JPH0692308B2 - Antihyperlipidemic agent - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel antihyperlipidemic agent containing a chitin oligomer and / or a chitosan oligomer as an active ingredient.

(Conventional Technology) Conventionally, hyperlipidemia (hypercholesterolemia, hypertriglyceridemia) has been considered as one of the causes of hypertension, arteriosclerosis, etc., and treatment and prevention of this hyperlipidemia. Therefore, many antihyperlipidemic agents have been developed, and for example, clofibrate, nicomol and the like are put to practical use.

(Problems to be Solved by the Invention) However, side effects such as muscular pain, headache, and redness of the skin for clofibrate, and rash, flushing of the face, gastrointestinal disorders, etc. for nicomol are known. A lipemic agent is desired.

(Means for Solving Problems) As a result of intensive studies conducted by the present inventors to provide an antihyperlipidemic agent with few side effects, the present inventors have found that it is a constituent component of the living cell wall present in the shell of crabs and the like. Chitin oligomers (also referred to as N-acetylchitooligosaccharides) and chitosan oligomers (also referred to as chitooligosaccharides), which are known substances obtained by hydrolyzing chitin, have surprisingly excellent antihyperlipidemic activity and antihyperlipidemia. The inventors have found that they have excellent properties as a blood sugar agent, and have completed the present invention.

The antihyperlipidemic agent of the present invention contains at least one substance selected from chitin oligomers and chitosan oligomers as an active ingredient. Specific examples of the chitin oligomer used as an active ingredient include di-N-acetyl-
Chitobiose, tri-N-acetyl-chitotriose,
Tetra-N-acetyl-chitotetraose, penta-N
-Acetyl-chitopentaose, hexa-N-acetyl-chitohexaose, hepta-N-acetyl-chitoheptaose, and specific examples of the chitosan oligomer include chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose. Examples thereof include aus and chitoheptaose.

The antihyperlipidemic agent of the present invention is prepared by mixing at least one of chitin oligomer and chitosan oligomer with a known pharmaceutically acceptable liquid or solid carrier by a conventional method, and if necessary, a solvent, a dispersant or an emulsifier. , Buffers, stabilizers,
Formulated into tablets, granules, powders, powders, capsules, syrups, solutions, injections, etc. by adding excipients, binders, disintegrants, lubricants, etc., and administered orally or parenterally can do.

The daily dose of the active ingredient of the antihyperlipidemic agent of the present invention for an adult is 0.1 to 10 g, preferably 0.1 to 3 g per kg body weight.

(Operation and Effect of the Present Invention) The antihyperlipidemic agent of the present invention is a known substance obtained by hydrolyzing chitin, which is a constituent component of a living cell wall present in the shells of crabs and the like, of chitin oligomer and chitosan oligomer. Since it contains at least one active ingredient, it has very little toxicity and side effects to the human body and is extremely safe, and the chitin oligomer and chitosan oligomer are water-soluble, so formulation and administration are simple and effective. It has excellent advantages such as rapid onset.

(Example) Formulation Example 1 Tablet A tablet having the following composition was prepared by a conventional method.

Hexa-N-acetylchitohexaose 20 mg Lactose 60 mg Potato starch 30 mg Polyvinyl alcohol 2 mg Magnesium stearate 1 mg Tar dye Small amount Formulation Example 2 Powder A powder having the following composition was prepared by a conventional method.

Chitohexaose 20 mg Lactose 280 mg Formulation Example 3 Solution A solution having the following composition was prepared by a conventional method.

Hexa-N-acetyl 10 g Chitohexaose Injectable saline 1000 ml Test Example ddY Slc 4-week-old male mice (6 to 7 mice per group, average weight about 18)
g) is a commercially available feed F-2 for mice, rats and hamsters
After breeding for 3 days (manufactured by Funabashi Farm Co., Ltd., hereinafter referred to as "standard diet"), they were fed for 5 days on a high-cholesterol diet having the composition shown in Table 2. The average weight of the mice at this time was about 25 g.

Then, a solution containing a chitin oligomer or chitosan oligomer as an active ingredient prepared according to Formulation Example 3 while being fed with the above high-cholesterol diet for 2 days at a dose of 240 mg / kg of the active ingredient per dose for 2 days. Administered directly to the stomach by oral sonde twice in total. On the day after the final administration, that is, on the 11th day of breeding, about 1 ml of blood was collected from the mouse and cholesterol in serum was quantified by the Zurkowski direct method to inhibit cholesterol. I asked. still,
The test was conducted using a group fed with a standard diet alone for 10 days without administration of chitin oligomer and chitosan oligomer as a standard diet group, a group fed with a standard diet for 3 days and then a high cholesterol diet for 7 days as a control group.

The cholesterol inhibition rate was calculated by the following formula.

The obtained results are shown in Tables 3 and 4.

Table 1 Standard food composition (% by weight) General ingredients Water …… 7.0% Crude protein …… 24.5% Crude fat …… 4.4% Crude fiber …… 3.6% Crude ash …… 5.5% Soluble nitrogen-free material …… 55.0% Total energy …… 4.28Kcal / g Metabolic energy …… 3.85Kcal / g Digestible crude protein …… 22.46% (It also contains necessary minerals, vitamins and amino acids.) Table 2 High cholesterol diet composition (% By weight) Sucrose …… 15.0% Dietary salt …… 2.0% Coconut oil …… 10.0% Cholesterol …… 0.6% Cholic acid …… 0.2% Choline chloride …… 0.3% Standard diet …… 71.9%

Claims (1)

[Claims] 1. An antihyperlipidemic agent comprising a chitin oligomer and / or a chitosan oligomer as an active ingredient.