JP3032315B2 - Fatty liver treatment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a therapeutic agent for fatty liver containing tauroursodeoxycholic acid as an active ingredient.

[0002] Tauroursodeoxycholic acid is a compound represented by the following chemical formula.

[0003]

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[0004]

2. Description of the Related Art Fatty liver is a condition in which the liver cells are mainly filled with neutral fat, and fat droplets in the liver cells compress intracellular organelles, resulting in abnormal function. In addition, swelled hepatocytes containing fat droplets or two hepatocytes adjacent to each other fuse to form one large swelling, which may compress the sinusoids and hinder blood flow. The pathogenesis is overnutrition, diabetic, alcoholic, and drug-related, but in any case, it is considered to be closely related to abnormal lipid metabolism mainly in the liver. At present, few effective treatments are known.

[0005]

SUMMARY OF THE INVENTION The present inventor has studied the effects of various bile acid compounds on liver diseases for many years, and found that tauroursodeoxycholic acid is effective for fatty liver. Reached.

[0006]

According to the present invention, there is provided a therapeutic agent for fatty liver containing tauroursodeoxycholic acid as an active ingredient.

[0007] Tauroursodeoxycholic acid used in the present invention can be produced using ursodeoxycholic acid as a raw material by a known production method for a taurine conjugate of bile acid. In the present invention, it goes without saying that commercially available tauroursodeoxycholic acid can be used.

The results of the liver function improving effect of tauroursodeoxycholic acid in a clinical test are described in detail below.

[0009] Tauroursodeoxycholic acid was administered to 6 volunteers diagnosed with fatty liver for 1 week for 2 weeks.
It was orally administered 700 mg daily. Before and after the test was performed, blood collected from a vein was centrifuged to collect serum. GOT (Karm) was performed on the obtained serum using Centrific Chem 600 (manufactured by Barker) as a biochemical test.
en method) and GPT (Wrobleski & L)
adue method) values were measured. The results are shown in Table 1.

[0010]

[Table 1]

[0011] In all cases, liver function was improved.

Further, in some cases, GOT and GPT were measured after the administration of tauroursodeoxycholic acid was continued for 4 months. Abdominal CT values (unit: HU) were also measured by an image diagnosis (Somaton Plus, manufactured by Seimens Instruments; measurement condition window value: 50, window width: 200) representing fat mass, and the results are shown in Table 2.

[0013]

[Table 2]

[0014] Improvement of liver function and reduction of hepatic fat mass were observed by long-term continuous administration of tauroursodeoxycholic acid.

As is clear from Tables 1 and 2, tauroursodeoxycholic acid was found to have a remarkable liver function-improving effect and lipid-lowering effect, indicating that it is useful for fatty liver.

The acute toxicity test is described below. Using 5-week-old male ddY mice and male Sprague-Dawley rats, the acute toxicity (LD50) of tauroursodeoxycholic acid was measured. LD50 is at least 6.0 / kg orally in mice and 350 mg / kg intravenously.
That was all. In rats, the dose was 5.0 g / kg or more orally and 300 mg / kg or more intravenously.

In view of the above tests, a drug containing tauroursodeoxycholic acid as an active ingredient can be said to be a therapeutic agent for fatty liver by improving lipid metabolism mainly in the liver.

The dose of tauroursodeoxycholic acid to a patient varies depending on age, symptoms and the like, but is generally 20 to 2000 mg, preferably 5 to 500 mg orally per day for an adult.
It is preferable to use 0 to 1500 mg, 10 to 1000 mg by intravenous injection, preferably 20 to 600 mg, and to use them in 1 to 6 times, preferably 1 to 3 times.

The therapeutic agent for fatty liver of the present invention contains various solid or liquid preparation carriers which are physiologically harmless to the active ingredient tauroursodeoxycholic acid within a range capable of maintaining the above-mentioned daily dose. Pharmaceutical compositions are also included. The pharmaceutical composition can be in the form of tablets, capsules, powders, fine granules, granules, solutions, syrups, suspensions, emulsions or injections.

The pharmaceutical carrier may be any of those usually used in such forms. Various excipients, binders, disintegrants, lubricants, coating agents, solubilizing agents, emulsifiers, suspending agents,
Stabilizers or solvents are mentioned.

[0021]

As described above, tauroursodeoxycholic acid has a liver function improving effect and a lipid lowering effect, and thus can be said to be a useful therapeutic agent for fatty liver.

Claims (1)

(57) [Claims] 1. A therapeutic agent for fatty liver containing tauroursodeoxycholic acid as an active ingredient