JP2000044470A - Hyperlipemia medicine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hyperlipemia medicine suitable for self medication having a remarkable hyperlipemia treatment effect. SOLUTION: This hyperlipemia medicine contains eicosapentaenoic acid, docosahexaenoic acid or their ester derivatives as a component A and one or more kinds of substances selected from the group consisting of polyenephosphatidyl choline, soysterol, soybean oil non-saponified product, riboflavin, riboflavin lactate, panthenol and pantethine as a component B.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a hyperlipidemic drug. More specifically, eicosapentaenoic acid, docosahexaenoic acid or an ester derivative thereof as component A, and polyenephosphatidylcholine as component B,
The present invention relates to a hyperlipidemic drug comprising one or more selected from soysterol, unsaponifiable soybean oil, riboflavin, riboflavin butyrate, panthenol, and pantethine.

[0002]

2. Description of the Related Art Hyperlipidemia is well known as a serious cause of arteriosclerosis, and many drugs are used for its treatment. Most of these remedies are obtained through medical institutions under the control and prescription of doctors, and patients cannot freely purchase them at pharmacies and the like. Hyperlipidemia is roughly divided into hypercholesterolemia and hypertriglyceridemia. Few drugs have an effect on both hypercholesterolemia and hypertriglyceridemia. For example, eicosapentaenoic acid (EPA) and mevalotin are known. Therefore, in many cases, a plurality of drugs effective for hypercholesterolemia and hypertriglyceridemia are taken as needed.

[0003] On the other hand, hyperlipidemia is a disease in the field generally called "lifestyle-related disease", and the disease gradually progresses, and eventually leads to serious diseases such as myocardial infarction. have. Hyperlipidemia, a so-called “lifestyle-related disease,” can be considered a disease for which self-medication (self-medication) is effective, including prevention. However, there is no known hyperlipidemia drug that is effective and safe and can be used for both self-medication hypercholesterolemia and hypertriglyceridemia that can be freely purchased by patients and has a remarkable effect. (General Pharmaceutical Japan Pharmaceutical Collection 1998-99 edition Pharmaceutical Timeline). For example,
It is disclosed that EPA can be used for both hypercholesterolemia and hypertriglyceridemia (Japanese Patent Laid-Open No.
No. 6,122,312, JP-A-59-223807). However, the effect of EPA alone is not always sufficient. It is known that the B component polyenephosphatidylcholine, soysterol, unsaponifiable soybean oil, riboflavin, riboflavin butyrate, panthenol, and pantethine are effective for hypercholesterolemia (General Pharmaceutical Drugs 1998-99). Year Edition, pp. 341-434, Pharmaceutical Times). Regarding the safety data, among the A components, ethyl eicosapentaenoate had an LD ₅₀ of 20 g / oral when administered orally.
It is known to be over kg / day. In addition, L of the component B polyenephosphatidylcholine, soysterol, unsaponifiable soybean oil, riboflavin, riboflavin butyrate, panthenol and pantethine is administered orally to rats by oral administration.
D ₅₀ is as follows. Polyene phosphatidylcholine; 6 g / kg or more, soysterol; 8 g / kg or more, unsaponifiable soybean oil; 8 g / kg or more, riboflavin; 10 g / kg or more, riboflavin butyrate; 7.5 g / kg or more, panthenol; 7 g / kg Pantethine: 10 g / kg or more.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a hyperlipidemic drug which has both effects and safety and is suitable for self-medication.

[0005]

Means for Solving the Problems In view of the above problems, the present inventor has studied various drugs which are said to be effective for hyperlipidemia, and as a result, as a component A, a specific higher fatty acid or an ester derivative thereof. And the finding that when a specific compound is combined as the B component has a remarkable effect as a hyperlipidemic drug, the present invention has been completed. That is, the present invention
It is as follows. (1) As component A, eicosapentaenoic acid, docosahexaenoic acid or an ester derivative thereof, and as component B, polyenephosphatidylcholine, soysterol,
Unsaponifiable soybean oil, riboflavin, riboflavin butyrate,
A hyperlipidemic drug comprising one or more selected from the group consisting of panthenol and pantethine. (2) The hyperlipidemic drug wherein the ester derivative of eicosapentaenoic acid or docosahexaenoic acid is fish oil or liver oils. (3) The above-mentioned hyperlipidemia drug, wherein the liver oil is a vitamin A oil obtained by adding a liver oil to a vitamin A fatty acid ester.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION As the component A used in the present invention,
Higher fatty acids such as eicosapentaenoic acid (hereinafter abbreviated as EPA) and docosahexaenoic acid (hereinafter abbreviated as DHA) may be mentioned. In addition, ester derivatives of these EPA and DHA are mentioned. Examples of the ester derivatives of EPA and DHA include ethyl esters having 2 carbon atoms and glycerin esters. These A components may be used alone or in combination. These A components are:
Usually, fatty acids obtained by hydrolyzing fish oil or alkyl esters of fatty acids obtained by transesterifying fish oil with alcohol are used to concentrate and purify the product by distillation, urea addition, liquid chromatography, etc. Can be used. In the case of glycerin esters, purified fish oil obtained by purifying unpurified fish oil extracted from fish bodies by cooling fractionation, steam deodorization, activated clay treatment, or the like can be used. A refined fish oil is preferably mentioned from industrial availability. As the liver oil used as a raw material, a liver oil obtained by purifying crude liver oil extracted from cod or squid liver in the same manner as fish oil can be used. Furthermore, EPA,
As liver oils as glycerol esters of DHA, those known as vitamin A oils in terms of availability and stability, for example, those obtained by diluting retinol palmitate with purified liver oil can be used.

The eicosapentaenoic acid, docosahexaenoic acid or their ester derivatives as the component A are easily oxidized, and therefore, those to which a required amount of an antioxidant such as BHA, BHT and tocopherol is added may be used. .

The purity of eicosapentaenoic acid, docosahexaenoic acid or an ester derivative thereof used in the present invention is not particularly limited, but high purity is preferred from the viewpoint that a small dose is required.

The B component used in the present invention includes polyenephosphatidylcholine, soysterol, unsaponifiable soybean oil, riboflavin, riboflavin butyrate, panthenol and pantethine, and commercially available products can be used. Two or more of these B components can be used in combination.

The mixing ratio of the component A and the component B used in the present invention is 0.03 to 2500 in terms of A / B weight ratio.
The mixing ratio of the component A and the component B is 0.03 by weight ratio of A / B.
If the amount is less than that, it is difficult to exert the effect of the component A, which is not preferable. If the mixing ratio of the component A and the component B is more than 2,500 by weight of A / B, the effect of the component B becomes difficult to exert, which is not preferable. More preferably, it is 0.1 to 1000, still more preferably 0.5 to 100. Specifically, B
Although it depends on what the components are mixed with, for example, as the A component, based on the total amount of the EPA and DHA components, when the B component is polyenephosphatidylcholine, A / B is 0.03 to 3; 0.04 to 4; 0.04 to 4 for unsaponifiable soybean oil; 1 to 2500 for riboflavin; 0.4 to 1 for riboflavin butyrate
000; 1 to 1000 for panthenol; 0.08 to 170 for panthetin.

[0011] The dosage form of the hyperlipidemia drug of the present invention is not particularly limited as long as it is to be orally administered.
Tablets, powders, capsules and the like can be mentioned.

The hyperlipidemia drug of the present invention may be used as required in the above-mentioned dosage form, if necessary. For example,
Examples include gelatin, starch, cellulose, polyvinyl alcohol, lactose, calcium carbonate and the like.

The usage of the hyperlipidemia drug of the present invention depends on the mixing ratio of the component A and the component B. Usually, for an adult, 50 to 5000 mg / day, preferably 100 to
4000 mg / day, and as the B component, 2 to 1
It is preferably 500 mg / day, preferably 5 to 1000 mg / day.

[0014]

EFFECTS OF THE INVENTION The hyperlipidemic drug of the present invention comprises a component A, eicosapentaenoic acid, docosahexaenoic acid or an ester derivative thereof, which has been conventionally confirmed to be safe.
Contains at least one component selected from the group consisting of polyenephosphatidylcholine, soysterol, unsaponifiable soybean oil, riboflavin, riboflavin butyrate, pantothenic acid and pantethine, so that it can be used to treat hypercholesterolemia and hypertriglyceridemia. The effect is remarkably high.

[0015]

The present invention will be described in more detail with reference to specific examples. The percentages used are percentages by weight. Test Example 1 50 Wistar male 4-week-old rats were preliminarily reared for 1 week on a fish meal-free feed (AIN-93M manufactured by Oriental Yeast Co., Ltd.), and 10 of each were 1-A, 1-
B, 1-C, 1-D, and 1-E. Group A contains only fish meal-free feed, Group B contains cholesterol 1
%, Cholic acid 1%, lard 5%, fish meal free feed, group C cholesterol 1%, cholic acid 1
%, Lard 5%, and eicosapentaenoic acid ethyl ester (purity 93%) 0.6% blended fish meal-free feed. Group D contains cholesterol 1%, cholic acid 1%, lard 5%, polyenphosphatid. A diet containing no fish meal containing 0.6% of zircholine was added to group E. Cholesterol 1%, cholic acid 1%, lard 5%, eicosapentaenoic acid 0.3% and polyenphosphatidylcholine 0.3 were used.
% Of the feed without fish meal was ingested for 4 weeks. Four weeks after the start of administration, each animal group was fasted for 18 hours.
The abdomen was opened under anesthesia with intraperitoneal administration of pentobarbital sodium 30 mg / Kg, and whole blood was collected from the abdominal vena cava. The collected blood was centrifuged at 3000 rpm for 10 minutes to obtain plasma. As lipids in plasma, the amounts of triglycerides and total cholesterol were measured with an automatic biochemical analyzer (type 736-10, manufactured by Hitachi, Ltd.). The results are shown in Table 1.

[0016]

[Table 1]

Test Example 2 40 Wistar male 4-week-old rats were preliminarily reared for 1 week on a diet containing no fishmeal, and 10 of each were fed 2-
A, 2-B, 2-C, 2-D. Group A is a fish meal-free feed containing 1% cholesterol, 1% cholic acid and 5% lard, and Group B is a cholesterol 1 feed.
%, Cholic acid 1%, lard 5%, diet containing no fish meal containing 0.6% docosahexaenoic acid ethyl ester (purity 93%), group C cholesterol 1%, cholic acid 1%, lard 5% , A diet containing no fish meal containing 0.6% soysterol, cholesterol 1 in group D
%, Cholic acid 1%, lard 5%, docosahexaenoic acid 0.3% and soysterol-free diet were fed for 4 weeks each without fish meal. Four weeks after the start of administration, treatment was performed in the same manner as in Test Example 1, and the amounts of triglyceride and total cholesterol in plasma were measured. The results are shown in Table 1.

[0018]

[Table 2]

Test Example 3 Forty male Wistar rats of 4 weeks of age were preliminarily reared for 1 week on a diet containing no fish meal, and 10 of each rat were cultured for 3 weeks.
A, 3-B, 3-C, 3-D. Group A is a fish meal-free feed containing 1% cholesterol, 1% cholic acid and 5% lard, and Group B is a cholesterol 1 feed.
%, Cholic acid 1%, lard 5%, fish oil (containing 25% eicosapentaenoic acid and 12% docosahexaenoic acid).
A feed containing no fish meal containing 2%, a feed containing no fish meal containing 1% of cholesterol, 1% of cholic acid, 5% of lard, and 0.05% of riboflavin butyrate for group C, and a cholesterol of 1 for group D %, Cholic acid 1%, lard 5%,
Fish meal-free feeds containing 0.6% fish oil and 0.025% riboflavin butyrate were each ingested for 4 weeks. Four weeks after the start of administration, the cells were treated in the same manner as in Test Example 1, and the amounts of triglyceride and total cholesterol in plasma were measured. Table 3 shows the results.

[0020]

[Table 3]

Test Example 4 40 Wistar male 4-week-old rats were preliminarily reared for 1 week on a diet containing no fishmeal, and 10 of each were fed 4-
A, 4-B, 4-C, 4-D. Group A is a fish meal-free feed containing 1% cholesterol, 1% cholic acid and 5% lard, and Group B is a cholesterol 1 feed.
%, Cholic acid 1%, lard 5%, liver oil (eicosapentaenoic acid 15%, docosahexaenoic acid 20%, vitamin A
A diet containing no fish meal, containing 1.2% of 2000 IU), C group 1%, cholic acid 1%,
5% lard, 0.1% pantethine-free fish meal-free feed, group D cholesterol 1%, cholic acid 1
%, Lard 5%, liver oil 0.6% and pantethine 0.05
% Of the feed without fish meal was ingested for 4 weeks. Four weeks after the start of the administration, treatment was performed in the same manner as in Test Example 1, and the amounts of triglyceride and total cholesterol in plasma were measured. Table 4 shows the results.

[0022]

[Table 4]

TEST EXAMPLE 5 Forty male 4-week-old rats of the Wistar strain were preliminarily reared for 1 week on a diet containing no fish meal, and 10 of them were each fed to
A, 5-B, 5-C and 5-D. Group A is a fish meal-free feed containing 1% cholesterol, 1% cholic acid and 5% lard, and Group B is a cholesterol 1 feed.
%, Cholic acid 1%, lard 5%, vitamin A oil (containing 20% eicosapentaenoic acid, 15% docosahexaenoic acid, and 1.2% vitamin A) and a fish meal-free feed containing 1.2%, cholesterol 1 group C %, Cholic acid 1%, lard 5%, diet containing no fish meal containing 0.6% soybean oil unsaponifiable, group D cholesterol 1%, cholic acid 1%, lard 5%, vitamin A oil 0.6
% And 0.3% soybean oil unsaponifiables were fed for 4 weeks each without fish meal. Four weeks after the start of the administration, treatment was performed in the same manner as in Test Example 1, and the amounts of triglyceride and total cholesterol in plasma were measured. Table 5 shows the results.

[0024]

[Table 5]

From the above results, groups 1-E of test example 1, group 2-D of test example 2, group 3-D of test example 3, and test example 4 which are combinations of components A and B of the present invention. A 4-D group,
It can be seen that the 5-D group of Test Example 5 has a remarkable effect of lowering the amounts of triglyceride and total cholesterol in plasma, as compared with the case of using the component A or the component B alone.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/56 A61K 31/56 31/66 31/66 35/60 101 35/60 101 35/78 35 / 78 J F term (reference) 4C086 AA01 AA02 CB09 DA08 DA41 GA17 MA02 MA03 MA04 MA07 MA09 MA10 NA05 ZA45 ZC23 ZC33 ZC75 4C087 AA01 AA02 BB29 BB30 CA19 MA02 NA05 ZA45 ZC23 ZC33 ZC75 4C088 Z01A03 Z0418 CA09 DA05 DB09 GA05 JA63 KA18 MA02 MA03 MA04 MA17 MA21 MA24 NA05 ZA45 ZC23 ZC33 ZC75

Claims (3)

[Claims] (1) The component A is composed of eicosapentaenoic acid, docosahexaenoic acid or an ester derivative thereof and the component B is polyenephosphatidylcholine, soysterol, unsaponifiable soybean oil, riboflavin, riboflavin butyrate, panthenol and pantethine. A hyperlipidemia drug containing at least one selected from the group consisting of: 2. The hyperlipidemic agent according to claim 1, wherein the ester derivative of eicosapentaenoic acid or docosahexaenoic acid is fish oil or liver oils. 3. The hyperlipidemic agent according to claim 2, wherein the liver oil is a vitamin A oil obtained by adding a liver oil to a vitamin A fatty acid ester.