JP2010163403A - Isoprostane inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an isoprostane inhibitor and a renal function ameliorating agent containing natural active components. <P>SOLUTION: The isoprostane inhibitor contains a renal function ameliorating agent and a fatigue improving agent containing the following components (a) or (b): (a) at least one kind of glycerophospholipid selected from the group consisting of phosphatidylserine and phosphatidylinositol; and (b) a glycerophospholipid mixture obtained by reacting a vegetable-originated lecithin with serine in the presence of phospholipase D. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an isoplastane lowering agent and a renal function improving agent.

Isoprostane (sometimes referred to as isoprostane) is a prostaglandin-like lipid peroxide produced by oxidation of arachidonic acid, which is a phospholipid of cell membrane (Non-patent Document 1). ). The isoplastane produced in the cell membrane adversely affects the fluidity of the cell membrane, and thus impairs cell functions such as substance permeability and membrane-bound protein function.
In addition, isoplastane has various factors related to metabolic syndrome such as obesity (Non-patent document 2), hyperglycemia (Non-patent document 3), hypertension (Non-patent document 4), and lipid abnormality (Non-patent document 5). Correlation has been reported.
In addition, isoplastane is known to act on the kidney itself and cause a decrease in renal function such as a decrease in renal blood flow and a decrease in glomerular filtration rate (Non-patent Document 6).
Moreover, it is known that the isoplastane density | concentration in a body will increase with aging (nonpatent literature 7).
In addition, it is known that the concentration of isoplastane increases due to excessive exercise (Non-patent Document 8).
In general, isoplastane is known as a biomarker for lipid oxidation in living organisms and is used for evaluation of oxidative stress.
Accordingly, there is a demand for the development of drugs that lower the isoplastane concentration in the body.

J.D.morrow et al. (1992) Proc. Natl. Acad. Sci. USA 89: 10721-10725 H. Urakawa et.al. (2003) J. Clin. Endocrinol. Metab. 88: 4673-4676 G. Davi et al. (1999) Circulation 99: 224-229 J.A.Haas et al. (1999) Hypertension 34: 983-986 M.P.Reilly et al. (1998) Circulation 98: 2822-2828 J.D.marrow et al. (1990) Proc. Natl. Acad. Sci. USA 87: 9383-9387 Ward WF et al. (2005) J. Gerontol A Biol. Sci. Med. Sci. 60: 847-851 K. Margonis et al. (2003) Free Rad. BiolMed. 43: 901-910

  An object of the present invention is to provide an isoplastane lowering agent and a renal function improving agent containing natural active ingredients.

  The present inventor has conducted research in order to solve the above problems, and ingesting a glycerophospholipid mixture obtained by reacting lecithin derived from soybean and serine in the presence of phospholipase D, in blood and urine. It has been found that the isoplastane concentration of the is decreased. The glycerophospholipid mixture may contain phosphatidylserine (hereinafter also abbreviated as “PS”) and phosphatidylinositol (hereinafter abbreviated as “PI”) as main components. I found it.

The present invention has been completed based on these findings, and can provide the following isoplastane lowering agent and renal function improving agent, and further provide a fatigue improving agent.
Item 1. An isoplastane lowering agent comprising at least one glycerophospholipid selected from the group consisting of phosphatidylserine and phosphatidylinositol.
Item 2. Item 2. The isoplastane reducing agent according to Item 1, wherein the glycerophospholipid is phosphatidylserine and phosphatidylinositol.
Item 3. Item 3. The isoplastane reducing agent according to Item 2, wherein the weight ratio of phosphatidylserine and phosphatidylinositol is phosphatidylserine: phosphatidylinositol = 0.5 to 20: 1 in terms of dry weight.
Item 4. An isoplastane reducing agent comprising a glycerophospholipid mixture obtained by reacting plant-derived lecithin and serine in the presence of phospholipase D.
Item 5. A renal function improving agent comprising at least one glycerophospholipid selected from the group consisting of phosphatidylserine and phosphatidylinositol.
Item 6. Item 6. The renal function improving agent according to Item 5, wherein the glycerophospholipid is phosphatidylserine and phosphatidylinositol.
Item 7. Item 7. The renal function improving agent according to Item 6, wherein the weight ratio of phosphatidylserine to phosphatidylinositol is phosphatidylserine: phosphatidylinositol = 0.5 to 20: 1 in terms of dry weight.
Item 8. A renal function improving agent comprising a glycerophospholipid mixture obtained by reacting plant-derived lecithin and serine in the presence of phospholipase D.
Item 9. A fatigue ameliorating agent comprising at least one glycerophospholipid selected from the group consisting of phosphatidylserine and phosphatidylinositol.
Item 10. Item 11. The fatigue ameliorating agent according to Item 9, wherein the glycerophospholipid is phosphatidylserine and phosphatidylinositol.
Item 11. Item 11. The fatigue ameliorating agent according to Item 10, wherein the weight ratio of phosphatidylserine and phosphatidylinositol is phosphatidylserine: phosphatidylinositol = 0.5 to 20: 1 in terms of dry weight.
Item 12. A fatigue-improving agent comprising a glycerophospholipid mixture obtained by reacting plant-derived lecithin and serine in the presence of phospholipase D.

A glycerophospholipid mixture containing at least one member selected from the group consisting of PS and PI can lower the isoplastane concentration in the body by being administered as an active ingredient such as an oral agent, an injection, or a suppository. . Thereby, various symptoms caused by isoplastane can be improved, and typically renal dysfunction can be improved. Moreover, it is expected to improve various symptoms of metabolic syndrome such as obesity, hyperglycemia, hypertension, lipid abnormalities, various symptoms due to aging, and various symptoms due to fatigue, particularly physical fatigue.
Moreover, since this glycerophospholipid is a component derived from natural products such as soybeans, it is safe and can be produced by a naturally friendly method.

FIG. 3 is a graph comparing blood isoplastane concentration with a control when an obese model rat is fed with a diet containing PS / PI and a diet containing PS. It is the figure which compared the urinary isoplastane density | concentration at the time of administering the formulation containing PS * PI to the person who has an obesity tendency with the density | concentration before administration.

The present invention will be described in detail below.
(I) Isoplastane reducing agent The first isoplastane reducing agent of the present invention contains at least one glycerophospholipid selected from the group consisting of PS and PI as an active ingredient. Moreover, the 2nd isoplastane reducing agent of this invention contains the glycerophospholipid mixture obtained by making plant-derived lecithin and serine react in presence of phospholipase D as an active ingredient.
The agent of the present invention reduces the isoplastane concentration in the body, for example, blood, urine, saliva, tears, semen, particularly blood and urine isoplastane concentrations.

(1) Glycerophospholipid In the first isoplastane- lowering agent of the present invention, when the glycerophospholipid is a mixture of PS and PI, the weight ratio of PS and PI is converted to dry weight and converted to PS. : PI is preferably about 0.5-20: 1, more preferably about 1-10: 1, and even more preferably about 1-4: 1.
PS is commercially available from SIGMA, BIOMOL, NOF Corporation and others. PI is commercially available from BIOMOL. A mixture of PS and PI can be prepared by mixing these commercially available products.
PI can be isolated from lecithin derived from plants such as soybean, rapeseed, sunflower, and palm. PI is also SLP-WHITE (phosphatidylcholine (hereinafter also abbreviated as “PC”) 25.6% by weight, phosphatidylethanolamine (hereinafter also abbreviated as “PE”) 24.1% by weight, phosphatidine Acid (hereinafter may be abbreviated as “PA”) 8% by weight, PI weight 12%, other approximately 30% by weight), SLP-PI powder (PC18% by weight, PE22% by weight, PA8% by weight, PI weight) It can also be isolated from commercially available lecithin such as 17% and about 35% by weight. PI can be isolated by various types of chromatography.

  In addition, since the above raw material lecithin (plant-derived lecithin and commercially available lecithin) contains PC and PE, serine and phospholipase D (hereinafter sometimes abbreviated as PLD) are allowed to act on these lecithins for base exchange. Thus, a glycerophospholipid mixture containing PS can be obtained. Further, when the raw material lecithin further contains PI, a glycerophospholipid mixture containing PS and PI can be obtained. The glycerophospholipid mixture containing PS can be used as an active ingredient of the first isoplastane lowering agent of the present invention, and the glycerophospholipid mixture containing PS and PI is the first and second isoplastane lowering agent of the present invention. It can be used as an active ingredient. PI and PS can also be formulated in a state in which other contaminants such as glycerophospholipid are included. Moreover, PS or PI can also be isolated from these glycerophospholipid mixtures.

  The glycerophospholipid mixture in which the weight ratio of PS to PI (in terms of dry weight) is PS: PI = about 0.5 to 20: 1 is the ratio of the total weight of PC and PE to PI weight as lecithin as the starting material ( (PC + PE) / PI) can be obtained by carrying out the above base exchange reaction using about 25% by weight in terms of dry weight. The plant-derived lecithin and the commercially available lecithin usually contain PC, PE, and PI in this range, but when the content of PC and PE is small, for example, a high-purity phospholipid such as SLPC55 (manufactured by Sumi Oil) is used. By adding, the ratio of the total weight of PC and PE to the PI weight in lecithin ((PC + PE) / PI) (in terms of dry weight) may be adjusted to about 25% by weight.

The base exchange reaction of lecithin can be performed, for example, by the method described in JP-A-2007-014270.
That is, before performing the base exchange reaction, lecithin may be stirred in a two-phase system composed of an organic solvent phase and an aqueous phase. The organic solvent is not particularly limited, and known solvents such as aliphatic hydrocarbons, cycloaliphatic hydrocarbons, halogenated hydrocarbons, esters, ethers, and ketones may be used. A buffer solution is preferred as the aqueous phase. The total concentration of acids, bases and salts in the buffer is preferably about 0.1-2M. In the two-phase system, water is preferably 20% by weight or less based on the organic solvent. Stirring in the two-layer system may be performed at a temperature of about 10 to 40 ° C. for about 30 minutes to 2 hours. This usually forms an emulsion of glycerophospholipid, organic solvent and water.
Next, serine and PLD are added to the mixture, and the concentration of glycerophospholipid in the base exchange reaction system is preferably about 5 to 40% by weight. The concentration of serine in this reaction system is preferably about 20 to 40% by weight.

Phospholipase D is not particularly limited, and phospholipase D manufactured by Nagase ChemteX, phospholipase D derived from Streptomyces chromofuscus manufactured by Sigma, phospholipase D derived from Streptomyces sp., And the like can be used. The concentration of phospholipase D in this reaction system may be about 5 to 200 U with respect to 1 g of glycerophospholipid. In addition, 1U uses 95% soybean phosphatidylcholine as a substrate, and reacts 0.2M acetic acid buffer solution (pH 4.0, 10 mM CaCl ₂ , 1.3% Triton X-100) at 37 ° C with a substrate concentration of 0.16%. The amount of enzyme that releases 1 μmol of choline per minute.
The base exchange reaction may be performed under a pH condition of about 3.5 to 10 and a temperature of about 10 to 40 ° C. for about 1 to 72 hours.

By the base exchange reaction, PS reacts with PC, PE, etc. in glycerophospholipid and serine. Since PI hardly reacts with the hydroxyl group-containing compound in the base exchange reaction, PI contained in the raw material glycerophospholipid is almost directly contained in the phospholipid mixture after the base exchange reaction.
The base exchange reaction may be terminated by inactivating PLD by heating. Furthermore, after obtaining an organic solvent phase by a centrifugal method or the like, the reaction mixture may be concentrated by removing the organic solvent under reduced pressure.
Next, crystallization is performed with acetone or ethanol, a solid is obtained by solid-liquid separation, and dried, whereby a glycerophospholipid mixture containing PS and PI can be isolated.

(2) Formulation The agent of the present invention includes pharmaceuticals, quasi drugs, food compositions and the like.

Orally Administered As a dosage form when the isoplastane reducing agent of the present invention is a pharmaceutical, a typical example is an orally administered preparation. Examples of solid preparations for oral administration include powders, granules, tablets, tablets, pills, capsules, chewables, and the like, and examples of liquid preparations include emulsions, liquids, syrups and the like. Among these, granules, tablets, tablets, and capsules are preferable, and granules are more preferable because they are easy to take and have a good taste.

  The solid preparation is prepared by blending a pharmaceutically acceptable carrier or additive with glycerophospholipid which is an active ingredient or a mixture thereof. For example, excipients such as sucrose, lactose, glucose, starch, mannitol; binders such as gum arabic, gelatin, crystalline cellulose, hydroxypropylcellulose, methylcellulose; disintegrants such as carmellose and starch; anhydrous citric acid Stabilizers such as sodium laurate and glycerol are blended. Further, it may be coated or encapsulated with gelatin, white sugar, gum arabic, carnauba wax or the like. The liquid preparation is prepared, for example, by dissolving or dispersing the above active ingredient in water, ethanol, glycerin, simple syrup, or a mixture thereof. In these preparations, additives such as sweeteners, preservatives, demulcents, lubricants, diluents, buffers, flavoring agents, and coloring agents may be added.

The content of glycerophospholipid or glycerophospholipid mixture in the orally administered agent is as follows.
That is, when the active ingredient is PS or PI, the content of PS or PI is preferably about 0.005 to 20% by weight in terms of dry weight, and about 0.01 to 15% with respect to the entire preparation. More preferably, it is wt%, and even more preferably about 0.01-10 wt%. In addition, when the active ingredient is PS and PI, the total content of PS and PI is preferably about 0.001 to 20% by weight with respect to the entire preparation in terms of dry weight, about 0.005 to More preferably, it is 15% by weight, and even more preferably about 0.01-10% by weight.

Further, in the case of the second isoplastane reducing agent of the present invention, the total content of PS and PI contained in the glycerophospholipid mixture obtained by the reaction of plant-derived lecithin, serine and phospholipase D is in the whole preparation. On the other hand, in terms of dry weight, it is preferably about 0.001 to 20% by weight, more preferably about 0.005 to 15% by weight, and still more preferably about 0.01 to 10% by weight.
If it is the said range, sufficient isoplastane density | concentration reduction | decrease effect | action will be acquired by administration of a suitable quantity.

Other dosage forms In addition, when the isoplastane reducing agent of the present invention is a pharmaceutical, it can be made into dosage forms such as injections and suppositories.
An injection can be obtained by dissolving or dispersing glycerophospholipid or a glycerophospholipid mixture in distilled water for injection or physiological saline. Moreover, a water-soluble inorganic acid or a salt thereof, a water-soluble organic acid or a salt thereof, a neutral amino acid, an acidic amino acid or a salt thereof, a salt of a basic amino acid, or the like may be contained as a pH adjuster or the like. Further, a buffer, a stabilizer, a soothing agent, a preservative, and the like may be contained.
The content of glycerophospholipid or glycerophospholipid mixture in the injection is as follows. That is, when the active ingredient is PS or PI, the content of PS or PI is preferably about 0.005 to 2.5% by weight in terms of dry weight, and about 0.05 to 1 More preferably, it is wt%, and even more preferably about 0.1-0.5 wt%. Further, when the active ingredient is PS and PI, the total content of PS and PI is preferably about 0.002 to 2.5% by weight with respect to the whole preparation in terms of dry weight, about 0.02 to More preferred is 1% by weight, and even more preferred is about 0.08 to 0.5% by weight.

Further, in the case of the second isoplastane reducing agent of the present invention, the total content of PS and PI contained in the glycerophospholipid mixture obtained by the reaction of plant-derived lecithin, serine and phospholipase D is in the whole preparation. On the other hand, in terms of dry weight, it is preferably about 0.002 to 2.5% by weight, more preferably about 0.02 to 1% by weight, and still more preferably about 0.08 to 0.5% by weight.
If it is the said range, sufficient isoplastane density | concentration reduction | decrease effect is acquired by use of a suitable quantity.

Suppositories include glycerophospholipids, acrylic polymers such as carbopol and polycarbophil; cellulosic polymers such as hydroxypropylcellulose and hydroxypropylmethylcellulose; natural polymers such as sodium alginate and chitosan; fatty acid waxes It can prepare by mix | blending with bases, such as. Further, a preservative such as sodium benzoate, potassium sorbate and paraben; a pH regulator such as hydrochloric acid, citric acid and sodium hydroxide; and a stabilizer such as methionine may be added.
The content of glycerophospholipid or glycerophospholipid mixture in the suppository is as follows. That is, when the active ingredient is PS or PI, the content of PS or PI is preferably about 0.1 to 5% by weight in terms of dry weight, and about 0.2 to 3% with respect to the whole preparation. More preferred is wt%, and even more preferred is about 0.8-2 wt%. In addition, when the active ingredient is PS and PI, the total content of PS and PI is preferably about 0.05 to 5% by weight with respect to the entire preparation in terms of dry weight, about 0.1 to More preferably 3% by weight, even more preferably about 0.5-2% by weight.

Further, in the case of the second isoplastane reducing agent of the present invention, the total content of PS and PI contained in the glycerophospholipid mixture obtained by the reaction of plant-derived lecithin, serine and phospholipase D is in the whole preparation. On the other hand, in terms of dry weight, it is preferably about 0.05 to 5% by weight, more preferably about 0.1 to 3% by weight, and still more preferably about 0.5 to 2% by weight.
If it is the said range, sufficient isoplastane density | concentration reduction | decrease effect is acquired by use of a suitable quantity.

Food Composition When the isoplastane reducing agent of the present invention is a food composition, the content of the glycerophospholipid of the present invention in the composition is preferably about 0.02 to 30% by weight, and about 0.05 to 20% by weight. % Is more preferable. If it is the said range, the glycerophospholipid which can fully reduce | isolate the body isoplastane density | concentration will be contained in the amount of foods which can be ingested reasonably.

This food composition is suitable for use as a health food (supplement). Moreover, it is suitable for health functional foods (food for specified health use, nutritional functional food).
This food composition is blended with excipients or additives usually used in foods, tablets, tablets, pills, granules, powders, powders, capsules, wettable powders, emulsions, liquids, extracts. Or a dosage form such as an elixir. Among these, tablets, tablets, and granules are preferable, and granules are more preferable because they are easy to take and have a good taste.
Common excipients used in food include syrup, gum arabic, sucrose, lactose, powdered reduced maltose, cellulose sugar, mannitol, maltitol, dextran, starches, gelatin, sorbit, tragacanth, polyvinylpyrrolidone Agents; sucrose fatty acid esters, glycerin fatty acid esters, magnesium stearate, calcium stearate, talc, polyethylene glycol, etc .; disintegrants such as potato starch; wetting agents such as sodium lauryl sulfate. Examples of additives include fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, and the like.

  In addition, this food composition includes beverages (sports drinks, drinks, milk drinks, lactic acid bacteria drinks, fruit juice drinks, carbonated drinks, vegetable drinks, tea drinks, etc.), confectionery (baked confectionery such as cookies, jelly, gum, gummi , Etc.). Among these, milk drinks are preferable in terms of formulation and compatibility with phospholipids and ease of formulation adjustment.

(3) How to use
The amount of the isoplastane reducing agent of the present invention varies depending on the health condition and age of the subject, but is generally as follows. That is, in the case of an oral administration agent, the dose of PS or PI is preferably about 0.02 to 1.5 g per day in terms of dry weight. When the orally administered agent contains PS and PI, the total dose of PS and PI is preferably about 0.01 to 1.5 g per day in terms of dry weight. In the case of the second isoplastane-lowering agent of the present invention, the glycerophospholipid mixture may be administered in such an amount that the total dose of PS and PI is about 0.01 to 1.5 g per day in terms of dry weight. preferable.
In the case of an injection, the dose of PS or PI is preferably about 0.01 to 100 mg per day in terms of dry weight. When the orally administered preparation contains PS and PI, the total dose of PS and PI is preferably about 0.005 to 100 mg per day in terms of dry weight. In the case of the second isoplastane-lowering agent of the present invention, it is preferable to administer a glycerophospholipid mixture in an amount such that the total dose of PS and PI is about 0.005 to 100 mg per day in terms of dry weight. .

  Moreover, when it is a suppository, it is preferable that the dosage of PS or PI is about 0.01-100 mg per day in terms of dry weight. When the oral administration agent contains PS and PI, the total dose of PS and PI is preferably about 0.005 to 100 mg per day in terms of dry weight. In the case of the second isoplastane lowering agent of the present invention, it is preferable to administer a glycerophospholipid mixture in an amount that the total dose of PS and PI is about 0.005 to 100 mg per day in terms of dry weight. .

Food composition When the isoplastane reducing agent of the present invention is a food composition, the intake varies depending on the body weight, health status, age, etc. of the intake person, but the daily intake of PS or PI is the dry weight. It is preferably about 0.02 to 1.5 g in terms of. When this food composition contains PS and PI, the total intake of PS and PI is preferably about 0.01 to 1.5 g per day in terms of dry weight.

Use object Use object is not particularly limited, but a person having a high isoplastane concentration in the body, for example, blood or urine can be a suitable object. Specifically, people with renal dysfunction, those who have metabolic syndrome such as obesity, hyperglycemia, hypertension, lipid abnormalities, elderly people, those who feel tired, fatigue due to exercise etc. A person who is fatigued or physically fatigued (especially a person who has accumulated fatigue) is a suitable target.
The present invention also includes a method for reducing the concentration of isoplastane in the body, wherein the glycerophospholipid or glycerophospholipid mixture described above is administered to a mammal, particularly a human.

(II) Renal function improving agent / fatigue improving agent The renal function improving agent and fatigue improving agent of the present invention contain the above-described glycerophospholipid or glycerophospholipid mixture as an active ingredient. The renal function improving agent and fatigue improving agent of the present invention include pharmaceuticals, quasi drugs, food compositions and the like. Other configurations are as described for the isoplastane reducing agent.
The present invention also includes a method for improving renal function and a method for improving fatigue, in which the above-described glycerophospholipid or glycerophospholipid mixture is administered to mammals, particularly humans.
In the present invention, “improvement” includes symptom relief, cure, prevention (suppression of onset, suppression of symptom progression, etc.) and the like.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.
Production Example 1 (Production of PI / PS-containing phospholipid mixture)
7 g of soybean lecithin (UltralecP (ADM)) was mixed with 70 mL of a heptane / acetone mixed solution (heptane: acetone = 4: 1) and dissolved to obtain a lecithin solution. Separately, an enzyme-containing serine solution containing 20 g of serine and 500 U of PLD (manufactured by Nagase ChemteX) in 67 mL of 1M acetate buffer (pH 4.5) was prepared.
The enzyme-containing serine solution was added to the lecithin solution and stirred at 30 ° C. for 5 hours. Next, 75 mL of the above heptane / acetone mixture and 20 g of sodium chloride were added to this mixture, and the mixture was stirred for 1 hour and allowed to stand to separate the aqueous phase and the organic solvent phase, and then the organic phase was recovered. An organic solvent solution containing PI and PS was obtained. This organic solvent solution contained 8 g of solids (glycerophospholipid mixture).
It was as follows when the composition of the solid content was investigated by HPLC of the following conditions. PS 32 wt%, PI 21 wt%, PC 2 wt%, PE 9 wt%, PA 13 wt%.

<HPLC conditions>
Column used: GL Sciences Unisil Q NH ₂ (4.6mm ID x 250mm)
Mobile phase: acetonitrile / methanol / 50 mM ammonium dihydrogen phosphate = 1856/874/270
Flow rate: 1.3mL / min Detection: UV 205nm

Production Example 2 (Production of PS-containing phospholipid mixture)
A PS-containing organic solvent solution was obtained in the same manner as in Production Example 1 except that Lipoid S100 (Lipoid) was used as soybean lecithin. This organic solvent solution contained 8 g of solids (glycerophospholipid mixture). The composition was examined by the same method as in Production Example 1 and was as follows. PS 93 wt%, PC 0.5 wt%, PA 4 wt%.

その後、エーテル麻酔下腹部大動脈から採血し、血清を得、イソプラスタン濃度をELISA（Cayman）で定量した。結果を図１に示す。
PI・PS含有リン脂質を投与した群(製造例１群)、及びPS含有リン脂質を投与した群(製造例２群)共に、対照群に比し、血中イソプラスタン濃度が有意に低かった（Bartlettの分散検定後、Dunnnett法で統計解析。p < 0.05）。 [Example 1]
(Blood isoplastane lowering effect on obese rats)
Zucker rats (control group n = 5) were given AIN76 modified diet (Oriental Yeast Co., Ltd.) having the composition shown in Table 1 below for 4 weeks, and Zucker rats (Manufacturing Example 1 group n = 5) in Table 1 below. AIN76 modified diet containing 2% PI / PS-containing phospholipids (manufactured by the same company) was given for 4 weeks, and PI / PS-containing phospholipids or PSs whose composition is shown in Table 1 below were given to Zucker rats (Production Example 2 group n = 6) AIN76 modified diet (manufactured by the company) containing 2% of phospholipids contained was supplied for 4 weeks.

Thereafter, blood was collected from the abdominal aorta under ether anesthesia to obtain serum, and the isoplastane concentration was quantified by ELISA (Cayman). The results are shown in FIG.
Both the group administered with PI / PS-containing phospholipids (Production Example 1 group) and the group administered with PS-containing phospholipids (Production Example 2 group) had significantly lower blood isoplastane concentrations than the control group. (After Bartlett's variance test, statistical analysis by Dunnett method, p <0.05).

[Example 2]
(Urine isoplastane lowering effect on obese people)
Nine men with a BMI of 23 to 30 were given a granule preparation containing 400 mg of the PI / PS-containing phospholipid mixture of Production Example 1 once a day for 8 weeks. Urine before and after taking was collected, and the isoplastane concentration was quantified by ELISA (Cayman).
The results are shown in FIG. The isoplastane concentration in the figure is the correction value (ng / mg CRE) obtained by dividing the measured value of isoplastane concentration by the urinary creatinine concentration (mg / mL) to correct the effect of urine concentration. It is. The solid line shows the average of 9 people.
It can be seen that by taking PI / PS-containing phospholipid, the isoplastane concentration was significantly reduced. (Statistical analysis with Paired t-test, p <0.01).

牛乳に製造例１と同様にして得られたPI・PS含有リン脂質混合物を混合し、室温で2分間、5000rpmでTKホモミクサーで攪拌した。乳化後、100℃、10分加熱処理した。 Formulation example

The PI / PS-containing phospholipid mixture obtained in the same manner as in Production Example 1 was mixed with milk and stirred with a TK homomixer at 5000 rpm for 2 minutes at room temperature. After emulsification, heat treatment was performed at 100 ° C. for 10 minutes.

豆乳に上記組成を混合し、室温で2分間、5000rpmでTKホモミキサーで攪拌した。乳化後、100℃、10分加熱処理した。PI・PS含有リン脂質混合物は、製造例１と同様にして調製したものである。

The above composition was mixed with soy milk and stirred with a TK homomixer at 5000 rpm for 2 minutes at room temperature. After emulsification, heat treatment was performed at 100 ° C. for 10 minutes. The PI / PS-containing phospholipid mixture was prepared in the same manner as in Production Example 1.

上記の全ての成分を室温にて混合および撹拌して均一な溶液として、飲料を作製する。PI・PS含有リン脂質混合物は、製造例１と同様にして調製したものである。

All the above ingredients are mixed and stirred at room temperature to produce a beverage as a uniform solution. The PI / PS-containing phospholipid mixture was prepared in the same manner as in Production Example 1.

PI・PS含有リン脂質混合物、乳糖、ジャガイモデンプンを均一に混合する。混合物にポリビニルアルコールの水溶液を加え、湿式顆粒造粒法により顆粒を調製する。顆粒を乾燥し、ステアリン酸マグネシウムを混合し、圧縮打錠して重量300mgの錠剤を作製する。PI・PS含有リン脂質混合物は、製造例１と同様にして調製したものである。

Mix PI / PS-containing phospholipid mixture, lactose, and potato starch evenly. An aqueous solution of polyvinyl alcohol is added to the mixture, and granules are prepared by wet granulation. The granules are dried, mixed with magnesium stearate and compressed into tablets with a weight of 300 mg. The PI / PS-containing phospholipid mixture was prepared in the same manner as in Production Example 1.

  According to the agent of the present invention, the concentration of isoplastane in the body can be effectively reduced, thereby typically improving renal function, and metabolic syndrome, aging symptoms, fatigue symptoms Etc. can be improved. Therefore, the agent of the present invention can be suitably used as a health food such as a pharmaceutical, a quasi-drug, and a health functional food.

Claims (8)

  An isoplastane lowering agent comprising at least one glycerophospholipid selected from the group consisting of phosphatidylserine and phosphatidylinositol.   The isoplastane lowering agent according to claim 1, wherein the glycerophospholipids are phosphatidylserine and phosphatidylinositol.   The isoplastane reducing agent according to claim 2, wherein the weight ratio of phosphatidylserine and phosphatidylinositol is phosphatidylserine: phosphatidylinositol = 0.5 to 20: 1 in terms of dry weight.   An isoplastane reducing agent comprising a glycerophospholipid mixture obtained by reacting plant-derived lecithin and serine in the presence of phospholipase D.   A renal function improving agent comprising at least one glycerophospholipid selected from the group consisting of phosphatidylserine and phosphatidylinositol.   The renal function improving agent according to claim 5, wherein the glycerophospholipids are phosphatidylserine and phosphatidylinositol.   The renal function improving agent according to claim 6, wherein the weight ratio of phosphatidylserine and phosphatidylinositol is phosphatidylserine: phosphatidylinositol = 0.5 to 20: 1 in terms of dry weight.   A renal function improving agent comprising a glycerophospholipid mixture obtained by reacting plant-derived lecithin and serine in the presence of phospholipase D.

Images