya lactic acid fermentation product and mixtures thereof, To provide a composition having the action of lowering the uric acid level in human blood by promoting the excretion of uric acid which excretes and promotes uric acid in the blood as urine without worrying about xanthineuria, hyperuricemia An object of the present invention is to provide a composition and a food and drink having an effect of improving and preventing the above.

  The present invention can solve the above-described problems by the following means.

  According to claim 1 of the present invention, there is provided a composition for promoting uric acid excretion, characterized in that a pressed liquid of seeker skin is used as an active ingredient.

 The Shikuwasa (Hirami Lemon: Citrus depressa Hayata) has long been known as a citrus fruit native to Okinawa, and is mainly produced in the Nagoya area or Izumi, mainly in Ogimi village in the northern part of the main island of Okinawa. The immature fruits contain a strong sourness and a rich aroma that are characteristic of seeker.

  The seeker contains several types of polymethoxyflavonoids such as nobiletin and tangeretin. In particular, tangeretin, nobiletin, and 5-demethylnobiletin are considered to have a cancer-suppressing effect, and nobiletin and sinensetin are used as rheumatoid arthritis. It is said that nobiletin has an effect of suppressing blood glucose level.

  The squeak juicer peel is the one after the squeak juicer's flesh has been separated, or the squeak juicer's fruit is squeezed to produce juice (water content of about 40%), and the juice is filtered and separated It is the later skin residue.

  The pressed liquid of the seeker skin is a juice obtained by applying the above-described seeker skin to a pressing machine (water content of about 20%). Manufacture of squeezed liquid can be performed in accordance with a conventional method, for example, well-known apparatuses, such as a screw press machine and a belt type press, can be used.

  According to a second aspect of the present invention, there is provided a composition for promoting uric acid excretion, characterized in that a crushed liquid of seeker skin is used as an active ingredient.

  The crushed liquid of the squeaker skin is a crushed liquid obtained by pasting the above squeaker skin into a paste using a mixer.

  Moreover, in Claim 3 of this invention, the mixture of the pressing liquid of said Claim 1 or the crushing liquid of said Claim 2, and the lactic acid fermented material of Sikhwasa peel is used as an active ingredient, It is characterized by the above-mentioned. It is a composition for promoting uric acid excretion.

  The lactic acid fermented product of the squeaker skin may be a fermented product obtained by subjecting the squeaked juicer skin to a press and subjecting the obtained juice to lactic acid fermentation to produce a fermented product. It is also good.

  The fermented product obtained by the lactic acid fermentation may be a lactic acid fermented product as it is, or a liquid and a residue obtained by filtration and separation.

  Lactic acid fermentation by the lactic acid bacterium is classified into, for example, Leuconostoc genus, Lactobacillus genus, Streptococcus genus, Bifidobacterium genus, Pediococcus genus, Enterococcus genus, and Pediococcus genus as lactic acid bacteria capable of lactic acid bacteria fermentation Lactic acid bacteria to be used.

  Specific examples of lactic acid bacteria that can be used in the present invention include Leuconostoc mesenteroides, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus brevis, Lactobacillus delbrueckii (more specifically, Lactobacillus delbrueckii subsp. Bulgaricus), Lactobacillus gasseri, Lactobacillus acidophilus, Lactobacillus caseophil (Lactobacillus casei), Streptococcus phil ), Streptococcus faecalis, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacteria Examples thereof include Bifidobacterium lactis and Bacillus mesentericus.

  In addition, the said lactic acid bacteria may be used independently and may be used in combination of multiple types of lactic acid bacteria.

  The content of the compressed liquid according to claim 1 or the crushed liquid according to claim 2 is preferably 20 to 80% by weight, more preferably 30 to 75% by weight, and more preferably 40%. ~ 70 wt%. Further, the content of the lactic acid fermented product of the seeker skin is preferably 3 to 50% by weight, more preferably 4 to 30% by weight, and more preferably 5 to 20% by weight.

  In the present invention, if fermentation is performed using lactic acid bacteria, the resulting fermented product has at least one of enzyme inhibitory activity and antioxidant activity.

  Examples of the enzyme inhibitory activity herein include tyrosinase inhibitory activity, lipase inhibitory activity, glucosidase inhibitory activity (for example, α-glucosidase inhibitory activity), and elastase inhibitory activity.

  Examples of the antioxidant activity here include superoxide dismutase activity (SOD activity).

  In performing fermentation, lactic acid bacteria should be added in an amount of 0.001 to 5 parts by mass, more preferably 0.002 to 1.0 parts by mass in terms of dry cell mass in the pre-culture with respect to 100 parts by mass of the seeker skin.

  In order to promote fermentation of lactic acid bacteria, lactic acid bacteria metabolic sugars and the like may be added. Of course, sugar may be added for the purpose of promoting fermentation and adding sweetness to the fermented product.

  When sugar is added, the type is not particularly limited, but it is preferable to add sugar that can be used for growth or fermentation of lactic acid bacteria. For example, sucrose, glucose, fructose, maltose and the like are preferably added. Of course, sugars other than the sugars exemplified here may be added.

  Moreover, you may add the yeast extract in the symbiotic relationship which helps the growth of lactic acid bacteria, glutamic acid which helps the GABA production increase of lactic acid bacteria, etc.

  In lactic acid fermentation, in order to create an environment in which lactic acid bacteria can proliferate preferentially, it is preferable to previously adjust the pH of the seeker skin by neutralization.

  Lactic acid fermentation is preferably performed under anaerobic conditions from the viewpoint of suppressing the decomposition of ascorbic acid. Anaerobic conditions can be, for example, by placing the squeaker skins in the fermenter and then degassing, or by sealing the fermenter, filling with a gas such as nitrogen or carbon dioxide, or depressurizing them, or It is obtained by combining. Moreover, the flavor of the fermented material obtained by performing fermentation on anaerobic conditions also becomes good.

  The conditions for lactic acid fermentation are not particularly limited. Fermentation temperature can usually be performed at 4 ° C to 50 ° C. What is necessary is just to set fermentation time suitably according to fermentation temperature, and when performing fermentation at 20 to 50 degreeC, 12 to 96 hours, More preferably, 24 to 96 hours are preferable.

  Furthermore, when performing low temperature fermentation of 4 degreeC-10 degreeC in order to raise flavor, 5 days-14 days are preferable.

  Lactic acid fermentation can be stopped by adding sugar. Examples of such sugars include sugar alcohols (for example, sorbitol), oligosaccharides (for example, maltooligosaccharide, chitooligosaccharide, fructooligosaccharide) and the like.

  Such oligosaccharides are effective for intestinal regulation, prevention of dental caries, and the like, and can impart functionality to the obtained fermented product.

  Lactic acid fermentation not only produces components useful in organic acid and oligosaccharides by assimilating the ingredients in the seeker skin, but it can also maintain the fermented product at a low pH, thus preventing the propagation of other bacteria. is there.

  In addition, since lactic acid bacteria are added, a fermented shikwasa peel with high physiological activity such as improved flavor, intestinal regulation and enzyme inhibition can be obtained.

  Moreover, in Claim 4 of this invention, the mixture of the pressing liquid of said Claim 1 or the crushing liquid of said Claim 2, and the lactic acid fermented product of papaya fruit is used as an active ingredient, It is characterized by the above-mentioned. It is a composition for promoting uric acid excretion.

  The papaya is an evergreen small Takagi tree belonging to the genus Papaya, and its scientific name is Carica papaya. It is cultivated in many tropical countries, and in Japan it grows naturally in the gardens of people in Okinawa.

  The leaves of this papaya (Carica Papaya) contain vitamin C, tannin, which has an antioxidant effect, vitamins A, E, K, saponin, iron, etc., digestion aids, anti-inflammatory effects, parasite control effects, etc. Has been reported.

  The papaya in the lactic acid bacteria fermentation of the papaya may be a papaya fruit washed, chopped or crushed, or a fruit juice that has been squeezed with a squeezing machine or the like, or a pressed residue. A papaya extract may also be used.

  The content of the compressed liquid according to claim 1 or the crushed liquid according to claim 2 is preferably 20 to 80% by weight, more preferably 30 to 75% by weight, and more preferably 40%. ~ 70 wt%. The content of the lactic acid fermented product of papaya fruit is preferably 3 to 50% by weight, more preferably 4 to 30% by weight, and more preferably 5 to 20% by weight.

  Moreover, in Claim 5 of this invention, the mixture of the pressing liquid of said Claim 1 or the crushing liquid of said Claim 2, the lactic acid fermented product of Sikhwasa peel, and the lactic acid fermented product of papaya fruit is effective. It is a composition for promoting uric acid excretion, characterized in that it is a component.

  The content of the compressed liquid according to claim 1 or the crushed liquid according to claim 2 is preferably 20 to 80% by weight, more preferably 30 to 75% by weight, and more preferably 40%. ~ 70 wt%. Moreover, content of the lactic acid fermented product of Sikhwasa skin and the lactic acid fermented product of papaya fruit is preferably 3 to 50% by weight, more preferably 4 to 30% by weight, and more preferably 5 to 20% by weight.

  According to a sixth aspect of the present invention, there is provided a food or drink comprising the uric acid excretion promoting composition according to any one of the first to fifth aspects as an active ingredient.

  The active ingredient of the uric acid excretion promoting composition of the present invention can be used as a raw material for various foods and drinks.

  The food and drink to be added is not particularly limited, for example, fruit drink, concentrated fruit juice, nutrition drink, alcoholic drink, soft drink, fermented food, seasoning, side dish, snacks, nutrition food, ice cream, Add to frozen desserts such as sherbet, desserts such as jelly, pudding, sheep candy, confectionery such as cookies, cakes, chocolate, chewing gum, buns, supplements such as tablets, tablet confections, soft capsules, hard capsules, tableting tablets, etc. be able to.

  The food and drink is a food and drink useful for the prevention and treatment of hyperuricemia by adding the above-described uric acid excretion-promoting composition as it is or by adding various nutritional components or adding it to known food or drink. be able to. Examples include fruit drinks, soft drinks, concentrated fruit juices, nutritional drinks, alcoholic drinks, gums, candy, cookies, and jelly.

The present invention has the following effects.
(1) A composition for promoting uric acid excretion can be provided.
(2) It is possible to provide a naturally derived uric acid excretion promoting composition that is safe even if taken for a long time.
(3) A uric acid excretion promoting composition derived from a seeker can be provided.
(4) A composition for promoting uric acid excretion derived from lactic acid fermentation of seeker and papaya can be provided.
(5) A composition for promoting uric acid excretion derived from a squeezed liquid or a crushed liquid obtained by squeezing a seeker skin can be provided.
(6) A uric acid excretion-promoting composition can be provided by a lactic acid fermentation of a seeker, a lactic acid fermentation of papaya, and a mixture of a pressed solution or a crushed solution of a seeker skin.
(7) By reducing the uric acid transporter gene Urat1, it is possible to provide a uric acid excretion promoting composition that inhibits the reabsorption of uric acid dissolved in urine into the blood in the proximal tubule and promotes uric acid excretion.
(8) A food and drink containing a composition for promoting uric acid excretion, which contains, as an active ingredient, a pressed liquid or a crushed liquid of squeak juicer peel, lactic acid fermentation of squeaker, lactic acid fermentation of papaya, or various mixed solutions, can be provided.

  Next, an embodiment of the present invention will be described.

(Manufacture of pressed liquid of shikwasa peel)
After washing the fruit of the seeker, it was squeezed with a press (water content 40%) to obtain a residue after filtration and separation. The residue was further subjected to a pressing machine (water content 20) to obtain a pressed liquid of seeker skin.

(Manufacture of fermented lactic acid lactic acid)
After washing the fruit of the seeker, the residue after squeezing with a belt type press was used as the seeker skin. Lactic acid bacteria (0.002 parts by mass) pre-cultured with yeast extract, glucose, and water are added to 100 parts by mass of shikwasa peel, and yeast extract, glucose, and sodium glutamate are added, and fermented at 30 ° C. for 96 hours. I let you. Lactobacillus brevis NBRC 12005 (Lactobacillus brevis) was used as the lactic acid bacterium. After completion of the fermentation, the mixture was filtered with 50 mesh to obtain a seeker lactic acid fermentation broth.

(Manufacture of fermented papaya lactic acid)
After washing the papaya fruit, the fruit skin is crushed with a food processor, squeezed with a squeezing machine, and the squeezed squeezed liquid is filtered with 100 mesh, and the filtrate is diluted to 60% with purified water. A pressed liquid was obtained. Lactic acid bacteria (0.002 parts by mass) pre-cultured with yeast extract and glucose were added to 100 parts by mass of the pressurizing solution, and sodium glutamate was added, followed by fermentation at 30 ° C. for 96 hours. Lactobacillus brevis NBRC 12005 (Lactobacillus brevis) was used as the lactic acid bacterium. After completion of the fermentation, the mixture was filtered with 50 mesh to obtain a papaya lactic acid fermentation broth.

Example 1
(Test sample 1: Preparation of seeker skin peel extract)
A 100% pressed solution of the above seeker skin was used.
Nobiletin was measured by high performance chromatography (HPLC). It was 70 mg / 100 ml-100 mg / 100 ml.

(Example 2)
(Test sample 2: Preparation of lactic fermented beverages of seeker and papaya)
Shikuwasa peel pressing 60%, Shikuwasa lactic acid fermentation 10%, papaya lactic acid fermentation 10%, Shikuwasa fruit 5%, seasoning 1.5%, acidulant 0.2%, sweetener 0.2%, flavor 0 A seeker fruit drink was formulated with 1% and 13% water.
Nobiletin was measured by high performance chromatography (HPLC). It was 50 mg / 100 ml.

(Test 1)
(Model mouse test 1)
Using mice (C57BL / 6NJcl, male, 6 weeks old, 20 ± 2 g), the test was carried out with 5 animals per group and 4 groups. A drug that increases uric acid levels using potassium oxonate (250 mg / kg) as a model mouse control, a drug that decreases uric acid levels using allopurinol (10 mg / kg) as a positive control, and test sample 1 A test group was prepared in which potassium oxonate was administered intraperitoneally, and physiological saline, allopurinol, and test sample 1 were administered intraperitoneally in the second administration. The administration interval was 1 hour and the dosage was 0.5 ml. One hour after the second administration, whole blood was collected and uric acid was measured. FIG. 1 shows an outline of the model mouse test.

FIG. Model mouse test 1

(Measurement of serum uric acid level in model mouse test 1)
As a result of measuring the uric acid level in the serum of the model mouse collected in the model mouse test 1, the prototype sample was 5.8 mg / dL compared to the model mouse control 7.5 mg / dL as shown in FIG. Decrease in uric acid level was confirmed.

FIG. Measurement result of serum uric acid level in model mouse test 1


(Test 2)
(Model mouse test 2)
Using mice (C57BL / 6N, male, 4-6 weeks old, 20 ± 2 g), the test was carried out with 5 animals per group and 5 groups. Each mouse raises uric acid level using potassium oxonate (250 mg / kg), model mouse control (saline) group, positive control to lower uric acid level, benzbromarone (10 mg / kg) test group, and allopurinol (10 mg / kg) The test was conducted using the test group, the test sample group 1 and the test sample group 2.
A test group was prepared in which potassium oxonate was administered intraperitoneally in the first administration, and physiological saline, benzbromarone, allopurinol, test sample 1 and test sample 2 were administered intraperitoneally in the second administration, respectively. The administration interval was 1 hour, the dosage was 0.5 ml, and this was performed continuously for 7 days, and urine was collected each day. Seven days after administration, whole blood was collected from each mouse and nephrectomy was performed, and uric acid in blood and urine was measured. FIG. 3 shows an outline of model mouse test 2.

FIG. Model mouse test 2

(Measurement of blood uric acid level in model mouse test 2)
As a result of measuring the uric acid level in the blood of the model mouse collected in the model mouse test 2, as shown in FIG. 4, the benzbromarone test group was found to be 3.2 mg / dL as compared with the model mouse control 6.4 mg / dL. The alpurinol test group was 0.1 mg / dL, test sample 1 was 4.5 mg / dL, test sample 2 was 5.8 mg / dL, and a decrease in blood uric acid levels could be confirmed in both test samples. It was.

FIG. Measurement results of blood uric acid level in model mouse test 2

(Measurement of urinary uric acid in model mouse test 2)
As a result of measuring the uric acid level in the urine of the model mouse collected by the model mouse test 2, it is shown in FIG. The uric acid level in urine was corrected as a creatinine ratio. Average values for 2 days before administration and 3 days after administration are shown.
As shown in FIG. 5, in the test sample 1, the test sample 2, and the benzbromarone test group, the uric acid level after administration is higher than that before administration. On the other hand, in the alpurinol test group, the uric acid level after administration has increased significantly.
In the allopurinol test group, which has the effect of suppressing uric acid production, there is no urinary uric acid excretion promoting effect, whereas in the benzbromarone test group, which is effective in promoting urinary uric acid excretion, The uric acid level of urine has increased significantly.
Also in Test Sample 1 and Test Sample 2, the uric acid level after administration was increased similarly to the benzbromarone test group, and the action of promoting uric acid excretion in urine was clearly confirmed.

FIG. Result of urinary uric acid measurement in model mouse test 2

(Test 3)
(Comparison of gene expression level of uric acid transporter)
Research on the mechanism of reabsorption and secretion of uric acid has progressed, and we focused on multiple uric acid transporters and compared test samples. As shown in FIG. 6, the uric acid reabsorption mechanism involves a uric acid transporter called URAT1 on the luminal membrane of the proximal tubular epithelial cell and GLUT9 on the blood vessel side, and transports uric acid from the epithelial cell to the blood vessel side. Is going. URAT1 is an exchange transporter, and uptake of uric acid via URAT1 is physiologically performed as exchange transport with intracellular lactic acid or nicotinic acid. For this reason, RNA is extracted from the mouse kidneys of each group of model mouse test 2, focusing on the Urat1 gene that acts to reabsorb uric acid and comparing the expression level of the Urat1 gene by real-time PCR. It was.

FIG. Uric acid transporter gene

(Results of URAT1 mRNA expression level comparison)
FIG. 7 shows the result of comparison of the expression level of URAT1 gene mRNA.
As shown in the figure, the expression level of the URAT1 gene tends to increase in the allopurinol test group compared to the model mouse control.
On the other hand, the test group of test sample 1 and test sample 2 showed a tendency to decrease the expression level of the URAT1 gene.
As a result, lactic acid discharged into the tubule in the kidney is inhibited from transporting uric acid from the proximal tubule to the blood vessel, and as a result, promotes the action of increasing uric acid excretion into the urine.

FIG. Comparison of URAT1 mRNA expression level

(Example 2)
(Human test)
(Production of lactic acid culture solution)
Lactic acid bacteria (1 g) were added to yeast extract (300 g), glucose (600 g), and water (29.1 Kg), followed by fermentation at 30 ° C. for 24 hours. Lactobacillus casei) LC-Ikematsu strain (Lactobacillus casei) was used as the lactic acid bacterium. After completion of the fermentation, the mixture was filtered with 50 mesh to obtain a lactic acid culture solution.

(Test sample 3: Preparation of seeker jelly)
Shikuwasa peel pressed 50%, Shikuwasa lactic acid fermentation broth 10%, papaya lactic acid fermentation broth 10%, sugar 13%, Shikuwasa juice 5%, lactic acid broth 4%, seasoning 0.5%, acidulant 1%, gel Test sample jelly was prepared with a composition of 1% of an agent, 0.1% of a sweetener, and 5.4% of water, and 25 g each was used as a jelly in a tube.

(Test 3)
(Human test method)
Ten randomly selected subjects took 100g (25g x 4) of test sample 3 for one week before meals, and blood UA (uric acid) levels at the time before and one week after the start of the test. Was measured.

(Changes in blood UA levels in human studies)
Regarding the results of changes in blood UA levels in human tests, 2 individuals with an inflammatory reaction were excluded from the individual data, and as shown in FIG. A decrease was observed. None of the examiners experienced any side effects during the intake period, and there was no resistance during intake.

FIG. Changes in human blood UA levels

Claims (6)

A composition for promoting uric acid excretion, characterized by comprising a pressed solution of shikwasa peel as an active ingredient.
A composition for promoting uric acid excretion, comprising a crushed liquid of shikwasa peel as an active ingredient.
A composition for promoting uric acid excretion, comprising as an active ingredient a mixture of the compressed liquid according to claim 1 or the crushed liquid according to claim 2 and a lactic acid fermented product of seeker skin.
A composition for promoting uric acid excretion, comprising as an active ingredient a mixture of the compressed liquid according to claim 1 or the crushed liquid according to claim 2 and a lactic acid fermented product of papaya fruit.
The uric acid excretion characterized by comprising as an active ingredient a mixture of the pressing liquid according to claim 1 or the crushed liquid according to claim 2, a lactic acid fermented product of seeker skin, and a lactic acid fermented product of papaya fruit Accelerating composition.
  A food or drink comprising the uric acid excretion promoting composition according to any one of claims 1 to 5.