JP4465963B2 - Composition for preventing or improving hyperlipidemia - Google Patents

Description

（結果）
【００２４】
（図１）、（図２）及び（図３）に示したごとく、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ＮＥＦＡ、Ｔ−Ｃｈｏが有意に増加し、高脂血症が惹起された。Ｌ−プロリン３００ｍｇ／ｋｇ投与群及びムイラプアマエキス５００ｍｇ／ｋｇ投与群は血清中ＴＧ、ＮＥＦＡ、Ｔ−Ｃｈｏに影響を及ぼさなかったが、Ｌ−プロリン３００ｍｇ／ｋｇとムイラプアマエキス５００ｍｇ／ｋｇの併用群においては、血清ＴＧ、ＮＥＦＡ、Ｔ−ｃｈｏの上昇を抑制した。
安全性について確認したところ、投与期間中にラットの異常行動も見られず、また、順調に体重も増加した。解剖時にも異常な所見は認められなかった。
以上の結果から、Ｌ−プロリンとムイラプアマエキスの併用投与は、高脂血症に対して予防あるいは改善作用を有し、安全性にも問題ないことが明らかになった。
【図面の簡単な説明】
【図１】実験に用いたラットの血清中トリグリセライド濃度を示したものである。
【図２】実験に用いたラットの血清中遊離脂肪酸濃度を示したものである。
【図３】実験に用いたラットの総コレステロール濃度を示したものである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a composition for preventing or improving hyperlipidemia that is safe without side effects, and a pharmaceutical, quasi-drug or food containing the same.
[0002]
[Prior art]
At present, an increasing number of people become obese due to lifestyle habits such as lack of exercise and overeating. This obesity is closely associated with hyperlipidemia. Hyperlipidemia is also correlated with hypertension and diabetes. Hyperlipidemia, diabetes, and high blood pressure are considered to cause serious diseases such as heart disease and arteriosclerosis.
[0003]
Hyperlipidemia is a disease that results in an increase in lipid concentration in the blood. With the recent westernization of food culture, the intake of fat has increased, so the number of patients with hyperlipidemia has also increased. Hyperlipidemia is one of the risk factors for arteriosclerosis.
[0004]
In order to treat this hyperlipidemia, there are methods such as administration of pharmaceuticals in addition to methods of exercise therapy and diet restriction. With regard to dietary restrictions, the content and quantity of conventional meals are limited, and the stress that patients receive is extremely heavy and burdensome. The use of appetite suppressants and lipid substitutes can also be considered, but there are concerns about safety and effectiveness. Furthermore, there is a problem in continuing exercise therapy considering modern society.
[0005]
Under such circumstances, the development of pharmaceuticals, quasi-drugs or foods that prevent or ameliorate safe hyperlipidemia without side effects has been expected.
[0006]
Thus, the inventors have found that taking a composition of L-proline, which is one of amino acids, and muirapuama, suppresses an increase in blood cholesterol concentration, triglyceride concentration, and free fatty acid concentration. Hyperlipidemia is diagnosed using these blood lipid concentrations as an index, and it is very useful to effectively suppress the blood lipid concentration.
[0007]
Prior to the present invention, L-proline has also been found to suppress an increase in blood triglyceride concentration (Patent Document 1). However, this technique requires L-proline to be administered at 1000 mg / kg, and it has to be administered more in comparison with the 300 mg / kg of the present invention.
[Patent Document 1]
Japanese Patent Application 2002-198322
[0008]
[Problems to be solved by the invention]
An object of the present invention is to provide a composition useful for the prevention or treatment of hyperlipidemia that is safe and effective without side effects.
[0009]
[Means for Solving the Problems]
As a result of intensive studies for the purpose of solving the above-mentioned problems, the present inventors have used muirapuama in combination with L-proline alone even at a low concentration (300 mg / kg) that is not effective. It was found that not only the serum triglyceride concentration but also the increase in serum cholesterol concentration and free fatty acid concentration were suppressed.
[0010]
That is, it was found that the combined use of L-proline and muirapuama was effective in preventing or improving hyperlipidemia, and the present invention was completed.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
The present invention is effective in preventing or improving hyperlipidemia. Furthermore, obesity can be prevented or improved by improving hyperlipidemia.
[0012]
L-proline used in the present invention is one of 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.
[0013]
The effective dose of L-proline 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.
[0014]
The base plant of the muilapuama used in the present invention belongs to the Olacaceae family that grows in the Amazon basin of Brazil, and includes Ptychopetalum uncinatum, Liriosma ovata, and the like, preferably Ptychopetalum olacoides, in addition to Ptychopetalum olacoides. In the present invention, the roots of these base plants are used.
[0015]
The muirapuama used in the present invention can use extracts as well as herbal medicines. Here, the extract includes any form such as a herbal extract, a concentrated extract, and a dry extract. The extract can be produced by an ordinary method using water, alcohol (methanol, ethanol, propanol, isopropanol, etc.), ethyl acetate, acetone, a mixed solution thereof or the like as an extraction solvent.
[0016]
Muirapuama used in the present invention is a herbal medicine that has been used for a long time in folk remedies, so its safety is ensured. Therefore, continuous administration over a long period is possible.
[0017]
The effective dose of muirapuama 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 as an active ingredient equivalent, and preferably 100 mg to 3000 mg for adults.
[0018]
The blending ratio of the combination of L-proline and muirapuama is not particularly limited as long as the effects of the invention are exerted, but is preferably 4 to 100 parts by mass (as the equivalent of muirapuama drug substance) with respect to 1 part by mass of L-proline, and 10 to 50 Part by mass is more preferable.
[0019]
The present invention includes vitamins, xanthine derivatives, crude drugs, natural products, excipients, pH adjusting agents, cooling agents, suspending agents, antifoaming agents, viscosities, in a qualitative and quantitative range that does not impair the effects of the invention. Thickeners, solubilizers, disintegrants, binders, lubricants, antioxidants, coating agents, colorants, flavoring agents, surfactants, plasticizers, fragrances etc. Oral or parenteral preparations such as tablets, granules, powders, capsules, dry syrups, chewable tablets, and transmucosal agents can be used.
[0020]
【The invention's effect】
According to the present invention, it is possible to provide a highly safe oral composition that can prevent or ameliorate hyperlipidemia, and can further prevent or ameliorate obesity.
[0021]
【Example】
The present invention will be specifically described below with reference to examples and test examples. In addition, the crude drug component was described in the amount of crude drug equivalent.
Example 1
(Component) Blending amount L-proline 50g
Muirapuama 1000g (concentration in bulk drug)
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 the components of 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
(Component) Blending amount L-proline 30g
Muirapuama 1000g (concentration in bulk drug)
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
(Ingredients) Blending amount Muirapuama 2400g (concentration in bulk drug)
L-proline 60g
Cholestyramine 30g
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.
[0022]
Test Example LVG (SYR) BR male hamster (Syrian hamster, 3 weeks old) was used for the test. 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.
The hyperlipidemia-inducing group was further divided into four groups: a control group, an L-proline administration group, a muirapuama extract administration group, and a combination group of L-proline and muirapuama extract. In normal and control groups, L-proline was administered at a dose of 300 mg / kg, L-proline was administered at a dose of 300 mg / kg, and Mirapuama extract was administered at a dose of 500 mg / kg. In the combination group, L-proline was orally administered once daily for 14 days at a dose of 300 mg / kg and muirapuama extract at a dose of 500 mg / kg. The day after the final administration, blood was collected from the posterior vena cava under ether anesthesia, and the serum was immediately separated.
Triglyceride (abbreviated as TG) (FIG. 1), free fatty acid (abbreviated NEFA) (FIG. 2), and total cholesterol (abbreviated as T-Cho) (FIG. 3) in the obtained serum were measured with each measurement kit (triglyceride G). -Test Wako, NEFA C-Test Wako, Cholesterol C2-Test Wako).
[0023]
[Table 1]

(result)
[0024]
As shown in (FIG. 1), (FIG. 2), and (FIG. 3), when a hamster is ingested with a high-fat and high-cholesterol diet for 15 days, TG and NEFA in serum, T-Cho was significantly increased and hyperlipidemia was induced. The L-proline 300 mg / kg administration group and the muirapuama extract 500 mg / kg administration group did not affect serum TG, NEFA, and T-Cho, but the L-proline 300 mg / kg and muirapuama extract 500 mg / kg combination group Suppressed the increase of serum TG, NEFA, and T-cho.
When the safety was confirmed, no abnormal behavior was observed in the rats during the administration period, and the body weight increased steadily. No abnormal findings were found at the time of dissection.
From the above results, it has been clarified that the combined administration of L-proline and muirapuama extract has a preventive or ameliorating action against hyperlipidemia and has no problem with safety.
[Brief description of the drawings]
FIG. 1 shows the serum triglyceride concentration of rats used in the experiment.
FIG. 2 shows the serum free fatty acid concentration of rats used in the experiment.
FIG. 3 shows the total cholesterol concentration of rats used in the experiment.

Claims (2)

A composition for preventing or improving hyperlipidemia, comprising L-proline and muirapuama. The composition according to claim 1, which is an oral preparation.

Images