JPS63280023A - Antirheumatic - Google Patents

Abstract

PURPOSE:To obtain an antirheumatic agent with actions to inactivate rheumatic factors and inhibit collagen-inducing arthritis, by using L-cysteine ethyl ester or its acid adduct as an active ingredient. CONSTITUTION:The objective preparation is obtained by using L-cysteine ethyl ester or its acid adduct as an active ingredient, and mixing it with a carrier, an excipient, a diluent or other additives and subjecting the mixture to medicine preparation. For example, it is converted into tablets and given orally. The dose is 100-500mg/kg body weight of adults/day and given in portions. Or it is prepared into enteric tablets to avoid unpleasant eructation after administration. Further, the sugar-coated tablets are prepared to mask the bad smell of the ingredient.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to medicine, particularly antirheumatic medicine.

[Conventional technology]

L-cysteine ethyl ester hydrochloride has mucolytic action,
It has a ciliary movement-promoting effect and is widely used for acute and chronic bronchitis, expectoration when it is difficult to eject after surgery, and drainage of chronic sinusitis (Pharmacology and Treatment Vol. 6, No. 36)
57 pages 1978).

By the way, rheumatic diseases, particularly rheumatoid arthritis, are known to be stubborn and intractable systemic diseases whose symptoms repeat aggravation and remission over a long period of time. Aspirin, nonsteroidal anti-inflammatory drugs, corticosteroids, combination drugs, D-penicillamine, immunosuppressants, and immunomodulators are currently used as drug treatments for this disease (Orthopedic Surgery MOOK Na37, pages 5-19) 1
984).

[Problem that the invention seeks to solve]

In the drug treatment of rheumatism, non-steroidal anti-inflammatory drugs are most widely used, and immunosuppressants and immunomodulators are also attracting attention due to advances in immunology.

However, these drug treatments are symptomatic treatments and not fundamental treatments; non-steroidal anti-inflammatory drugs can cause side effects such as gastrointestinal disorders; and in some cases, immunological agents such as immunosuppressants and immunomodulators may also cause side effects. It has had problems such as the occurrence of serious side effects, and even now,
The development of effective drugs is desired.

(Means for Solving the Problems) In view of these circumstances, the present inventors have conducted intensive research with the aim of developing a useful anti-rheumatic drug, and as a result, have found that:
The inventors have discovered that a compound already widely used as a drug exhibits excellent antirheumatic effects, leading to the completion of the present invention.

The present invention relates to an antirheumatic drug characterized by containing L-cysteine ethyl ester or a pharmaceutically acceptable acid addition salt thereof as an active ingredient.

Acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, phosphate, nitrate, sulfate, or maleate, succinate, citrate, tartrate, p-)luenesulfonate. , organic acid salts such as vamoate.

As the active ingredient compound of the present invention, especially cysteine ethyl ester hydrochloride is used.

The antirheumatic drug of the present invention is an active ingredient compound itself,
Alternatively, it can be mixed with pharmaceutically acceptable additives such as carriers, excipients, and diluents, as appropriate, to form a tablet or the like, which can be safely administered to patients. The dosage may vary depending on the symptoms, patient's age, body weight, etc., but it is usually about 100 to about 500 av/kg per day for adults when administered orally.
This can be taken once or in divided doses.

[For production]

As shown in the following experimental examples, the active ingredient compound of the present invention has a rheumatoid factor inactivating effect and a collagen-induced arthritis suppressing effect, and is useful as an anti-rheumatic drug.

Experimental Example 1 Rheumatoid factor inactivation effect Commercially available rheumatoid factor test kit (RF latex (KW
), Nippon Freeze-Drying Research Co., Ltd.) according to the method of Itozai et al. (Japanese Pharmacological Journal, Vol. 76, p. 117, 1980). That is, rheumatoid factor positive serum was mixed with an equal volume of a physiological saline solution of a test compound, and reacted at 37°C. The reaction solution was collected over time and aggregation reaction was performed using latex. Agglutination was visually judged and evaluated into four levels: positive, weakly positive, false positive, and negative.

L-cysteine ethyl ester hydrochloride exhibited a rheumatoid factor negativity effect after 1 hour of reaction at a concentration of 10-''M.

Experimental Example 2 Collagen-induced arthritis suppressive effect Type II collagen was prepared by the method of Trentham et al.
J, Exp, Mad, No. 146S No. 857 p. 19
(1977). Group of 7 male Sprags
Using a Dawley raft (approximately 200 g in weight), 1 ml of collagen emulsion (2 mL/ml O, 1:1 emulsion of 1 N acetic acid and Freund's incomplete adjuvant) was applied to the skin of the back after hair removal under ether anesthesia. was administered in 5 divided doses, and 7 days later, 0.2n+1 of the same emulsion was administered to the ridge. The test compound was dissolved in 0.5% methylcellulose solution, and the test compound was dissolved in a 0.5% methylcellulose solution and
The mice were orally administered at a dose of 5 ml per kg of body weight once a day. Constant volumes were measured on the 21st and 28th days after sensitization using a digital volume meter (manufactured by Kukai Kikai), and the inhibition rate relative to the control group was determined.

When 100 μ/kg of L-cysteine ethyl ester hydrochloride was orally administered, the inhibition rate on the 21st day was 49.1%, and the inhibition rate on the 28th day was 42.3%.

The LDso value of acutely toxic L-cysteine ethyl ester hydrochloride when administered orally to male mice is 3470 ■/kg.

〔Example〕

Examples of formulations of the antirheumatic drug of the present invention will be given below as examples, but the present invention is not limited thereto.

■, Prescription (1 tablet 300qr) (i) Base tablet L-cysteine ethyl ester hydrochloride 100.0■ Crystalline cellulose 17.0 ■ Corn starch 10.0 ■ Ethyl cellulose
2.0 stearin magnesium 1.0 ■
(130,0 ■) (ii) Enteric film coating hydroxypropyl methyl cellulose phthalate 5.0 ■ Acetylated monoglyceride 0.5 *Talc
0.5 mg (6,0 ■) (iii) 11 Coating White I! 108.5 ■ Gum Arabic 3.0 ■ Gelatin
1.0 ■ Talc
30. O Titanium oxide
1.5■Triphosphorus Calcium 20.0■(1
64.0■) Total 300.0■ ■, Production method Take L-cysteine ethyl ester hydrochloride, crystalline cellulose and corn starch, knead and granulate using an alcoholic solution of 5% ethyl cellulose, and reduce the moisture content at 50°C. Dry until it becomes 1.5% or less. Mix magnesium stearate and use a pestle with a diameter of 7 to make 1 tablet 130
■Make the basic lock. 6 enteric coated tablets
■Make it into sugar-coated tablets using white sugar, gum arabic, etc. according to the usual method.

Enteric-coated tablets prevent unpleasant eructation after taking the drug, and sugar-coated tablets mask the unique odor of the drug substance.

〔Effect of the invention〕

As is clear from the description of the specification including the experimental examples and examples described above, the active ingredient compound of the present invention exhibits excellent antirheumatic effects and can be used as a therapeutic agent for various rheumatic diseases including rheumatoid arthritis.

Claims (1)

[Claims] An antirheumatic drug characterized by containing L-cysteine ethyl ester or a pharmaceutically acceptable acid addition salt thereof as an active ingredient.