JP3549997B2 - Food composition and pharmaceutical composition having lipase inhibitory effect - Google Patents

Description

【００４０】
ローズマリー抽出物および延命草抽出物のリパーゼ阻害率を、図１に示す。点描された棒はローズマリー抽出物を、白棒は延命草抽出物を示す。横軸は濃度（重量％＝（Ｗ／Ｖ）％）を、縦軸はリパーゼ阻害率（％）を示す。ローズマリー抽出物は、０．０２５重量％および０．１重量％の時、それぞれ７２％および８６％のリパーゼ阻害率を示した。一方、延命草抽出物は、０．０２５重量％および０．１重量％の時、それぞれ５４％および７９％のリパーゼ阻害率を示した。
【００４１】
以上の結果より、ローズマリー抽出物および延命草抽出物が、高いリパーゼ阻害効果を有することが認められた。
【００４２】
従って、本発明において「リパーゼ阻害効果を有する植物または植物抽出物」とは、上記の条件（０．０２５重量％）で、少なくとも約３０％、好ましくは約５０％、より好ましくは約７０％以上の阻害率を示す植物抽出物、およびかかる抽出物を与える植物をいう。
【００４３】
実施例４ 食品Ａの調製
ローズマリー抽出物および延命草抽出物を有効成分として、以下の表１の組成を有する食品Ａを調製した。
【００４４】
【表１】

【００４５】
各成分を流動造粒装置中で混合した後、水を噴霧して造粒を行い、入風温度８０℃で乾燥し、食品Ａを得た。
【００４６】
実施例５ 食品Ｂの調製
延命草抽出物を有効成分として、以下の表２の組成を有する食品Ｂを調製した。
【００４７】
【表２】

【００４８】
上記の成分を水１０Ｋｇと十分に混合した後、６０℃に加温してペースト状とした。これを、予め７０℃に加温しておいた大豆油５０Ｋｇの中に投入し、イカリ型攪拌羽（２枚）を装着した攪拌機で十分に混合した。大豆油中にペーストが分散されたのを確認した後、混合物を５℃まで冷却した後、濾過を行い、生成した粒子を分離した。得られた粒子をｎ−ヘキサンで洗浄、乾燥した後、常法に従い、上記成分を含有するマイクロカプセル（食品Ｂ）を得た。
【００４９】
実施例６ 錠剤の調製
ローズマリー抽出物を有効成分として、以下の表３の成分を用いて錠剤を調製した。
【００５０】
【表３】

【００５１】
実施例７ 静脈内用製剤の調製
延命草抽出物を有効成分として、以下の表４の成分を用いて静脈内用製剤を調製した。
【００５２】
【表４】

【００５３】
実施例８ 食品組成物および医薬組成物の投与およびその結果
上記実施例３〜７で得られた食品または医薬組成物をラット、マウスなどの実験動物に与えたところ、いずれの食品および医薬組成物についても良好な結果が得られた。
【００５４】
【発明の効果】
本発明によれば、ローズマリー抽出物または延命草抽出物などを有効成分として含有する、肥満症を抑制または予防し得る安全性の高い食品組成物および医薬組成物が提供される。更に、シソ科植物またはその抽出物は、リパーゼに起因する食品の劣化、悪臭を防止するためにも利用することができる。
【図面の簡単な説明】
【図１】ローズマリー抽出物および延命草抽出物のリパーゼ阻害率を示すグラフである。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a highly safe food composition and a pharmaceutical composition having a lipase inhibitory effect. More particularly, it relates to a food composition and a pharmaceutical composition containing a Labiatae plant (especially rosemary (mannan wax) or life-extending grass) or a Labiatae plant extract, thereby having a lipase inhibitory effect. Since pancreatic lipase is involved in the digestion and absorption of lipids in vivo, inhibition of pancreatic lipase using the food composition or pharmaceutical composition of the present invention suppresses lipid accumulation in the body and suppresses obesity And can be prevented.
[0002]
[Prior art]
In recent years, the diet of Japanese people has been remarkably westernized and the calories have been increasing. In particular, an excessive intake of lipids causes obesity, which is also called modern civilization disease. Obesity is one of social problems because it is closely related to various diseases such as hyperlipidemia, arteriosclerosis, and diabetes, and it is desired to provide a method for improving obesity.
[0003]
Methods for improving obesity include diet and exercise therapy. However, diet and exercise regimens often result in transient weight loss. It is known that a temporary weight loss causes a rebound of the body weight and may trigger various adult diseases, which is not preferable. Next, there is a method using a central appetite suppressant. However, it is known that a central appetite suppressant has side effects, and there is a problem in safety. Therefore, it is still desirable to provide a method for improving obesity more safely.
[0004]
By the way, it is known that various plants contain various physiologically active ingredients. For example, Japanese Patent Publication No. 1-44230 discloses that herbal spices (particularly rosemary and sage) have an antioxidant effect. Japanese Patent Application Laid-Open No. 2-304409 describes that many components including an antibacterial substance are extracted by extracting a Labiatae plant (for example, rosemary and life-extending grass) with an aqueous alcohol solution. JP-A-4-13630 describes that extracts of rosemary and sage have an inhibitory effect on plaque formation of Streptococcus mutans, an oral microorganism involved in dental caries and plaque formation. I have. However, these prior arts do not describe that Labiatae plants (especially rosemary) and their extracts have a lipase inhibitory effect.
[0005]
In addition, life-prolonging herbs have been used in folk medicine since ancient times as a bitter stomach medicine. Japanese Patent Application Laid-Open No. 1-172333 discloses that a life-prolonging grass (herb medicine which is a dried product of Hioki-koi or Kurobana-hioki-koi) or an extract thereof has a specific bacteriostatic and bactericidal action against streptococcus Streptococcus in vitro or in vivo. Is described. JP-A-59-5176 describes that some diterpenoid compounds contained in a dried above-ground extract of San Inoki sorghum have antitumor activity. JP-A-48-5911 describes a method for extracting a medically active ingredient from lentils of a Labiatae plant. As for the medical effect of the effective substance obtained by this method, a gastric secretion inhibitory effect is described. JP-A-5-310537 describes that an extract of Hioki koshi has an effect of preventing hair loss, hair growth and hair growth. However, these prior arts do not describe that Labiatae plants (especially life-prolonging plants) and their extracts have a lipase inhibitory effect.
[0006]
As described above, it has not been known that a Labiatae plant or an extract thereof has a lipase inhibitory effect.
[0007]
[Problems to be solved by the invention]
The present invention has been made to solve the above problems, and in particular, has an extremely high inhibitory effect on pancreatic lipase, which is a key to obesity, in order to regulate digestion and absorption of lipids in a living body. An object of the present invention is to provide a highly safe food composition and a pharmaceutical composition which can suppress the accumulation of lipids in the body by a lipase inhibitory action and thereby contribute to the suppression and prevention of obesity.
[0008]
[Means for Solving the Problems]
In order to solve the above problems, the present inventors inhibit and prevent obesity in humans by inhibiting pancreatic lipase, which is the first enzyme of digestion and absorption of lipids, and suppressing accumulation of lipids in the body. The components were searched diligently. As a result, it has been found that Labiatae plants (especially rosemary and life-extending grasses) and their extracts have excellent lipase inhibitory effects.
[0009]
That is, the present invention provides a lipase inhibitor comprising a rosemary extract. The rosemary extract is preferably extracted with water and / or a polar organic solvent.
[0010]
The present invention also provides a food containing the lipase inhibitor and a food material, and a pharmaceutical composition containing the lipase inhibitor and a pharmaceutically acceptable carrier.
[0015]
BEST MODE FOR CARRYING OUT THE INVENTION
As used herein, the term "Labiatae plant" refers to a plant belonging to the Labiatae family. Lamiaceae plants include the genus Rosmarius and the genus Yamatta (Genus Isodon). Rosemary (Rosmarius officinalis) is mentioned as an example of a plant belonging to the genus Mannerou. In this specification, “extended lifegrass” refers to a group of plants commonly referred to as lifelong grass among the genus Yamanaka. Examples of the life-extending grass include Hioki-koshi (Isdon japonica), Kurobana-kioki (Isodon trichocarpus), and Takakuma-kioki (Isdon shikokinus var. Intermodius).
[0016]
As a Labiatae plant, any part of a plant body may be used. When the Labiatae plant is rosemary, the aerial part is preferred, and the foliage is even more preferred. When the Labiatae is a life-extending plant, the whole plant is preferable, and the foliage is more preferable. The Labiatae plant may be used as it is after being collected, or may be used after being subjected to drying treatment such as sun drying and shade drying. When the Lamiaceae plant is life-extending grass, a commercially available crude drug “Enmei-so”, which is a dried product of life-extending grass, can also be used.
[0017]
The Labiatae plant extract is obtained by solvent-extracting the Labiatae plant. The Labiatae plant to be subjected to the extraction may be in any form, but is preferably a cut or crushed strip or powder in terms of extraction efficiency. The method and means of solvent extraction are not limited. The Labiatae plant extract may be the extract itself obtained by solvent extraction, or a concentrated solution, diluted or diluted by concentrating or diluting the extract, or distilling off the solvent in the extract. It may be a liquid, a dried product or a granule.
[0018]
The solvent used for the extraction of the Labiatae extract is water, an organic solvent, or a mixture of water and an organic solvent. Examples of the organic solvent used for the extraction include methanol, ethanol, n-propanol, acetone, ethyl acetate, ether, methylene chloride, chloroform, benzene, carbon tetrachloride, petroleum ether, and the like. preferable.
[0019]
The extraction temperature is not particularly limited, and may be room temperature, but is preferably heated to reflux. The extraction time varies depending on the extraction temperature, but is usually 2 to 48 hours. After extraction, a crude extract is obtained by filtration or centrifugation, and then, if desired, post-treatment such as concentration, dilution or drying is performed to obtain an extract.
[0020]
(Food composition)
The food composition of the present invention contains at least one of a Labiatae plant and a Labiatae plant extract, preferably a plant belonging to the genus Mannerou or the genus Yamanaka, or an extract thereof, more preferably rose Contains marie or prolonged life grass or extracts thereof. The Labiatae plant or Labiatae plant extract may include a single species or a plurality of species.
[0021]
In the food composition of the present invention, in the case of Labiatae plants, on a dry weight basis, in the case of Labiatae plant extracts, on a solids basis, typically from about 0.001% to about 99% by weight, preferably About 0.01% to about 50% by weight, more preferably about 0.05% to about 20% by weight.
[0022]
The food composition of the present invention further comprises food ingredients commonly used in the art. Examples of food raw materials include lactose, dextrose, sucrose, sorbitol, mannitol, apple fiber, soy fiber, meat extract, black vinegar extract, gelatin, corn starch, honey, animal and vegetable fats and oils, and polysaccharides. The food composition of the present invention may include one or more of these food ingredients.
[0023]
The food composition of the present invention may further contain one or more components such as a lubricant, an emulsifier, a suspending agent, an antioxidant, a preservative, a sweetener and a flavoring agent, in addition to the above-mentioned food ingredients. Further, it may further contain other active ingredients including water-soluble vitamins and oil-soluble vitamins. Those skilled in the art can easily select appropriate components that do not interfere with the lipase inhibitory effect of the Labiatae plant or Labiatae extract.
[0024]
The food composition of the present invention is manufactured by a method well known in the art. The form of the food composition of the present invention is not particularly limited. Examples of the form of the food composition of the present invention include granules, tablet confectionery, jelly, candy, and beverages.
[0025]
The food composition of the present invention is ingested as needed.
[0026]
(Pharmaceutical composition)
The pharmaceutical composition of the present invention contains at least one of a Labiatae plant and a Labiatae plant extract, and preferably contains a plant belonging to the genus Mannerou or the genus Yamanaka, or an extract thereof, and more preferably contains rose. Contains marie or prolonged life grass or extracts thereof. The Labiatae plant or Labiatae plant extract may include a single species or a plurality of species.
[0027]
In the pharmaceutical composition of the present invention, in the case of Labiatae plants, by dry weight, in the case of Labiatae extracts, by solid content weight, typically about 0.001% to about 99% by weight, preferably About 0.01% to about 50% by weight, more preferably about 0.01% to about 20% by weight.
[0028]
The pharmaceutical composition of the present invention further includes a pharmaceutically acceptable carrier. Examples of carriers include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose derivatives, tragacanth, gelatin, syrup, methyl hydroxybenzoate. , Talc, magnesium stearate, water, mineral oil and the like. The pharmaceutical composition of the present invention may contain one or more of these carriers.
[0029]
The pharmaceutical composition of the present invention comprises a lubricant, an emulsifier, a suspending agent, an antioxidant, an antiseptic, a sweetener and a flavoring agent, and the like, and water-soluble vitamins and oils as in the case of the food composition described above. It may contain one or more other active ingredients including soluble vitamins and the like.
[0030]
The pharmaceutical composition of the present invention is manufactured by a method well known in the art.
[0031]
The form of the pharmaceutical composition of the present invention is not particularly limited. Examples of the form of the pharmaceutical composition of the present invention include external preparations such as ointments and patches; internal preparations such as tablets, pills, powders, syrups, emulsions, liquids, suspensions, Examples include forms such as gelatin capsules; and forms such as injections and sprays. Pharmaceutical compositions in the form of injections, sprays and the like can be administered by transdermal, injection, intranasal routes and the like.
[0032]
The Labiatae plant or Labiatae extract used in the pharmaceutical composition of the present invention is effective over a wide dosage range. Therefore, the daily dose of a Labiatae plant or Labiatae plant extract is typically about 0.01 mg to about 1000 mg per 1 kg of body weight in terms of the solid content of the Labiatae plant extract, Preferably, the range is from about 0.1 mg to about 500 mg, more preferably, from about 1 mg to about 200 mg. This dose is administered once or in several divided doses. The actual dose will be determined taking into consideration the age, weight and severity of the condition to be treated and the route of administration chosen.
[0033]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples.
[0034]
Example 1 Production of Rosemary Extract To 320 kg of dried and chopped rosemary foliage, 10 times the amount of ordinary water (tap water) was added and digested at 95 ° C. or higher for 1 hour. After allowing to cool to 65 ° C., the mixture was centrifuged to obtain an extract. To the residue was added 8 volumes of ordinary water again, followed by digestion and centrifugation in the same manner to obtain an extract. This extract was combined with the previous extract and concentrated under reduced pressure at 40 ° C. to obtain 130 liter of concentrated extract. This extract was spray-dried to obtain 35 kg of rosemary extract.
[0035]
Example 2 Manufacture of Extended Life Grass Extract 320 ml of Enmeisou grass (whole plant, coarsely cut; manufactured by Takasago Pharmaceutical Co., Ltd.) sold as crude drug was added with 10 times the amount of ordinary water, and digested at 95 ° C. or more for 1 hour. did. After allowing to cool to 65 ° C., the mixture was centrifuged to obtain an extract. To the residue was added 8 volumes of ordinary water again, followed by digestion and centrifugation in the same manner to obtain an extract. This extract was combined with the previous extract and concentrated under reduced pressure at 40 ° C. to obtain 130 liter of concentrated extract. This extract was spray-dried to obtain 38 kg of life-extended grass extract.
[0036]
Example 3 Measurement of lipase inhibition rate of rosemary extract and life-extended grass extract The lipase inhibition rate of rosemary extract and life-extended grass extract obtained in Examples 1 and 2 was measured. The lipase inhibition rate was measured using lipase (manufactured by Sigma, from pig pancreas, 50 μg / ml) and “Lipase Kit S” manufactured by Dainippon Pharmaceutical. The measuring method followed the manufacturer's instructions.
[0037]
The measurement method is briefly described as follows. 300 μl of a sample aqueous solution containing 0.025% by weight or 0.01% by weight of the rosemary extract or the life-extending grass extract (control: 300 μl of water), 80 μl of 0.05 mg / ml lipase, and a coloring solution (0.1 mg 1 ml of a buffer containing 5,5-'dithiobis (2-nitrobenzoic acid) / ml, and then add 20 μl of an esterase inhibitor (3.48 mg / ml of phenylmethylsulfonyl fluoride). After heating these reaction solutions at 30 ° C. for 5 minutes, 100 μl of a substrate solution (6.69 mg / ml methylcapnyl tributyrate + 5.73 mg / ml sodium dodecyl sulfate) was added, and the mixture was darkened at 30 ° C. for 30 minutes. React under the conditions. Thereafter, 2 ml of a reaction stop solution is added to stop the enzyme reaction. A blind sample was prepared by adding a sample aqueous solution, a lipase, a coloring solution, and an esterase inhibitor, heating the mixture at 30 ° C. for 5 minutes, and then at 30 ° C. for 30 minutes. Is added. The absorbance at 412 nm of each sample is measured with an absorbance meter. The lipase activity value is calculated from the absorbance difference between the absorbance of the test sample and the corresponding absorbance of the blind sample (absorbance difference 0.001 = 0.147 IU / liter).
[0038]
Using the obtained lipase activity value, the lipase inhibition rate was calculated by the following equation.
[0039]
(Equation 1)

[0040]
FIG. 1 shows the lipase inhibition rates of the rosemary extract and the life-extending grass extract. The stippled bars indicate the rosemary extract, and the white bars indicate the life-extending grass extract. The horizontal axis represents the concentration (% by weight = (W / V)%), and the vertical axis represents the lipase inhibition rate (%). Rosemary extract showed 72% and 86% lipase inhibition at 0.025% and 0.1% by weight, respectively. On the other hand, the life-extending grass extract showed lipase inhibition rates of 54% and 79% at 0.025% by weight and 0.1% by weight, respectively.
[0041]
From the above results, it was confirmed that the rosemary extract and the life-extending grass extract had high lipase inhibitory effects.
[0042]
Therefore, in the present invention, “a plant or a plant extract having a lipase inhibitory effect” means at least about 30%, preferably about 50%, more preferably about 70% or more under the above-mentioned conditions (0.025% by weight). Plant extract showing the inhibitory rate of, and a plant giving such an extract.
[0043]
Example 4 Preparation of Food A Food A having the composition shown in Table 1 below was prepared using the rosemary extract and the life-extending grass extract as active ingredients.
[0044]
[Table 1]

[0045]
After mixing each component in a fluidized-granulation device, water was sprayed to perform granulation, and dried at an air inlet temperature of 80 ° C. to obtain Food A.
[0046]
Example 5 Preparation of Food B Food B having the composition shown in Table 2 below was prepared using the life-extending grass extract as an active ingredient.
[0047]
[Table 2]

[0048]
After sufficiently mixing the above components with 10 kg of water, the mixture was heated to 60 ° C. to form a paste. This was put into 50 kg of soybean oil which had been heated to 70 ° C. in advance, and was sufficiently mixed with a stirrer equipped with squid-type stirring blades (two pieces). After confirming that the paste was dispersed in the soybean oil, the mixture was cooled to 5 ° C., and then filtered to separate generated particles. After the obtained particles were washed with n-hexane and dried, microcapsules (food B) containing the above components were obtained according to a conventional method.
[0049]
Example 6 Preparation of Tablet A tablet was prepared using the rosemary extract as an active ingredient and the components shown in Table 3 below.
[0050]
[Table 3]

[0051]
Example 7 Preparation of Intravenous Formulation An intravenous formulation was prepared using the life-extending grass extract as an active ingredient and the components shown in Table 4 below.
[0052]
[Table 4]

[0053]
Example 8 Administration of Food Composition and Pharmaceutical Composition and Resulting The food or pharmaceutical composition obtained in Examples 3 to 7 above was given to experimental animals such as rats and mice. Good results were also obtained for
[0054]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, the highly safe food composition and pharmaceutical composition which can suppress or prevent obesity are provided which contain a rosemary extract, a life-extending grass extract, etc. as an active ingredient. Furthermore, the Labiatae plant or its extract can also be used to prevent food deterioration and odor caused by lipase.
[Brief description of the drawings]
FIG. 1 is a graph showing the lipase inhibition rates of a rosemary extract and a life-extending grass extract.

Claims (4)

Lipase inhibitor consisting of rosemary extract. The lipase inhibitor according to claim 1, wherein the rosemary extract is extracted with water and / or a polar organic solvent. A food comprising the lipase inhibitor according to claim 1 and a food raw material. A pharmaceutical composition comprising the lipase inhibitor according to claim 1 and a pharmaceutically acceptable carrier.

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