HK1171372A - Composition for lowering blood uric acid level - Google Patents

Description

Composition for reducing uric acid level in blood

Technical Field

The present invention relates to a composition for reducing uric acid level in blood, which contains taurine as an active ingredient.

Background

Modern Japanese's dietary life is a trend with the westernization towards a high-fat, high-energy diet. As a result, unhealthy conditions such as obesity are also caused. Furthermore, the increase in uric acid level in the living body is caused by drinking, stress, or the like.

In general, most of uric acid is excreted to the outside of the body together with urine, sweat, stool, and the like in a healthy state, but if uric acid synthesis is excessive and excretion is not smoothly performed due to the above-mentioned influence of dietary life or living environment, the amount of uric acid in blood becomes excessive. As described above, a state exceeding the saturation solubility of uric acid in blood (7.0mg/dL) is hyperuricemia.

In hyperuricemia, in which the uric acid level in blood is constantly high, sodium urate crystals start to deposit in body tissues, and crystals are likely to form at low body temperature, and therefore, they accumulate in legs and earlobes in many cases. If uric acid crystals are deposited at the base of the thumb or knee joint where the crystals are particularly prone to accumulate, inflammation is caused and severe pain (gout attack) is also accompanied. In addition, when calculus occurs in the renal tubules, renal dysfunction is also caused.

Taurine (aminoethanesulfonic acid) is known as a sulfur-containing amino acid having a molecular weight of 125.15 and a very simple chemical structure, and its pharmacological effects are related to a wide range including the cranial nerve system, circulatory system, and hepatobiliary system. In particular, taurine has been found to have an action of reducing serum cholesterol, and a main action mechanism thereof is considered to be an action of promoting the catabolic excretion of cholesterol from the liver (see non-patent documents 1 to 4). Further, taurine-containing preparations have been sold for a long time in the field of prescription drugs, over-the-counter drugs, or quasi drugs, and in japan, 50 years have passed since the initial distribution of taurine-containing preparations. Therefore, taurine itself is sufficiently used in the actual state, and is one of the components having extremely high safety.

Documents of the prior art

Non-patent document

Non-patent document 1: murakami, s., Kondo, y., Toda, y., Kitajima, h., Kameo, k., Sakono, M and Fukuda, N: effect of source on cholestatolism in hamsters: up-regulation of Low Density Lipoprotein (LDL) receptor by taurine (action of taurine on cholesterol metabolism in hamsters: taurine Up-regulates Low Density Lipoprotein (LDL) receptors), Life Sci.70: 2355-2366, 2002.

Non-patent document 2: yokogoshi, H., Mochizuki, H., Nanami, k., Hida, y., Miyachi, F and Oda, H: dietary taurine enhanced cholesterol degradation and reduced serum and liver cholesterol concentrations in high cholesterol fed rats, j.nutr.129: 1705-1712, 1999.

Non-patent document 3: murakami, s., Kondo Y and Tomisawa, K: improvement in cholesterol metabolism in mice fed with taurine long-term treatment and a high-fat diet, Life sci.64: 83-91, 1999.

Non-patent document 4: yu Zhao, Yuchuan wuwu, Yangtian confortunes, Xicun straight road, crossing over the X-ray-shaped armor: タウリンによる CYP7A1 (ancient organism ) (mechanism for taurine inducing CYP7A1 gene expression): must アミノ acid 167, 13-16, 2003.

Disclosure of Invention

Problems to be solved by the invention

The causes of hyperuricemia and gout include the above-mentioned excess production of uric acid and low excretion, and at the time of gout attack, inflammation is suppressed by administering a nonsteroidal anti-inflammatory analgesic. In addition, for the purpose of lowering the uric acid level, treatment for lowering the uric acid level is performed by administering an oral drug in the case where the uric acid level exceeds 9.0mg/dL in addition to improvement of living habits such as dietary life.

The agents for lowering uric acid level include uric acid production inhibitors and uric acid excretion promoters, but when these agents are taken, it is necessary to increase the amount of urine by sufficiently taking in water, and sodium bicarbonate or a urine alkalinizing agent is used to maintain the pH of urine at 6.0 to 6.5 in order to keep the urine alkaline.

In addition, in any case of using any drug, it is necessary to periodically check the uric acid level and continuously control the uric acid level, and the treatment is often lifelong. When these agents are used, the uric acid level is unnecessarily lowered, or adverse effects such as urinary calculi caused by the agents may be observed. Such a drug which is administered for a long period of time is required to have high safety as well as high efficacy.

Accordingly, an object of the present invention is to provide a composition which suppresses an increase in blood uric acid level, which is a cause of hyperuricemia or gout, and which is safe and highly effective even when taken for a long period of time.

Means for solving the problems

The present inventors have made extensive studies to solve the above problems, and as a result, have found that taurine has an action of lowering the uric acid level in blood, thereby completing the present invention.

The present invention is a composition for reducing uric acid level in blood, comprising taurine as an active ingredient.

The preferred embodiment of the present invention is the above-mentioned composition as a prophylactic or therapeutic agent for hyperuricemia.

Another preferred embodiment of the present invention is the above composition as a prophylactic or therapeutic agent for gout.

Another preferred embodiment of the present invention is the above composition as an internal preparation.

Effects of the invention

The present invention provides a composition for reducing uric acid level in blood, which contains taurine as an active ingredient and is safe even when administered for a long period of time.

Brief Description of Drawings

FIG. 1 is a graph showing the change in serum uric acid values in a taurine administration group and a placebo administration group.

Fig. 2 is a graph showing changes in uric acid clearance values (at the start of administration) in the taurine administration group and the placebo administration group.

Fig. 3 is a graph showing changes in uric acid clearance values (at the end of administration) in the taurine administration group and the placebo administration group.

FIG. 4 is a graph showing the change in serum uric acid level in each subject.

Detailed Description

The present invention provides a composition for reducing uric acid level in blood, which is characterized by containing taurine as an active ingredient.

The composition of the present invention may be in the form of a pharmaceutical composition, a food or drink, or a reagent for research purposes (e.g., in vivo experiments).

The composition of the present invention has an action of lowering the uric acid level in blood, and therefore, can be suitably used as a pharmaceutical composition to be administered for preventing or treating a disease (e.g., hyperuricemia, gout, or the like) caused by an increase in the uric acid level in blood, and can also be suitably used as a food or drink to be taken on a daily basis for lowering the uric acid level in blood.

The composition of the present invention can be formulated by a known formulation method. For example, it can be used orally or parenterally in the form of tablet, granule, powder, capsule, pill, fine granule, film coating, pellet, buccal tablet (トロ - チ), sublingual tablet, chewable tablet, buccal tablet (バツカル agent), liquid, syrup, suspension, elixir, emulsion, paste, aerosol, injection, suppository, etc.

These preparations may be appropriately combined with carriers acceptable pharmacologically or as foods and beverages, specifically, sterile water or physiological saline, vegetable oils, solvents, base agents, emulsifiers, suspending agents, surfactants, stabilizers, flavoring agents, aromatics, excipients, vehicles, preservatives, binders, diluents, isotonic agents, extenders, disintegrating agents, buffers, coating agents, lubricants, colorants, sweeteners, tackifiers, flavors, solubilizers, or other additives.

When the composition of the present invention is used as a pharmaceutical composition, it is preferably provided as an oral preparation such as an oral solid preparation or an oral liquid preparation.

When the solid preparation for internal use is prepared, for example, other known additives such as taurine can be granulated and provided in the form of tablets, granules, powders, capsules, and the like.

For example, other known additives such as taurine can be dissolved in water and provided in the form of a drinkable preparation.

When the composition of the present invention is used as a pharmaceutical composition, 1 or 2 or more other components effective for preventing or treating a disease caused by an increase in uric acid level in blood may be blended. In addition, the composition may be used in combination with another pharmaceutical composition effective for preventing or treating a disease caused by an increase in uric acid level in blood.

In the pharmaceutical composition of the present invention, for example, citric acid (having an action of maintaining weak alkalinity of urine so as to make uric acid easily dissolved in urine), vitamin C (having an action of moving uric acid accumulated in joints and the like to the kidney and promoting excretion of uric acid), potassium (having an action of promoting filtration of uric acid by the kidney), folic acid (having an action of reducing activation of uricolytic enzyme), and the like may be appropriately added in addition to taurine within a range not impairing the effects of the present invention.

When the composition of the present invention is used as a food or drink, the food or drink may be, for example, a health food, a functional food, a food for specified health use, a nutritional supplement food, a food for patients, or a food additive. The food or drink of the present invention can be taken as various foods or drinks in addition to the composition described above. Specific examples of the food and drink include liquid foods such as beverages, soups, milk beverages, refreshing drinks, tea beverages, alcoholic beverages, frozen beverages, and functional beverages; edible oil, sauce, mayonnaise, artificial butter, etc; carbohydrate-containing foods such as rice, flour, bread, etc.; processed food of livestock such as ham and sausage; fish cake, dried aquatic product (dry product), and salt fermented aquatic product (salt form) such as processed food; processed food of vegetables such as pickled vegetables; semi-solid food such as jelly and yogurt; fermented foods such as sauce and fermented beverage; various snacks such as western-style snacks, japanese snacks, candies, chewing gums, gummy candy (Gummi), refrigerated snacks, and ice-cold snacks; curry, sauce (あ once かけ), Chinese soup (Chinese soup) and other cooking products; instant food such as instant soup and instant sauce, and food corresponding to microwave oven. Further, the food or drink may be prepared into a powder, a granule, a tablet, a capsule, a liquid, a paste or a jelly.

The food or drink of the present invention can be produced by a production technique known in the art. The food or beverage may contain 1 or more than 2 components effective in reducing uric acid level in blood. In addition, the composition can be used as a multifunctional food or drink by combining with other components or other functional foods that exhibit functions other than the function of lowering the uric acid level in blood.

In the food or drink of the present invention, for example, citric acid (having an action of maintaining weak alkalinity of urine so as to make uric acid easily dissolved in urine), vitamin C (having an action of moving uric acid accumulated in joints and the like to the kidney and promoting excretion of uric acid), potassium (having an action of promoting filtration of uric acid by the kidney), folic acid (having an action of reducing activation of uricolytic enzyme), and the like may be appropriately blended in addition to taurine within a range not impairing the effects of the present invention.

When the composition of the present invention is administered or ingested, the administration amount or the intake amount thereof can be appropriately selected according to age, body weight, symptoms, health status, type of composition (drug, food, drink, etc.), and the like. The composition of the present invention contains taurine in an effective amount of 100mg to 6000mg, preferably 500mg to 4000mg, and more preferably 2000mg to 4000mg per day for an adult. The present invention also provides a method for reducing uric acid level in blood of a subject, characterized by administering the composition of the present invention to the subject or allowing the subject to ingest the composition of the present invention as described above. Further, there is provided a method for preventing or treating a disease caused by an increase in blood uric acid level in a subject, which is characterized by administering the composition of the present invention to the subject.

The product of the composition of the present invention (drug, food, drink, reagent) or the instructions thereof may be accompanied by an expression for lowering the uric acid level in blood. The term "article or a description attached with a representation" means that a representation is attached to a body, a container, a package, or the like of the article or a representation is attached to a description, an attached document, a poster, other printed matter, or the like, which discloses article information. The expression for lowering the uric acid level in blood may contain information on a mechanism for lowering the uric acid level in blood by administering or taking the composition of the present invention. The expression for lowering the uric acid level in blood may contain information on a disease for preventing or treating an increase in the uric acid level in blood.

Examples

The present invention will be described in more detail below with reference to examples and test examples

[ example 1]

Taurine 1000 mg/bag

Light anhydrous silicic acid 10 mg/bag

Talcum powder 10 mg/bag

Mixing the above components, wet granulating, drying, and making into powder.

[ example 2]

Mixing the above materials, dissolving in purified water, adjusting pH to 3.0 with sodium citrate, sterilizing at 95 + -5 deg.C, and making into oral liquid.

[ test example 1]

40 subjects considered to have lifestyle-related diseases and suitable for the following conditions were divided into 2 groups of 20 subjects each aged 20 years or older, and placebo and the powder prepared in example 1 were administered 2 times a day for 1 day within 14 days at 2.04g (2000 mg in terms of taurine amount) per time, and changes in uric acid values were confirmed by a random double-blind test.

In this test, a double screening test was performed before the test was started, and subjects satisfying all the conditions in the 1 st screening test under the following conditions 1 to 3 were selected as subjects of the 2 nd screening test, and further, subjects satisfying the condition 4 in addition to the conditions 1 to 3 were selected as subjects of the test at the 2 nd screening test in order to estimate that the in vivo taurine amount affects the result of the test. The results were distinguished for each administration group with the uric acid level of 7.0mg/dL as an index of hyperuricemia as a limit, and the uric acid levels of the groups were compared.

The results are shown in Table 1 below.

In addition, 1 case assigned to the taurine administration group was discontinued due to the finding of another disease before the start of administration.

Condition 1: LDL cholesterol of 140mg/dL or more

Condition 2: triglyceride 150mg/dL or more and less than 400mg/dL

Condition 3: total cholesterol above 220mg/dL

Condition 4: the excretion amount of taurine in urine (24 hours of urine storage) is less than 1500 mu mol

According to Table 1, in subjects with uric acid values above 7.0mg/dL, the mean increase in uric acid values of 0.03mg/dL and the median increase of 0.05mg/dL in the placebo-administered group was seen, whereas the mean decrease in taurine-administered group was seen to be 0.75mg/dL and the median decrease to 0.70 mg/dL. In addition, in comparison with the initial period, it was found that the uric acid level at the end of the administration was significantly decreased in the taurine administration group (P < 0.001), but there was no significant difference in the uric acid level at the initial period and the end of the administration in the placebo administration group. Also, a significant difference was seen between the taurine-administered group and the placebo-administered group (P ═ 0.020).

In addition, in the subjects with a uric acid level of less than 7.0mg/dL in the group to which taurine was administered, it was found that the mean value of the uric acid level was decreased by 0.05mg/dL and the median value was increased by 0.1mg/dL, but there was no significant difference in the uric acid level at the time of initiation and at the time of completion of the administration. In the taurine-administered group, when the layers having a uric acid level of 7.0mg/dL or more and less than 7.0mg/dL were compared, a significant difference was observed between the layers (P0.001).

The administration groups were differentiated by the limit of uric acid level at the beginning of 7.0mg/dL, and the results of comparison of the uric acid level variation frequency of each group are shown in Table 2 below.

TABLE 2

( )：％

According to Table 2, among subjects having a uric acid level of 7.0mg/dL or higher, 3 subjects (50.0%) with placebo-administered group had a reduced uric acid level as compared with the subjects at the beginning, and 3 subjects (50.0%) with no reduction (increased or unchanged uric acid level). On the other hand, all of the 8 subjects in the group to which taurine was administered had decreased uric acid values.

[ test example 2]

The oral liquid preparation prepared in example 2 was administered 1 time a day for 1 time in 8 weeks to 121 subjects considered to have lifestyle-related diseases suitable for the following conditions, which were over 20 years old. Further, similarly to test example 1, the uric acid values were compared in layers while being distinguished by the limit of the initial uric acid value of 7.0 mg/dL.

The results are shown in Table 3 below.

Condition 1: the serum triglyceride value is above 150mg/dL and less than 400mg/dL

Condition 2: serum total cholesterol value of more than 200mg/dL

According to Table 3, in subjects with a uric acid level of 7.0mg/dL or above, a 0.60mg/dL reduction in mean and a 0.55mg/dL reduction in median was observed, whereas in subjects with a uric acid level of less than 7.0mg/dL, a 0.14mg/dL reduction in mean and a 0.1mg/dL reduction in median was observed. Therefore, although the uric acid level tends to decrease in any group, a significant difference between the layers (P < 0.001) was observed when the uric acid levels were compared in each layer with the limit of 7.0 mg/dL.

The uric acid values were classified with the limit of 7.0mg/dL, and the results of comparing the frequency of uric acid value changes are shown in Table 4 below.

TABLE 4

( )：％

According to Table 4, the subjects with a uric acid level of 7.0mg/dL or higher had a uric acid level that was decreased from the beginning by 39 subjects (81.3%) and 9 subjects with no decrease (18.8%). Furthermore, in subjects with uric acid levels less than 7.0mg/dL, the uric acid levels were 37 subjects (50.7%) decreased from the beginning and 36 subjects (49.3%) not decreased from the beginning.

[ test example 3]

16 subjects considered to have hyperuricemia in the age of 20 or more and suitable for the following conditions were divided into 2 groups of 8 each, and placebo and the powder prepared in example 1 were administered 2 times a day for 1 day within 14 days at 2.04g (2000 mg in terms of the amount of taurine) per time, and changes in uric acid values were confirmed by a random double-blind experiment.

In this test, a double screening test was performed before the test was started, and subjects who satisfied the following conditions in the 1 st screening test were subjects of the 2 nd screening, and subjects who satisfied the conditions again in the 2 nd screening test were subjects of the test. Further, in order to confirm the change in uric acid clearance value that affects the change in uric acid value in this test, uric acid values and uric acid clearance values were measured at 4 time points, i.e., 1 hour before administration, 1 hour after administration, 2 hours after administration, 3 hours after administration, and 4 time points that are also the same at the end of administration, at the start of administration of taurine. In order to match the conditions at the start and end of administration, the subjects were hospitalized for 2 nights and 3 days before the respective measurements, and ingested on the same diet.

The results are shown in FIG. 1.

Note that 1 case assigned to the taurine administration group was discontinued because another disease was found during the 14 day administration period.

Conditions are as follows: serum uric acid level: 7.0mg/dL or more and less than 9.0mg/dL

As shown in FIG. 1, in comparison of the 1 hour before administration at the start of administration and the 3 hours after administration at the end of administration, it was found that the mean value of the group administered with taurine decreased by 0.53mg/dL, but the mean value of the group administered with placebo decreased by 0.18 mg/dL.

Further, similarly to test examples 1 and 2, the administration groups were differentiated with the uric acid level at the beginning being 7.0mg/dL, and the frequency of change in uric acid level was compared among the groups.

The results are shown in Table 5 below.

TABLE 5

( )：％

According to Table 5, among subjects having a uric acid level of 7.0mg/dL or higher, the placebo-administered group had a reduced uric acid level of 3 subjects (60.0%) and 2 subjects (40.0%) who were not reduced. On the other hand, all of the 4 subjects in the group to which taurine was administered had decreased uric acid values.

Next, the change (change rate) at the start of administration of the uric acid clearance value indicating the efficiency of uric acid excretion in each administration group was compared.

The results are shown in FIG. 2.

From fig. 2, it was found that the average change rate of the taurine administration group at the start of administration was increased by 40% or more at 2 hours after administration and increased by 30% or more at 3 hours after administration, but the change of the placebo administration group was hardly observed. In addition, significant differences were observed between the two administration groups at the time points of 1 hour, 2 hours, and 3 hours after the administration, and significant increases were observed when the values of the taurine administration group at 2 hours and 3 hours after the administration were compared with the values at 1 hour before the administration.

In addition, the change (change rate) at the end of administration of uric acid clearance value in each administration group was compared.

The results are shown in FIG. 3.

From fig. 3, at the end of the administration, the average change rate of the taurine administration group was increased by 30% or more at 2 hours after the administration and by 20% or more at 3 hours after the administration, but the placebo administration group was increased by about 10% at 2 hours after the administration. In addition, a significant increase was observed in the taurine administration group when the values at 2 hours and 3 hours after the administration were compared with the values at 1 hour before the administration.

It is clear from the change in uric acid clearance value that the effect of the present invention is due to the increase in the excretion efficiency of uric acid.

Next, the taurine administration examples of test examples 1 to 3 were ranked in order of the amount of change in serum uric acid level before and after administration from the subject having the larger value before administration.

The results are shown in FIG. 4.

In addition, the taurine administration examples of test examples 1 to 3 were combined, and the uric acid values at the beginning were classified into layers with the limit of 7.0mg/dL, and the amounts of change in the uric acid values were compared in each layer.

The results are shown in Table 6.

According to FIG. 4, subjects having a uric acid value of 7.0mg/dL or more had a higher frequency of lowering the uric acid value than those having a uric acid value of less than 7.0mg/dL, and according to Table 6, subjects having a uric acid value of 7.0mg/dL or more had a mean value of 0.62mg/dL and a median value of 0.60mg/dL, but subjects having a uric acid value of less than 7.0mg/dL had a mean value of 0.13mg/dL and a median value of 0.1 mg/dL. Therefore, although the uric acid level tends to decrease in any group, a significant difference (P < 0.001) was observed between the layers when the layers were compared with each other with the limit of the uric acid level of 7.0 mg/dL.

[ conclusion ]

As described above, according to the results of test examples 1 to 3, it was confirmed that taurine is an effective component of a prophylactic or therapeutic agent for hyperuricemia and an effective component of a prophylactic or therapeutic agent for gout caused by hyperuricemia, since oral administration of taurine can significantly reduce the uric acid level and that in subjects with a uric acid level of 7.0mg/dL or higher diagnosed with hyperuricemia, taurine is significantly reduced as compared with those in the normal range. Furthermore, in subjects with uric acid levels less than 7.0mg/dL, the frequency of lowering of the uric acid level by administration of taurine is low, and therefore, even when the uric acid level is lowered as seen, it is considered that even after the uric acid level becomes normal by administration of taurine in a hyperuricemia patient, and further, administration of taurine is continued, there is little possibility of problems, and safety is extremely high.

Industrial applicability

According to the present invention, a composition for reducing uric acid level in blood, which contains safe and highly effective taurine as an active ingredient, can be provided.

Claims (3)

1. A composition for reducing uric acid level in blood, characterized by containing taurine as an active ingredient.

2. The composition according to claim 1, which is a prophylactic or therapeutic agent for hyperuricemia.

3. The composition according to claim 1, which is a prophylactic or therapeutic agent for gout.