JP4742489B2 - Composition for preventing or improving hypertriglyceridemia - Google Patents

Description

【００１７】
高脂血症惹起群はさらに対照群とプロリン投与群の２群に分けた。正常群および対照群には水をプロリン投与群には市販のプロリンを１０００ｍｇ／ｋｇの用量で１日１回１４日間連日経口投与した。最終投与翌日にエーテル麻酔下で後大静脈から採血し、直ちに血清を分離した。
【００１８】
得られた血清中のトリグリセライド（ＴＧと略記）および総コレステロール（Ｔ−Ｃｈｏと略記）濃度は和光純薬工業製の各測定キット（トリグリセライドＧ−テストワコー、コレステロールＣ2−テストワコー）を用いて定量した。
【００１９】
結果
ハムスターに高脂肪・高コレステロール食を１５日間連日摂取させると、正常食摂取群に比較して血清中のＴＧおよびＴ−Ｃｈｏが有意に増加し、高脂血症が惹起された（図１、２）。プロリン１０００ｍｇ／ｋｇ投与群には、この血清ＴＧ上昇を抑制する作用が認められた（図１）一方、Ｔ−Ｃｈｏの上昇には影響を及ぼさなかった（図２）。
また、飼育期間中にプロリン投与群において、体重の減少も認められなかった。さらに解剖所見からもプロリン投与による毒性は確認されなかった。
以上の結果から、プロリンは長期投与でも安全性が高く、高トリグリセライド血症に対して予防あるいは改善作用を有することが明らかになった。
【図面の簡単な説明】
【図１】正常群、高脂血症惹起群及び高脂血症惹起群にプロリン１０００ｍｇ／ｋｇ投与群の血清中トリグリセライド濃度を示したものである。##は高脂血症惹起群が正常群に対してp<0.01の有意差を示す。*はプロリン投与群が対照群に対してp<0.05の有意差を示す。
【図２】正常群、高脂血症惹起群及び高脂血症惹起群にプロリン１０００ｍｇ／ｋｇ投与群の血清中総コレステロール濃度を示したものである。##は高脂血症惹起群が正常群に対してp<0.01の有意差を示す。*はプロリン投与群が対照群に対してp<0.05の有意差を示す。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a composition for preventing or ameliorating hypertriglyceridemia that is safe even after long-term use.
[0002]
[Prior art]
In recent years, lifestyle-related diseases, for which lifestyle habits such as eating habits, exercise habits, rest, smoking, and alcohol consumption are thought to affect the onset and progression of the disease, have attracted attention. In particular, in advanced countries, hyperlipidemia, obesity, non-insulin-dependent diabetes (type 2 diabetes), hypertension, and the like, which are highly related to dietary habits and exercise habits, are increasing. As a result, it has become a major social problem not only in the health of the people in those countries, causing a drop in quality of life (QOL) but also causing a rapid increase in medical costs. .
[0003]
Hyperlipidemia is a condition in which lipids in the blood increase. For the diagnosis, serum cholesterol and triglyceride are used as general indicators. Hyperlipidemia is further classified into hypercholesterolemia in which only serum cholesterol increases and hypertriglyceridemia in which only triglyceride increases.
[0004]
Cholesterol is used in the body as a constituent of cell membranes and as a raw material for certain hormones, and an increase in serum cholesterol does not all have an adverse effect on the body. Cholesterol is present in the blood in a form bound to lipoproteins. This lipoprotein is classified into chylomicron, VLDL, LDL, and HDL depending on the specific gravity. Of particular concern in hypercholesterolemia is an increase in LDL. An increase in LDL is said to cause arteriosclerosis and heart disease. In addition, a recent report also reports that people with higher cholesterol levels live longer, and there are documents that warn overdose of foods that have been designed to lower cholesterol levels (Pharmacia, Vol. 37, No. 9, 2001). This may be related to the use of cholesterol as a constituent of biological membranes and as a raw material for hormones.
[0005]
On the other hand, triglyceride is important as an energy source for animal activity and is absorbed from the diet or synthesized in the body. Excess triglyceride accumulates as fat around the viscera and subcutaneously and induces obesity. This may also promote type 2 diabetes and hypertension. Moreover, the correlation with hypertriglyceridemia has also been clarified from the relation with arteriosclerosis. In recent years, in view of dietary habits and exercise habits that have attracted particular attention in lifestyle habits, that is, drugs that regulate blood triglyceride concentration are useful in view of overeating and lack of exercise.
[0006]
Until now, an anti-obesity agent containing a plurality of amino acids including proline has been disclosed (Patent Document 1). However, this anti-obesity agent is composed of 11 kinds of amino acids in addition to proline. In the prior art, the combination of the above amino acids reduces blood cholesterol and increases blood triglyceride concentration.However, when proline is administered alone, the present invention reduces blood triglyceride concentration and increases blood triglyceride concentration. It is characterized by having no effect on cholesterol and is essentially different from the present invention.
[Patent Document 1]
JP-A-6-24977 [Problems to be Solved by the Invention]
The object of the present invention is to provide a composition for safely and effectively treating or preventing hypertriglycerideemia caused by lifestyle habits, particularly eating habits.
[0007]
[Means for Solving the Problems]
As a result of intensive studies aimed at solving the above problems, the present inventors have found that proline significantly suppresses an increase in serum triglyceride concentration derived from lifestyle habits, particularly eating habits, and completed the present invention.
[0008]
That is, the present invention is (1) a composition for preventing or improving hypertriglyceridemia, characterized by containing proline, and (2) a composition according to the above (1), wherein the cause of hypertriglyceridemia is lifestyle habits. And (3) The composition according to (1) above, wherein the cause of hypertriglyceridemia is eating habits.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
A commercially available proline can be used in the present invention. Proline is one of the amino acids constituting the body, and is known to be used in the body as a raw material for hydroxyproline, which is a major component of the skin. Proline is abundant in cereals such as barley, wheat and hatomugi, processed soy foods, fish and meat, and is safe even when ingested for a long time.
[0010]
The effective dose of proline in the present invention can be appropriately increased or decreased in consideration of age, sex, etc., but is usually 10 mg to 5000 mg per day for adults, preferably 100 mg to 3000 mg. This is because when the amount is less than 10 mg, the effect of the present invention is not recognized, and even when the dose is more than 5000 mg, no further effect can be expected.
[0011]
The proline used in the present invention is safe even when administered for a long time. When hamsters were orally administered once daily for 14 days at doses of 300, 1000 and 3000 mg / kg, no toxicity was observed.
[0012]
The present invention can be used for pharmaceuticals, quasi drugs or foods. The present invention also provides vitamins, xanthine derivatives, herbal medicines, natural products, excipients, pH adjusting agents, cooling agents, suspending agents, antifoaming agents within the qualitative and quantitative ranges that do not impair the effects of the invention. , Mixing thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, surfactants, plasticizers, perfumes, etc. Oral or parenteral preparations such as liquids, tablets, granules, powders, capsules, dry syrups, chewable tablets and transmucosal agents can be used.
[0013]
【The invention's effect】
According to the present invention, hyperlipidemia, particularly hypertriglyceridemia, can be prevented or improved, and a highly safe drug or food can be provided.
[0014]
【Example】
The present invention will be specifically described below with reference to examples and test examples.
Example 1
(Ingredient) Blending amount Proline 50g
Lactose 5g
Corn starch 2.45g
Magnesium aluminate metasilicate 0.35g
Light silicic acid 0.4g
Low substituted hydroxypropylcellulose 0.5g
After mixing the above components, an appropriate amount of purified water was added and kneaded, granulated and dried to obtain a granular material. To this granulated product, magnesium stearate, hydrogenated oil and flavor were appropriately added and tableted to prepare 100 tablets.
Example 2
10 g of aspartame was further added to Example 1 to obtain a granulated product in the same manner. Magnesium stearate and hydrogenated castor oil were appropriately added to this granulated product and mixed uniformly to prepare 100 sachets.
Example 3
(Ingredient) Blending amount Proline 20g
Low molecular weight sodium alginate 80g
Fructose 20g
Benzoic acid 2g
Citric acid 7g
Sodium malate 15g
10g polyoxyethylene hydrogenated castor oil
Distilled water was added to the above components to make a 3 L solution.
Example 4
(Ingredient) Blending amount Proline 20g
Cholestyramine 80g
Fructose 20g
Benzoic acid 2g
Citric acid 7g
Sodium malate 15g
10g polyoxyethylene hydrogenated castor oil
Distilled water was added to the above components to make a 3 L solution.
[0015]
Test example 1
The purpose of this study is to verify the pharmacological effects of proline on hyperlipidemia caused by lifestyle habits, especially eating habits.
In the present invention, LVG (SYR) BR male hamster (Syrian hamster) [3 weeks old] was used. After pre-feeding for about one week until use in the experiment, it was divided into two groups: a normal diet intake group (normal group) and a high fat / high cholesterol diet intake group (hyperlipidemia-induced group). The normal group and the hyperlipidemia-inducing group were each given a normal diet or a high fat / high cholesterol diet having the composition shown in Table 1 for 15 days.
[0016]
[Table 1]
Ingredient composition

[0017]
The hyperlipidemia-inducing group was further divided into two groups: a control group and a proline administration group. The normal group and the control group were orally administered with water and the proline-administered group with commercially available proline at a dose of 1000 mg / kg once a day for 14 days. The day after the final administration, blood was collected from the posterior vena cava under ether anesthesia, and the serum was immediately separated.
[0018]
The triglyceride (abbreviated as TG) and total cholesterol (abbreviated as T-Cho) concentrations in the obtained serum were quantified using each measurement kit (Triglyceride G-Test Wako, Cholesterol C2-Test Wako) manufactured by Wako Pure Chemical Industries, Ltd. did.
[0019]
Results When a hamster was ingested with a high-fat / high-cholesterol diet for 15 days, serum TG and T-Cho were significantly increased as compared with the normal diet group, and hyperlipidemia was induced (FIG. 1). 2). The proline 1000 mg / kg administration group was found to have an effect of suppressing this increase in serum TG (FIG. 1), while it did not affect the increase in T-Cho (FIG. 2).
In addition, no decrease in body weight was observed in the proline administration group during the breeding period. Furthermore, no toxicity from proline administration was confirmed from the anatomical findings.
From the above results, it was revealed that proline is highly safe even after long-term administration and has a preventive or ameliorating action on hypertriglyceridemia.
[Brief description of the drawings]
FIG. 1 shows serum triglyceride concentrations in a proline 1000 mg / kg administration group in a normal group, a hyperlipidemia-induced group, and a hyperlipidemia-induced group. ## indicates a significant difference of p <0.01 in the hyperlipidemia-induced group compared to the normal group. * Indicates a significant difference of p <0.05 in the proline-administered group relative to the control group.
FIG. 2 shows the serum total cholesterol concentration of a proline 1000 mg / kg administration group in a normal group, a hyperlipidemia-induced group, and a hyperlipidemia-induced group. ## indicates a significant difference of p <0.01 in the hyperlipidemia-induced group compared to the normal group. * Indicates a significant difference of p <0.05 in the proline-administered group relative to the control group.

Claims (3)

A composition for preventing or improving hypertriglyceridemia , comprising proline as an active ingredient . The composition according to claim 1, wherein the cause of hypertriglyceridemia is lifestyle habits. The composition according to claim 1, wherein the cause of hypertriglyceridemia is eating habits.

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