JP2872695B2 - Nephritis treatment - Google Patents

Description

The present invention relates to a medicament containing sulfonoglycolipid or a pharmaceutically acceptable salt thereof as an active ingredient. More specifically, the present invention relates to a therapeutic agent for nephritis comprising sulfonoglycolipid or a pharmaceutically acceptable salt thereof as an active ingredient.

[Background of the invention, prior art]

Nephritis includes acute nephritis, chronic nephritis and the like. Generally, it refers to a state in which renal function is reduced due to the kidney itself or a cause other than the kidney. Various drugs are used for the treatment of these nephritis, but there is no definitive drug.

In view of such circumstances, the present inventors have intensively studied for many years to develop a new therapeutic agent for nephritis, and as shown below, have found that sulfonoglycolipid is effective as a therapeutic agent for nephritis. I found it.

[Structure and effect of the invention]

The active ingredient of the present invention is a sulfonoglycolipid represented by the following chemical structural formula (I) or a pharmacologically acceptable salt thereof.

Sulfonoglycolipid is a compound having the above chemical structural formula, and is described, for example, in the following literature. That is, AABenson et al.,
Proc. NAS Vol. 45, 1582 to 1587 (1959), and the extraction method from sponge is described in H. Kikuchi et al., Chem. Ph.
arm.Bull., Vol. 30, 3544-3547 (1982), and further described on Roy Gigg et al., JCSPerkin.
I, 2490-2493 (1980).

Although the sulfonoglycolipid has a stereoisomer with respect to the glycerin side chain as apparent from the chemical structural formula, in the present invention, the RS produced by the synthetic method is used.
It may be a body, an S body, or an R body.

In the above chemical structural formula, Is an expression including any of the above-mentioned RS-form, S-form, and R-form.

The RS isomer is synthesized, for example, according to the above-mentioned literature.
In order to obtain a body and an S body, the RS body is divided by a conventional method.

The above compounds can be collected in free or salt form. Preferred as salt forms are pharmaceutically acceptable salts such as, for example, potassium, calcium, triethylamine, tris (hydroxymethyl) aminomethane, more preferably sodium.

Next, pharmacological experimental examples will be described in order to explain the effects of the compound of the present invention in detail.

Pharmacological Experimental Example 1 Effect on Heymann Nephritis For the test, male Fischer rats weighing 90 to 110 g are used. Edington's method [Edgington TSet a
l., J. Exp. Med., 127, 555 (1968)], and 0.5 ml of antiserum obtained by sensitizing rabbits with the tubular brush border antigen prepared intraperitoneally. 1 minute before, the compound of the present invention (RS form) was intravenously administered at a dose of 100 or 200 mg / kg (using a physiological saline solution as a control), and urine was collected for 1 day from 5 days after administration of the antiserum. The amount of urine protein is measured by determining how small the amount of urine protein is compared with the control group.
Urine protein was determined by colorimetry using BSA as a control [Bradford, MM
l., Anal. Biochem., 72, 248 (1976)].
Table 1 shows the obtained results.

As is clear from Table 1, the compound of the present invention suppresses an increase in urine protein in Hyman nephritis.

From the above pharmacological experimental examples, it can be seen that the compound of the present invention, sulfonoglycolipid, is effective in treating and preventing nephritis.

When a toxicity test of the compound of the present invention was performed by intravenous administration using male ddy mice (body weight: 20 to 30 g), no death was observed at 200 mg / kg, and thus the compound of the present invention is highly safe.

When the compound of the present invention is used as a therapeutic agent for nephritis, it is administered orally or parenterally (intramuscularly or subcutaneously intravenously. The dose varies depending on the disease, degree of symptoms, age of patient, health of patient). The condition, body weight, if there is simultaneous treatment, the type, frequency of treatment, the nature of the desired effect and the like are not particularly limited, but are orally about 1 mg to 200 mg, preferably about 5 mg to 50 mg, more preferably, orally per adult day. Is administered about 5 mg to 15 mg once or more times a day, and about 0.01 mg / kg to 1 mg for injections.
/ kg, preferably about 0.03 mg / kg to 0.1 mg / kg.

Examples of the dosage form include powders, fine granules, granules, tablets, capsules, suppositories, injections and the like. At the time of formulation, it is manufactured by an ordinary method using a usual formulation carrier.

That is, when adjusting the solid preparation for oral use, after adding an excipient to the base drug, and further, if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, and the like, a tablet, Coated tablets, granules, tablets, capsules, etc.

As excipients, for example, lactose, corn starch, sucrose, glucose, sorbitol, crystalline cellulose, silicon dioxide, etc., as binders, for example, polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, shellac, Hydroxypropyl cellulose, hydroxypropyl starch, polyvinylpyrrolidone, etc., as disintegrants, for example, starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, calcium citrate, dextrin, pectin, etc., as lubricants For example, magnesium stearate, talc, polyethylene glycol, silica, hydrogenated vegetable oils, etc., are permitted to be added to pharmaceuticals as coloring agents, but as flavoring agents Include cocoa powder, menthol, aromatic acid, peppermint oil, borneol, cinnamon powder and the like are used. Of course, these tablets and granules may be sugar-coated, gelatin-coated and optionally coated as needed.

When preparing an injection, a pH adjuster, a buffer, a stabilizing agent, a solubilizing agent, and the like are added to the main drug, if necessary, to give an intravenous injection by a conventional method.

────────────────────────────────────────────────── ─── Continued on the front page (72) Yoshitake Ogata, Inventor 1-10-7, Akubo, Tsukuba, Ibaraki Prefecture (72) Inventor, Shin Shin Ikeda 2-19-8, Umezono, Tsukuba, Ibaraki Prefecture (58) Field surveyed (Int .Cl. ⁶ , DB name) A61K 31/70 C07H 15/04 CA (STN) REGISTRY (STN) MEDLINE (STN)

Claims (1)

(57) [Claims] 1. The following chemical structural formula A therapeutic agent for nephritis comprising, as an active ingredient, a sulfonoglycolipid represented by the formula: or a pharmaceutically acceptable salt thereof.