JP2004256476A - Composition for preventing or improving hyperlipidemia - Google Patents
Composition for preventing or improving hyperlipidemia Download PDFInfo
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- JP2004256476A JP2004256476A JP2003050700A JP2003050700A JP2004256476A JP 2004256476 A JP2004256476 A JP 2004256476A JP 2003050700 A JP2003050700 A JP 2003050700A JP 2003050700 A JP2003050700 A JP 2003050700A JP 2004256476 A JP2004256476 A JP 2004256476A
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Abstract
Description
【０００１】
【発明の属する技術分野】
本発明は、副作用がなく安全な高脂血症の予防または改善用組成物、およびこれを含有する医薬品、医薬部外品または食品に関する。
【０００２】
【従来の技術】
現在、運動不足や食べ過ぎ等の生活習慣が原因で肥満になってしまう人が増えている。この肥満は、高脂血症と密接に関連している。また、高脂血症は、高血圧や糖尿病とも相関している。そして、高脂血症、糖尿病および高血圧は、心臓病や動脈硬化等の重大な病気を引き起こす原因と考えられている。
【０００３】
高脂血症は、血液中の脂質濃度が上昇する状態になる疾患である。近年の食文化の欧米化に伴い、脂肪の摂取が上昇しているため、高脂血症の患者の数も上昇している。高脂血症は動脈硬化の危険因子のひとつである。
【０００４】
この高脂血症を治療するのに、運動療法や食事制限の方法に加え、医薬品の投与等の方法がある。食事制限については従来の食事の内容、量を制限され、患者の受けるストレスは非常に大きく負担がかかる。また、食欲抑制剤や脂質代用品の使用も考えられるが、安全性や効果について不安がある。さらに、運動療法も現代社会を考慮すると継続することに問題がある。
【０００５】
このような状況の中、副作用なく安全な高脂血症を予防又は改善する医薬品、医薬部外品若しくは食品の開発が期待されていた。
【０００６】
そこで、発明者らはアミノ酸の１種であるＬ−プロリンとムイラプアマとの組成物を服用すると、血中のコレステロール濃度、トリグリセライド濃度及び遊離脂肪酸濃度の上昇を抑制することを見出した。高脂血症は、これらの血中脂質濃度を指標に診断され、血中脂質の濃度を効果的に抑制することは非常に有用である。
【０００７】
本発明に先立ち、Ｌ−プロリンが血中トリグリセライド濃度の上昇を抑制することも見出されている（特許文献１）。しかし、この技術はＬ−プロリンを１０００ｍｇ／ｋｇ投与することが必要であり、本願発明の３００ｍｇ／ｋｇと比較して多く投与しなければならない。
【特許文献１】
特願２００２−１９８３２２
【０００８】
【発明が解決しようとする課題】
本発明の目的は、副作用がなく、安全かつ効果的な高脂血症の予防または治療に有用な組成物を提供することである。
【０００９】
【課題を解決するための手段】
本発明者らは、上記課題を解決する目的で鋭意検討を行った結果、Ｌ−プロリン単独では効果がみられない濃度である低濃度（３００ｍｇ／ｋｇ）においても、ムイラプアマを併用することにより、血清トリグリセライド濃度だけでなく、血清コレステロール濃度及び遊離脂肪酸濃度の上昇も抑制することを見いだした。
【００１０】
すなわち、Ｌ−プロリンとムイラプアマを併用することにより高脂血症の予防あるいは改善にも有効であることを見いだし本発明を完成した。
【００１１】
【発明の実施の形態】
本発明は高脂血症の予防または改善に有効である。さらに、高脂血症を改善することにより肥満を予防あるいは改善することが可能である。
【００１２】
本発明で用いるＬ−プロリンは体を構成するアミノ酸の一つであり、皮膚の主要構成成分であるヒドロキシプロリンの原料として、体内で利用されることが知られている。プロリンは大麦、小麦、はとむぎなどの穀類、大豆加工食品、魚類、肉類に多く含まれ、長期間摂取しても安全性が高い。
【００１３】
また、Ｌ−プロリンの有効投与量は、年齢、性別などを考慮して適宜増減できるが、通常、成人で１日１０ｍｇ〜５０００ｍｇであり、好ましくは１００ｍｇ〜３０００ｍｇである。
【００１４】
本発明に用いるムイラプアマの基原植物は、ブラジル・アマゾン川流域に生育するボロボロノキ科（Ｏｌａｃａｃｅａｅ）に属し、Ｐｔｙｃｈｏｐｅｔａｌｕｍ ｏｌａｃｏｉｄｅｓの他、Ｐｔｙｃｈｏｐｅｔａｌｕｍ ｕｎｃｉｎａｔｕｍ、Ｌｉｒｉｏｓｍａ ｏｖａｔａなどがあげられ、好ましいものはＰｔｙｃｈｏｐｅｔａｌｕｍ ｏｌａｃｏｉｄｅｓである。本発明ではこれらの基原植物の根が用いられる。
【００１５】
本発明で用いるムイラプアマは生薬末の他、エキスも使用することができる。ここでエキスとは、生薬抽出物、濃縮エキス、乾燥エキスなどいずれの形態も含む。エキスは抽出溶媒として水、アルコール（メタノール、エタノール、プロパノール、イソプロパノールなど）、酢酸エチル、アセトン、それらの混液などを用いて通常の方法で製造することができる。
【００１６】
本発明で用いるムイラプアマは、民間療法で古くから使用されている生薬であるので、その安全性は確保されている。そのため、長期間にわたる連続投与も可能である。
【００１７】
本発明におけるムイラプアマの有効投与量は、年齢、性別などを考慮して適宜増減できるが、通常、原生薬換算量として成人で１日１０ｍｇ〜５０００ｍｇであり、好ましくは１００ｍｇ〜３０００ｍｇである。
【００１８】
Ｌ−プロリンとムイラプアマの組み合わせの配合比について、発明の効果を奏する限り特に限定されないが、Ｌ−プロリン１質量部に対し４〜１００質量部（ムイラプアマ原生薬換算量として）が好ましく、１０〜５０質量部がさらに好ましい。
【００１９】
本発明は、発明の効果を損なわない質的および量的範囲で、ビタミン、キサンチン誘導体、生薬、天然物、賦形剤、ｐＨ調製剤、清涼化剤、懸濁化剤、消泡剤、粘稠剤、溶解補助剤、崩壊剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味矯臭剤、界面活性剤、可塑剤、香料などを混合して常法により、液剤、錠剤、顆粒剤、散剤、カプセル剤、ドライシロップ剤、チュアブル錠、経粘膜剤などの経口または非経口製剤とすることができる。
【００２０】
【発明の効果】
本発明により、高脂血症を予防あるいは改善でき、さらには、肥満を予防あるいは改善することができる安全性の高い経口用組成物の提供が可能になった。
【００２１】
【実施例】
以下に実施例および試験例をあげ、本発明を具体的に説明する。なお、生薬成分は原生薬換算量で記載した。
実施例１
実施例２
実施例１の成分にさらにアスパルテーム１０ｇを加えて、同様にして造粒物を得た。この造粒物にステアリン酸マグネシウム、硬化ヒマシ油を適宜加えて均一に混合し、分包剤１００包を調製した。
実施例３
実施例４
【００２２】
試験例
試験にはＬＶＧ（ＳＹＲ）ＢＲ系雄性ハムスター（シリアンハムスター、３週齢）を用いた。実験に使用するまで約１週間の予備飼育を行った後、正常食摂取群（正常群）および高脂肪・高コレステロール食摂取群（高脂血症惹起群）の２群に分けた。正常群および高脂血症惹起群にはそれぞれ表１に示す成分組成の正常食あるいは高脂肪・高コレステロール食を１５日間与えた。
高脂血症惹起群はさらに対照群、Ｌ−プロリン投与群、ムイラプアマエキス投与群、Ｌ−プロリンとムイラプアマエキスの併用群の４群に分けた。正常群および対照群には水をＬ−プロリン投与群にはＬ−プロリンを３００ｍｇ／ｋｇの用量で、ムイラプアマエキス投与群にはムイラプアマエキスを５００ｍｇ／ｋｇの用量で、Ｌ−プロリンとムイラプアマエキスの併用群には、Ｌ−プロリンを３００ｍｇ／ｋｇ、ムイラプアマエキスを５００ｍｇ／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。
得られた血清中のトリグリセライド（ＴＧと略記）（図１）および遊離脂肪酸（ＮＥＦＡと略記）（図２）、総コレステロール（Ｔ−Ｃｈｏと略記）（図３）濃度は各測定キット（トリグリセライドＧ−テストワコー、ＮＥＦＡ Ｃ−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。
【００２３】
【表１】
【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]
TECHNICAL FIELD 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 composition.
[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 linked to hyperlipidemia. Hyperlipidemia is also correlated with hypertension and diabetes. And, hyperlipidemia, diabetes and hypertension are considered to cause serious diseases such as heart disease and arteriosclerosis.
[0003]
Hyperlipidemia is a disease in which the concentration of lipids in the blood rises. With the westernization of food culture in recent years, the intake of fats has been increasing, and 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 exercise therapy and dietary restriction. With regard to dietary restrictions, the content and amount of conventional diets are limited, and the stress on the patient is extremely large. The use of an appetite suppressant or a lipid substitute may also be considered, but there are concerns about safety and effects. Furthermore, there is a problem in that exercise therapy is continued in consideration of modern society.
[0005]
Under such circumstances, development of drugs, quasi-drugs, or foods that can safely prevent or improve hyperlipidemia without side effects has been expected.
[0006]
Thus, the present inventors have found that taking a composition of L-proline, one of the amino acids, and muirapuama suppresses increases in blood cholesterol, triglyceride, and free fatty acid concentrations. Hyperlipidemia is diagnosed using these blood lipid levels as indicators, and it is very useful to effectively suppress blood lipid levels.
[0007]
Prior to the present invention, it has also been found that L-proline suppresses an increase in blood triglyceride concentration (Patent Document 1). However, this technique requires that L-proline be administered at 1000 mg / kg, which must be administered more than the 300 mg / kg of the present invention.
[Patent Document 1]
Japanese Patent Application No. 2002-198322
[0008]
[Problems to be solved by the invention]
An object of the present invention is to provide a composition useful for safe and effective prevention or treatment of hyperlipidemia without side effects.
[0009]
[Means for Solving the Problems]
The present inventors have conducted intensive studies for the purpose of solving the above problems, and as a result, even at a low concentration (300 mg / kg) at which L-proline alone is not effective, by using muirapuama in combination, It has been found that not only increases in serum triglyceride concentration but also in serum cholesterol concentration and free fatty acid concentration are suppressed.
[0010]
That is, they found that the combined use of L-proline and muirapuama was also effective in preventing or ameliorating hyperlipidemia, and completed the present invention.
[0011]
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is effective for preventing or improving hyperlipidemia. Furthermore, obesity can be prevented or ameliorated by improving hyperlipidemia.
[0012]
L-proline used in the present invention 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 main constituent of skin. Proline is contained abundantly in grains such as barley, wheat, and barley, processed soy foods, fish, and meat, and is highly safe even when taken for a long time.
[0013]
The effective dose of L-proline can be appropriately increased or decreased in consideration of age, sex, and the like, but is usually 10 mg to 5000 mg, preferably 100 mg to 3000 mg per day for an adult.
[0014]
The root plant of muirapuama used in the present invention belongs to the family Olacaceae, which grows in the Amazon river basin in Brazil, and includes Ptychopetalum olacoides, Ptychopetalum uncinatum, Liriosoma ovata, and the like. In the present invention, the roots of these base plants are used.
[0015]
The muirapuama used in the present invention may be an extract in addition to a crude drug powder. Here, the extract includes any form such as a crude drug extract, a concentrated extract, and a dried extract. The extract can be produced by an ordinary method using water, an alcohol (such as methanol, ethanol, propanol, or isopropanol), ethyl acetate, acetone, or a mixture thereof as an extraction solvent.
[0016]
Muirapuama used in the present invention is a crude drug that has been used for a long time in folk remedies, so its safety is ensured. Therefore, continuous administration over a long period of time is also possible.
[0017]
The effective dose of muirapuama in the present invention can be appropriately increased or decreased in consideration of age, gender, etc., and is usually 10 mg to 5000 mg, preferably 100 mg to 3000 mg per day as an equivalent of a crude drug in an adult.
[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 exhibited, but is preferably 4 to 100 parts by mass (as a muirapuama crude drug equivalent) per 1 part by mass of L-proline, and 10 to 50 parts by mass. Parts by mass are more preferred.
[0019]
The present invention provides vitamins, xanthine derivatives, crude drugs, natural products, excipients, pH adjusters, fresheners, suspending agents, defoamers, viscous agents within a qualitative and quantitative range that does not impair the effects of the present invention. Thickeners, dissolution aids, disintegrants, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, surfactants, plasticizers, fragrances, etc. Oral or parenteral preparations such as tablets, granules, powders, capsules, dry syrups, chewable tablets and transmucosal preparations can be made.
[0020]
【The invention's effect】
According to the present invention, it has become possible to provide a highly safe oral composition capable of preventing or improving hyperlipidemia and preventing or improving obesity.
[0021]
【Example】
Hereinafter, the present invention will be described specifically with reference to Examples and Test Examples. In addition, crude drug components are described in terms of the amount of the crude drug.
Example 1
Example 2
10 g of aspartame was further added to the components of Example 1, and a granulated product was obtained in the same manner. Magnesium stearate and hydrogenated castor oil were appropriately added to the granules and uniformly mixed to prepare 100 sachets.
Example 3
Example 4
[0022]
Test Example In the test, an LVG (SYR) BR male hamster (Syrian hamster, 3 weeks old) was used. After pre-breeding for about one week before use in the experiment, the animals were divided into two groups: a normal diet intake group (normal group) and a high fat / high cholesterol diet intake group (hyperlipidemia-inducing group). Each of the normal group and the hyperlipidemic group was fed 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. Water and L-proline were administered to the normal and control groups at a dose of 300 mg / kg for the L-proline group, and muirapuama extract at a dose of 500 mg / kg for the muirapuama extract group. 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. On the day after the final administration, blood was collected from the posterior vena cava under ether anesthesia, and the serum was immediately separated.
The concentration of triglyceride (abbreviated as TG) (FIG. 1), free fatty acid (abbreviated as NEFA) (FIG. 2), and total cholesterol (abbreviated as T-Cho) (FIG. 3) in the obtained serum were measured using the respective measurement kits (triglyceride G). -Test Wako, NEFA C-Test Wako, Cholesterol C2-Test Wako).
[0023]
[Table 1]
[0024]
As shown in (FIG. 1), (FIG. 2) and (FIG. 3), when hamsters were fed a high fat / high cholesterol diet for 15 days every day, TG and NEFA in serum, T-Cho was significantly increased and hyperlipidemia was induced. The L-
As a result of confirming the safety, no abnormal behavior was observed in the rats during the administration period, and the weight increased steadily. No abnormal findings were found at the time of dissection.
From the above results, it was clarified that combined administration of L-proline and muirapuama extract has a preventive or ameliorating effect on hyperlipidemia, and there is no problem in safety.
[Brief description of the drawings]
FIG. 1 shows the concentration of triglyceride in serum of rats used in the experiment.
FIG. 2 shows the concentration of free fatty acids in the serum of rats used in the experiment.
FIG. 3 shows the total cholesterol concentration of rats used in the experiment.
Claims (3)
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8372447B2 (en) * | 2010-08-03 | 2013-02-12 | Northern Innovations And Formulations Corp. | Compositions and methods for promoting weight loss and increasing energy |
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| US8372447B2 (en) * | 2010-08-03 | 2013-02-12 | Northern Innovations And Formulations Corp. | Compositions and methods for promoting weight loss and increasing energy |
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