JPH09208473A - In vivo cholesterol metabolic regulator and its use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an in vivo cholesterol metabolic regulator containing purine nucleotide. SOLUTION: This in vivo cholesterol metabolic regulator contains a purine nucleotide such as inosinic acid or guanylic acid, and further cytidylic acid or uridylic acid, as necessary. The agent contains a weight ratio of (inosinic acid/guanylic acid) of (1/10)-(10/1) and in a case of combinedly using pyrimidine nucleotide, a weight ratio of (purine nucleotide/pyrimidine nucleotide) of (1/5)-(5/1) to obtain a composition. This in vivo cholesterol metabolic regulator and a nucleotide composition have an action controlling in vivo cholesterol metabolism to reduce LDL concentration and increase HDL concentration in blood serum, and are useful for preventing and improving of hypercholesterolemia, etc. The dosage of 1-1,000mg for an adult par day is ingested or administers by devising to one several times.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a metabolic regulator of cholesterol in vivo and its use.

[0002]

2. Description of the Related Art Hypercholesterolemia is an abnormal increase in cholesterol in serum lipids and is considered to be one of the factors that cause arteriosclerosis. Cholesterol is mostly present in low density lipoprotein (LDL) and the majority of the rest in high density lipoprotein (HDL). Since LDL has a function of supplying cholesterol to extrahepatic tissues, when the blood concentration of LDL becomes high, excess cholesterol is supplied to cause arteriosclerosis. on the other hand,
HDL acts exactly opposite to LDL, which transfers excess cholesterol from extrahepatic tissues to the liver.
Conventionally, for the prevention and treatment of hypercholesterolemia, diet therapy such as ingestion of low-cholesterol food, use of cholesterol absorption inhibitors such as β-sitosterol and cholesterol synthesis inhibitors such as clofibrate, etc. are known. However, these are L in serum
Both the effect of lowering the DL concentration and the effect of increasing the HDL concentration were not sufficiently satisfied.

On the other hand, regarding the physiological functions of nucleotides that are a constituent of nucleic acids and are universally present in all living things,
In recent years, interest has come to the fore. Under these circumstances, the addition of nucleotides during lactation promotes maturation of the small intestine and growth of Bifidobacteria in the intestine (Kosaburo Ito, Kobe Medical University Bulletin, 29, 1, (1968)), and milk containing nucleotides added to infants. Changes in the blood lipoprotein concentration were observed (Nutr. Res., Vol. 6, p. 763-771, (1986), Ac
ta Paediatr., Vol.83, No.5, p.481-485, (1994), Pediat
r.Res., Vol.35, No.1, p.112-116, (1994)) has been reported.

[0004]

However, the reports on the physiological function of nucleotides so far have been aimed at the lactation period and not at the growing stage of adults and the like. Therefore, the effect of nucleotides on cholesterol metabolism during the growth period has not been clarified yet. Therefore, the present invention aims to provide a nucleotide composition which has an action effect of lowering LDL concentration in serum and increasing HDL concentration, and is particularly useful for prevention and treatment of the onset of hypercholesterolemia. is there.

[0005]

DISCLOSURE OF THE INVENTION As a result of repeated studies on the physiological function of nucleotides, the present inventors have found that a specific nucleotide and a composition containing the nucleotide have a favorable influence on the regulation of cholesterol metabolism in the growing period. Then, they have completed the present invention. That is, the present invention relates to an in vivo cholesterol metabolism regulator, which comprises a purine nucleotide as an active ingredient. The present invention also relates to a nucleotide composition containing inosine acid and guanylic acid as active ingredients and having an action of regulating cholesterol metabolism in the living body. Hereinafter, the present invention will be described in detail.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The in vivo cholesterol metabolism regulator of the present invention is characterized by containing at least a purine nucleotide, and optionally a pyrimidine nucleotide. Purine nucleotides used include inosinic acid (IMP) or guanylic acid (GM
P), and pyrimidine nucleotides include cytidylic acid (CMP) or uridylic acid (UMP).
Is mentioned. These nucleotides are at the 2'position, 3 '
It may have phosphoric acid at any of the 5'-position and the 5'-position. The nucleotide used may be in the form of a salt. Examples of such a salt include various metal salts such as alkali metal salts such as sodium salt and potassium salt and alkaline earth metal salts such as calcium salt. be able to.

Among such nucleotides, 5'-inosinate disodium (5'IMP-2N), which has already been approved as a food additive, is particularly preferable.
a) 5'-Disodium guanylate (5 'GMP-2
Na), 5'-disodium cytidylate (5'CMP-
2Na), 5'-uridylic acid disodium (5 'UMP
-2Na) and the like.

The combination of nucleotides is not particularly limited as long as it can exert an action of regulating the metabolism of cholesterol in the living body. Among them, a nucleotide composition containing IMP and GMP, or the composition A preferable example is a nucleotide composition in which a pyrimidine nucleotide is further added to the product. The blending ratio in the nucleotide composition is not particularly limited, and the IM in terms of weight ratio is calculated.
P: GMP = 1 to 10:10 to 1, preferably 1 to 5:
It can be appropriately selected from the range of 5 to 1. Furthermore, when a pyrimidine nucleotide is used in combination, it may be appropriately selected within the range of purine nucleotide: pyrimidine nucleotide = 1 to 5: 5-1, preferably 1-3: 3-1 in terms of weight ratio.

The in vivo cholesterol metabolism regulator and the nucleotide composition of the present invention are ingested or administered to a human (eg, a person with hypercholesterolemia) who intends to regulate cholesterol metabolism in the form of food or drink. . When taking the form of food and drink, the target food and drink may be in the form of food and drink to be eaten daily, including various hospital foods, nutritional supplements, etc., for example, powder, granules,
The type and form of food such as solid, liquid, and semi-liquid are not particularly limited. In these various foods and drinks, for example, nucleotides can be ingested in an amount required for expression of action by appropriately adding nucleotides at the time of production or eating and drinking.

Further, it can be used in a form other than food and drink. For example, in the case of a pharmaceutical product or a form similar thereto, any of its preparation methods can be performed according to a conventional method, such as a liquid form such as a drink and a syrup, an oral form such as a solid form such as a tablet, capsule and granule. Can be used in. Carriers, excipients and other additives used at this time are not particularly limited, for example, lactose, kaolin, crystalline cellulose, talc, agar, pectin, stearic acid, starch, solids such as sodium chloride, water Glycerin, peanut oil, polyvinyl hydrin, ethanol, benzyl alcohol, propylene glycol and the like.

[0012] The ingestion amount or dose of the in vivo cholesterol metabolism regulator and the nucleotide composition of the present invention may vary depending on the health condition, the degree of cholesterol in blood, age, weight,
1 to 1000 mg / day for adults, depending on gender
As a guideline, the dose may be appropriately increased or decreased to be ingested or administered in a single dose to multiple doses a day.

[0012]

INDUSTRIAL APPLICABILITY The agent for regulating cholesterol metabolism in vivo and the nucleotide composition of the present invention favorably regulate cholesterol metabolism in the body such that the LDL concentration in serum is decreased and the HDL concentration is increased. Since it has an action, it is useful for prevention and amelioration of hypercholesterolemia, for example.

[0013]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited thereto. Example: A control group (first group) fed with 25 normal Wistar rats (4 weeks old), the composition of the present invention (5′UMP-2Na: 5′CMP-2Na: 5′GM)
P-2Na: 5'IMP-2Na = 1: 1: 1: 1) -added feed-added nucleotide group (second group), composition of the present invention (5'GMP-2Na: 5'IMP-2Na =
1: 1) was added to each of the purine nucleotide groups (third group) to which the feed was added, and each feed was given. Table 1
Shows the feed formulation.

[0014]

[Table 1]

Rats in each group were fed with each of the above diets for 20 days, then fasted overnight, and blood was collected from the abdominal vena cava to separate plasma, and the concentration of lipid contained in the blood collected from each individual was kept constant. It was measured by the method. The lipids measured were plasma triglyceride (TG) and plasma total cholesterol (T
C), HDL cholesterol and LDL cholesterol, and the measurement results, average values and standard deviations thereof were determined.

[0016]

[Table 2]

[0017]

[Table 3]

[0018]

[Table 4]

[0019]

[Table 5]

An arteriosclerosis index was determined from the above measurement results.

[0021]

[Table 6]

From the above-mentioned results, in both the second group and the third group fed with the composition-containing feed of the present invention, compared with the control group (first group), LDL in blood did not significantly change TC and TG. Lowers cholesterol levels and HDL
It was clarified that the cholesterol concentration could be increased and the arteriosclerosis index was also decreased as compared with the control group. From this, it was shown that the composition of the present invention is useful for regulating the metabolism of cholesterol, and particularly, can be used for prevention and treatment of hyperlipidemia.

Claims (6)

[Claims] 1. An in vivo cholesterol metabolism regulator, which comprises a purine nucleotide. 2. The in vivo cholesterol metabolism regulator according to claim 1, wherein the purine nucleotide is inosinic acid or guanylic acid. 3. The in-vivo cholesterol metabolism regulator according to claim 1, further comprising cytidylic acid and / or uridylic acid. 4. A nucleotide composition containing inosine acid and guanylic acid as active ingredients and having an action of regulating cholesterol metabolism in the living body. 5. The nucleotide composition according to claim 4, further comprising cytidylic acid and / or uridylic acid. 6. A food or drink comprising the in vivo cholesterol metabolism regulator according to claim 1 or the nucleotide composition according to claim 4.