JPH0977677A - Phosphatidyl choline sterol acyl transferase activity accelerator and composition containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an activity accelerator suitable for curing and prevention of hyperlipemia disease. SOLUTION: This accelerator is composed of essence of a plant body belonging to genus Paeonia in family Paeoniaceae (preferably Paeonia suffruticosa). Preferably, a using position of the plant body is a velamen part. The essence is preferably, e.g. an extract from a polar solvent or its distilled out substance from the solvent. Further, an optimum essence is preferably obtained by extracting the velamen part of the plant of genus Paeonia in family Paeoniaceae with hot water, adsorbing the extract on a suitable carrier, eluting with ethanol or a mixed solution of ethanol with water and condensing under a reduced pressure. A suitable administration dose of the essence obtained by such a process is 5-500mg for an adult per 1 day in dividing to several times in a case of oral administration or 1-100mg in a case of an injection. Otherwise, an administration as a food or a medicinal composition is also possible.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a phosphatidylcholinesterol acyltransferase activity promoter suitable for treating and preventing hyperlipidemia, and a composition containing the same.

[0002]

2. Description of the Related Art Phosphatidylcholinesterol acyltransferase, typified by lecithin cholesterol acyltransferase, reacts cholesterol in blood with lecithin to produce cholesterol ester and lysolecithin, which is then converted into cholesterol ester in blood. It is an enzyme that has the role of removing more. Therefore, when the function of this enzyme is not sufficient or cholesterol is present in the blood more than the activity of this enzyme, the amount of blood cholesterol increases and causes hyperlipidemia.

At present, several kinds of drugs such as mevallotin have already been used as hyperlipidemic agents, but none have a phosphatidylcholinesterol acyltransferase activity as a pharmacological mechanism, and therefore, phosphatidyl. There is no known effective therapeutic or preventive means for hyperlipidemia caused by reduced cholinesterol acyltransferase activity. Further, as a substance having a phosphatidylcholinesterol acyltransferase activity, a tricyclic compound, which is a central agonist, is known. However, since these compounds have a strong central agonist action, phosphatidylcholinesterol acyltransferase When used as a transferase activity promoter, it is used as a phosphatidylcholinesterol acyltransferase activity promoter in practice, since its central drug action, such as antidepressant action, has side effects. I couldn't do that. That is, the appearance of a new material having a phosphatidylcholinesterol acyltransferase activity promoting action has been awaited.

[0004] On the other hand, although it has been known that the essence of the plant belonging to the genus Buttonae, which belongs to the genus Buttonae, has an action of adjusting lipid balance, it is completely known that it has an action of promoting phosphatidylcholinesterol acyltransferase activity. There wasn't.

[0005]

The present invention has been made in view of such circumstances, and an object of the present invention is to provide a new phosphatidylcholinesterol acyltransferase activity promoter.

[0006]

[Means for Solving the Problems] In view of the above circumstances, a new phosphatidylcholinesterol acyltransferase activity promoting agent is sought, and various materials are used as targets for the phosphatidylcholinesterol acyltransferase activity promoting action, As a result of repeated diligent screening research, we found that the essence of the plant belonging to the genus Buttonae, a genus Button, has such a function, and completed the invention. Hereinafter, the invention will be described in detail.

(1) Phosphatidylcholinesterol acyltransferase activity accelerating agent of the present invention The phosphatidylcholinesterol acyltransferase activity accelerating agent of the present invention is composed of an essence of a plant belonging to the genus Button, genus Buttonae. Examples of plants belonging to the genus Buttonae include buttons and the like. The root bark is commercially available at Chinese herbal medicine stores and the like and is easily available. Here, the essence is the whole or a part of the plant itself, the whole or a part of the plant is dried, crushed, a processed product that is shredded, the whole or a part of the plant or a solvent-extracted product thereof, It is a generic term for those obtained by collecting only volatile components by steam distillation or the like, and those obtained by fractionating and purifying them by column chromatography or liquid-liquid extraction using silica gel, ODS, ion exchange resin or the like as a carrier. As for the extraction method, for example, a polar solvent may be added to a plant or a processed product thereof in an amount of 1 to 10 times, and soaked at room temperature for several days, and at a temperature near the boiling point for several hours. If necessary, insoluble matter may be removed by filtration or the solvent may be removed by concentration under reduced pressure. The solvent is not particularly limited, but water, ethanol or methanol, 1,3-
Alcohols such as butanediol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether and tetrahydrofuran, halogenated hydrocarbons such as methylene chloride and chloroform, esters such as ethyl acetate and methyl formate, nitriles such as acetonitrile. Suitable examples are the classes. Only one kind of these solvents may be used, or two or more kinds thereof may be mixed and used. The most preferable of these essences is one in which the root bark is extracted with warm water, adsorbed on Diaion HP-20 (manufactured by Mitsubishi Kasei) and eluted with ethanol or an ethanol-water mixture, and concentrated under reduced pressure. preferable. The essence thus obtained has excellent phosphatidylcholine sterol acyltransferase activity-promoting activity, and since it has a history of being used as a herbal medicine for many years as a source plant, it is also excellent in safety and therefore phosphatidylcholine. Sterol acyltransferase activity (LCAT)
It is very useful for the treatment and prevention of hyperlipidemia caused by the lack of In the case of oral administration, it is appropriate to administer 5 to 500 mg per adult daily in several divided doses. When used as an injection, 1-100
mg is suitable. Other administration routes may be similar to these.

(2) Composition of the present invention The composition of the present invention is characterized by containing one or more kinds selected from the essences of the plants belonging to the genus Button plant of the family Botanaceae. LC by blending these essences
The disorder of cholesterol homeostasis resulting from the lack of AT can be returned to normal. That is, when the amount of cholesterol in the blood is high and administered to a person with hyperlipidemia as a food or a pharmaceutical composition, the amount of cholesterol in the blood is lowered, and when administered to a person with arteriosclerosis as a food or a pharmaceutical composition, If it is improved and administered to a person with arterial atheroma as a food or a pharmaceutical composition, this is also improved. Furthermore, if the same administration is applied to a person who has not yet developed the disease, the onset of the disease can be prevented.

[0009] The pharmaceutical composition of the present invention is a phosphatidylcholinesterol acyltransferase activity-promoting agent of the present invention. Contains optional components of. As an optional component, an excipient, a bulking agent, a binder, a coating agent, a sugar coating agent, a stabilizer, a disintegrating agent, a coloring agent, a lubricant, a pH adjusting agent, a solubilizing agent, a dispersing agent, a thickening agent,
Examples include isotonic agents and the like. The pharmaceutical composition of the present invention can be obtained by formulating these optional components and the essence of the plant belonging to the genus Botanaceae in the usual manner. Further, if necessary, the pharmaceutical composition of the present invention can be mixed with a hyperlipidemic agent such as mevallotin and a cardiovascular drug such as chloropromazine.

The food composition of the present invention is characterized by containing a phosphatidylcholinesterol acyltransferase activity accelerating agent, an essence of a plant belonging to the genus Botanaceae, and an optional ingredient usually used in foods. . The type of food is not particularly limited, and examples thereof include staple foods such as bread and spaghetti, confectionery such as cookies, candy, gummy, and beverages such as juice and soft drinks. These manufacturing methods may be in accordance with ordinary manufacturing methods for foods.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to examples, but it goes without saying that the present invention is not limited to these examples. The phosphatidylcholinesterol acyltransferase activity promoters LCAT-1 and 2 described herein were prepared as described in Examples below.

Example 1 Candy Candy was prepared according to the following formulation. That is,
The component A was heated and melted at 150 ° C., cooled to 120 ° C., the component B was added, the mixture was stirred, and a uniform product was molded and cooled to obtain a candy. A sugar 59 parts by weight starch syrup 30 parts by weight B citric acid 1 part by weight LCAT-1 10 parts by weight

Example 2 Candy A candy was prepared according to the following formulation. That is,
The component A was heated and melted at 150 ° C., cooled to 120 ° C., the component B was added, the mixture was stirred, and a uniform product was molded and cooled to obtain a candy. A sugar 59 parts by weight starch syrup 30 parts by weight B citric acid 1 part by weight LCAT-2 10 parts by weight

(Example 3) Gummy A component is heated and dissolved at 110 ° C., B component separately swelled and dissolved is added, and further C component is poured and stirred, poured into a mold and left for one day and night, and then removed from the mold to remove the gummy. Obtained. A sugar 40 parts by weight starch syrup 40 parts by weight B gelatin 8 parts by weight water 5 parts by weight C citric acid 2 parts by weight LCAT-1 5 parts by weight

(Example 4) Gummies A component was heated and dissolved at 110 ° C., B component separately swollen and dissolved was added, and further C component was poured and stirred, poured into a mold and left for one day and night, and then removed from the mold to remove the gummy. Obtained. A sugar 40 parts by weight starch syrup 40 parts by weight B gelatin 8 parts by weight water 5 parts by weight C citric acid 2 parts by weight LCAT-2 5 parts by weight

Example 5 Bread Bread was prepared according to the following recipe. In other words, after weighing all the prescription ingredients, kneading them well, and carrying out primary fermentation at 40 ° C for 1 hour, a bench time of 15 minutes was taken and molded at 40 ° C.
Second fermentation was performed for 45 minutes, and baking was performed for 25 minutes while steaming in an oven at 230 ° C to obtain bread. Strong flour 500 parts by weight Dry yeast 10 parts by weight Melted butter 50 parts by weight Salt 8 parts by weight Sugar 15 parts by weight Warm water at 38 ° C 320 parts by weight LCAT-1 10 parts by weight LCAT-2 10 parts by weight

(Example 6) Granules Granules were prepared according to the following formulation. That is, the prescription ingredients were weighed, part A was put into a glad granulator, mixed at low speed, and granulated while spraying part B at high speed. This was blow-dried at 40 ° C. for 48 hours and sieved to obtain a granule. A crystalline cellulose 40 parts by weight lactose 40 parts by weight aluminum stearate 2 parts by weight hydroxypropylmethyl cellulose 8 parts by weight LCAT-1 10 parts by weight B 50% ethanol aqueous solution 20 parts by weight

(Example 7) Granules Granules were prepared according to the following formulation. That is, the prescription ingredients were weighed, part A was put into a glad granulator, mixed at low speed, and granulated while spraying part B at high speed. This was blow-dried at 40 ° C. for 48 hours and sieved to obtain a granule. A crystalline cellulose 40 parts by weight lactose 40 parts by weight aluminum stearate 2 parts by weight hydroxypropylmethyl cellulose 8 parts by weight LCAT-2 10 parts by weight B 50% ethanol aqueous solution 20 parts by weight

Example 8 Granules Granules were prepared according to the following formulation. That is, the prescription ingredients were weighed, part A was put into a glad granulator, mixed at low speed, and granulated while spraying part B at high speed. This was blow-dried at 40 ° C. for 48 hours and sieved to obtain a granule. A crystalline cellulose 40 parts by weight lactose 40 parts by weight aluminum stearate 2 parts by weight hydroxypropylmethylcellulose 8 parts by weight LCAT-1 5 parts by weight LCAT-2 5 parts by weight B 50% ethanol aqueous solution 20 parts by weight

Example 9 Granules Granules were prepared according to the following formulation. That is, the prescription ingredients were weighed, part A was put into a glad granulator, mixed at low speed, and granulated while spraying part B at high speed. This was blow-dried at 40 ° C. for 48 hours and sieved to obtain a granule. A Crystalline cellulose 40 parts by weight Lactose 40 parts by weight Aluminum stearate 2 parts by weight Hydroxypropyl methylcellulose 8 parts by weight LCAT-2 5 parts by weight Mevalotin 5 parts by weight B 50% ethanol aqueous solution 20 parts by weight

[0021]

【Example】

Example 1 Manufacturing Example 1 l of water was added to 100 g of the root bark of a button and the mixture was extracted while heating for 3 hours. After cooling, insoluble matter was removed by filtration and freeze-dried to obtain 40 g of a phosphatidylcholinesterol acyltransferase activity accelerating agent (LCAT-1). Disperse this in 500 ml of water and use DIAION HP
-20 (manufactured by Mitsubishi Kasei) is passed through a column filled with pure water,
A 20% aqueous ethanol solution and ethanol (3 L) were each flowed for fractionation. The 20% ethanol aqueous solution fraction was concentrated to obtain 4.2 g of a phosphatidylcholinesterol acyltransferase activity promoter (LCAT-2).

Example 2 Measurement of Phosphatidylcholine Sterol Acyltransferase Activity Based on the method described below, phosphatidylcholine of LCAT-1 and 2 which are phosphatidylcholine sterol acyltransferase activity promoters of the present invention was used. The sterol acyltransferase activity promoting action was measured. That is, 4 groups of 6 ICR-MCH male mice (7 weeks old) were prepared for each group, and the first group was bred by free ingestion of CE-2 manufactured by CLEA Japan, Inc. and water for 2 weeks. Groups 2 to 4 were fed with a mixed diet of CE- (80%) and lard (20%) (high lard diet) and water ad libitum, while the second group was fed with 0.1% CMC aqueous solution. , L for the third group
A 10% 0.1% CMC solution of CAT-1 and a 10% 0.1% CMC solution of LCAT-2 were administered to the fourth group at a dose of 0.5 ml / day / animal, respectively. After the experiment was completed, blood was collected from each animal, and the phosphatidylcholinesterol acyltransferase activity value (unit: unit) was measured using LCAT measurement kid manufactured by Nippon Shoji Co., Ltd. This kit measures phosphatidylcholinesterol acyltransferase activity by the reaction shown in Chemical formula 1. The results are shown in Table 1. From this, it is understood that the phosphatidylcholinesterol acyltransferase activity-promoting agent of the present invention has a phosphatidylcholinesterol acyltransferase activity-promoting activity.

[0023]

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[0024]

[Table 1]

[0025]

According to the present invention, a new phosphatidylcholinesterol acyltransferase activity promoter can be provided.

Claims (8)

[Claims] 1. A phosphatidylcholinesterol acyltransferase activity promoter comprising the essence of a plant belonging to the genus Button in the genus Buttonae. 2. The phosphatidylcholinesterol acyltransferase activity accelerating agent according to claim 1, wherein the plant of the genus Buttonae is a button. 3. The phosphatidylcholinesterol acyltransferase activity promoter according to claim 1, wherein the essence is a polar solvent extract or a solvent distillate thereof. 4. The phosphatidylcholinesterol acyltransferase activity promoter according to any one of claims 1 to 3, wherein the site of use of the plant is the root bark. 5. The root bark of a plant belonging to the genus Button in the genus Buttonae is extracted with boiling water, and this extract is adsorbed on Diaion HP-20 and eluted with ethanol or an ethanol-water mixture. The phosphatidylcholinesterol acyltransferase activity promoter according to any one of claims 1 to 4. 6. Treatment or prevention of hyperlipidemia due to imbalance of phosphatidylcholinesterol acyltransferase activity containing the phosphatidylcholinesterol acyltransferase activity promoter according to any one of claims 1 to 5. Composition. 7. The composition according to claim 6, wherein the form is food. 8. The composition according to claim 6, which is in the form of a drug.