JPS59196818A - Remedy for nephritis - Google Patents

Abstract

PURPOSE:A remedy for nephritis, containing at least one of specific benzaldehyde derivative as an active constituent, and capable of inhibiting glomerular nephritis. CONSTITUTION:A remedy for nephritis, containing at least one of a benzaldehyde drivative expressed by the formula (m is an integer 2 or 3) as an active constituent. The compound expressed by the formula is well known as a carcinostatic agent and colorant for human hair, but is newly found to have inhibitory action on glomerular nephritis and effective as a remedy for the nephritis. The compound expressed by the formula together with a pharmaceutically acceptable carrier or adjuvant may be administered as a composition in the form of various pharmaceuticals by oral or parenteral routes. But the oral administration is preferred. The oral dose thereof is 0.1-500mg/kg/day, preferably 0.5-200mg/kg/ day. The compound expressed by the formula has low toxicity and improved inhibitory action on proliferative glomerular nephritis, etc.

Description

Detailed Description of the Invention The present invention provides a treatment for nephritis containing at least one noodle of a benzaldehyde derivative represented by the general formula (011)n (wherein n represents an integer of 2 or 3) as an active ingredient. Regarding therapeutic agents.

Penzaldehyde F, A, which is represented by the general formula (1), is a known substance Jft that exists in various edible plants, and is used as an anticancer agent (Japanese Patent Laid-Open No. 56-57712) or for hair coloring (Japanese Patent Laid-Open No. 56-57712). 57-31.606). However, no reports have been found regarding the inhibitory effect of the above-mentioned benzaldehyde derivatives on glomerulonephritis. The present inventors have perfected the effect of the benzaldehyde derivative represented by the general formula (1) (hereinafter referred to as the 9-chain of the present invention) on moxibustion. Suppresses glomerulonephritis caused by
and discovered that it is a drug for treating nephritis.
This resulted in a misfire 8JJ.

Based on the findings in Section 1, the present invention provides a therapeutic agent for 'f'i inflammation, which uses the present invention a alone or as an active ingredient of a pharmaceutical composition.

All of the uninvented substances have low toxicity and have an inhibitory effect on nephritis, as described below.

The substance of the present invention can be administered orally, enterally, or by injection in various formulations as a composition together with a pharmaceutically acceptable carrier and/or adjuvant. In this case, the compounds of the present invention may be used in combination of 26 or more, or may be used in combination with other pharmaceutically active substances. At this time, in order to improve the irritation of the substance of the present invention, the substance of the present invention may be made into an clathrate compound using a compound with inclusion ability such as cyclodextrin, or may be mixed with various amines, amino acids, or sugars, or It is also effective to use it as a condensate.

Since the substance of the present invention can be applied orally or parenterally,
They may take any form suitable for their administration. Furthermore, the substance of the present invention can be provided in dosage unit form, such as powders, granules, tablets, dragees, capsules, suppositories, suspensions, solutions, emulsions, ampoules, injections, etc., if they contain an effective vehicle. You can get various forms of.

Therefore, it should be understood that the medicament of the present invention can be prepared by applying any conventionally known formulation means. The content of the substance of the present invention (active ingredient) in the preparation of the present invention is 0.01 to 100%, preferably 0.1 to 100%.
Can be adjusted over a wide range of 70% (weight).

As mentioned above, the drug of the present invention can be administered orally or parenterally to humans and animals, but oral administration is particularly preferred. In this case, oral administration also includes sublingual administration), and non-oral administration includes subcutaneous, intramuscular, intravenous, etc. injections and infusions.

The dose of the drug of the present invention depends on whether the subject is an animal or a human, and is influenced by age, individual differences, medical conditions, etc. In some cases, doses outside the following range may be administered; however, in general, when administering to humans, , the oral dose of the substance of the present invention is 1 kg body weight.
, daily allowance 901-500~, preferably 0.5-200
■ Parenteral dosage: 1 kg body weight, daily dose
0.01-200 Ff, preferably 01-110
Administer 07n in 1 to 4 divided doses.

Hereinafter, the toxicological and morbid properties of the substance of the present invention will be explained using representative compounds.

1. Oral and intraperitoneal administration of 3.4-dihydroxybenzaldehyl 1:' using acutely toxic female JCL-ICR mice/j
I was able to row the pre-acute a in the route. Oral administration: 0.2%
For intraperitoneal administration, the CJVjCVCfB dispersion was dissolved in physiological saline and adjusted to a predetermined amount using a gastric tube or syringe.

After the administration, we continued to observe the symptoms and calculated the mortality rate over time for up to 7 days, and determined the LD5. The value of fCo is calculated and the results are shown in Table 1.

As a result of conducting toxicity tests on 2,5-dihydroxybenzaldehyde F and 3,4,5-trihydroxybenzaldehyde in the same manner as in (a) in Table 1), oral LD SOIL was 500 rrq/ It was more than kg.

2. Pharmacological properties 1) MRL/l mice are animals that spontaneously develop autoimmune abnormalities, exhibit SLE-like lesions, and spontaneously develop arthritis and proliferative glomerulonephritis. Clinically, the mouse exhibited severe proteinuria due to kidney damage, and the mouse's lifespan was shortened to 4-t, leading to death. (EXp, Animal.

(2), 161-172.1981) Male MR of the substance of the present invention (3,4-dihydroxybenzaldehydone)
It was orally administered to L/l mice, and kidney tissues were removed at 24 weeks of age, and lesions were pathologically measured using a light microscope, an electron microscope, and a fluorescent antibody method.

The test system was administered as an aqueous solution of mulberry p25 da/kg to 5-week-old mice once a day. Ten animals were used in each of the treated group and untreated group. Table 2 shows the renal pathological test results. The non-medicated group (control) showed diffuse proliferative glomerulonephritis accompanied by thickening of the glomerular basement membrane, but the test drug-administered group showed suppression of renal lesions, immune complex deposition, and glomerular base. Suppression of proliferative nephritis in membranes, etc. was observed.Also, clinically, a decrease in urinary protein ν was observed.

In addition, proliferative nephritis was suppressed as a result of oral administration of the substances of the present invention, 2,5-dihydroxybenzaltehyde and 3,4,5-trihydroxybenzaldehyde, to fvJRL/l mice in the same manner as above. There was found.

2) Bovine face albumin (BS) was administered to male rabbits weighing 2 to 3 kg.
When the 1-T saline in A) is injected into the ear vein once a day, severe proteinuria occurs and glomerulonephritis develops. or,
A suspension of the substance of the present invention was prepared in the same manner as in 1) above in a dosage of 10,071 ml.
9. The kidneys were exposed to sunlight once a day, and 3 months later, the kidneys were dissected and the kidney λiL was determined. υ lesions were measured using a microscopic microscope and a fluorescent antibody method, and 5 chickens were used for each of the present invention f (administered?E') and non-administered group (only the solvent was administered), The results are shown in Table 3. In the iτvhe-6 light substance administration group, suppression of the amount of protein in the urine and suppression of serum urea nitrogen (serum urea nitrogen) was observed, as well as suppression of renal lesions. Precipitation of immune complexes in glomeruli and suppression of proliferative glomerulonephritis were observed.

From the results shown in Table 3 (Table 1), it can be seen that the substance of the present invention has an excellent suppressive effect on proliferative glomerulonephritis. Therefore, the substance of the present invention has extremely useful uses as a therapeutic agent for nephritis.

A specific example of formulation of the mulberry agent of the present invention will be shown below as an example. SJ: Capital in Examples: i Indicates offshore amount unless otherwise specified.

Example 1 Substance of the present invention (3,4-,7-translated/noλdehyF)2
Add 3 parts glucose, 95 parts physiological saline, mix with heating, and sterilize to prepare an injection.

Example 2 Inventive product i (2,4,6-trihydroxybenzaldehyde) 10 parts heavy magnesium oxide
15 parts lactose
Mix 75 parts uniformly to form a powder or granular powder.

Also, this powder is put into a capsule container to form a capsule.

Claims (1)

[Claims] (1) 11 anti-inflammatory agent containing at least one benzaldehyde derivative represented by the general formula (1) (% formula %) (wherein n represents an integer of 2 or 3) as an active ingredient.