JPS60209532A - Remedy for juvenile pheumatoid arthritis - Google Patents

Abstract

PURPOSE:To provide a remedy for juvenile rheumatoid arthritis for intravenous injection, containing a sulfonate immunoglobulin as an active component, and having remarkable effect for the improvement of the clinical symptoms. CONSTITUTION:The objective remedy for juvenile rheumatoid arthritis contains, as an active component, a sulfonate immunoglobulin (the interchain or inter and intrachain disulfide bond of immunoglobulin is cleaved to form a -S-SO3- group) prepared by purifing immunoglobulin existing in human blood by conventional method, and carrying out the S-sulfonation with sulfite ion in the presence of an oxidizing agent. In contrast with conventional remedy having insufficient effect because of side effects, the present remedy has remarkable effect and a high safety similar to the immunoglobulin preparation for intravenous injection used in the remedy of severe infection diseases, and is absolutely free from severe side effects. Dose of the active component; <=2,000mg/kg per dose, usually about 100-800mg/kg daily.

Description

[Detailed description of the invention] The present invention relates to a therapeutic agent for juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis <JRΔ) is a chronic rheumatoid arthritis that develops in children under 16 years of age, and is one of the most common incurable diseases among pediatric collagen diseases. The symptoms are diverse and affect the whole body, including arthritis (1iTl) and fever9.
Rash, quadrilateral contracture, morning stiffness, iritis.

Lymphadenoma clothes, Il! j Pain No. 2 Blood can be seen. The cause is either unknown or, since the clinical symptoms are considerably different from adult rheumatoid arthritis, the cause is likely to be different.

Treatment for juvenile rheumatoid arthritis includes therapeutic drug therapy,
Non-orthopedic surgery and physical therapy are used, but as the cause is unknown, there is still no definitive treatment. For drug treatment, nonsteroidal anti-inflammatory drugs such as salicylic acid, corticosteroid hormones, anti-inflammatory drugs such as gold preparations and D-penicillamine, and immunosuppressants are used, but there are problems with side effects. (The effect is not necessarily sufficient.

Recently, Sugisaki et al. reported that plasmin-treated gamma globulin was effective for adult ↑ and ν joint osteoarthritis (see Japanese Patent Application Laid-Open No. 58-21624), but the present inventors Based on the knowledge in the prior art, patients with juvenile rheumatoid arthritis can be treated with high-dose intravenous sulfonated immunoglobulin preparations that have few side effects and a very long half-life to restore natural immunoglobulin in vivo. When we tried this treatment method, we discovered that it was significantly effective in improving clinical symptoms, and thus arrived at the present invention.

That is, the present invention is a therapeutic agent for juvenile rheumatoid arthritis containing sulfonated immunoglobulin as an active ingredient.

The sulfonated immunoglobulin in the present invention refers to immunoglobulins present in human blood that can be prepared by alcohol precipitation,
After purification by known methods such as ammonium sulfate salting-out method, Affinitei chromatography, and polyethylene glycol treatment, it is purified in the presence of an oxidizing agent such as 1-thionate ion, trithionate ion, copper ion A, and oxygen. , S-sulfonated with sulfite ion (a -3-3O3- group is formed by cleavage of the disulfide bond in the immunoglobulin or the intrachain by micro-cleavage). A method for producing such a sulfonated immunoglobulin. is known from, for example, Japanese Patent Publication No. 17721/1982, Japanese Patent Publication No. 30331/1982, and Japanese Patent Application Laid-open No. 79023/1989.

The therapeutic agent for juvenile rheumatoid arthritis of the present invention can be obtained by adjusting sulfonated immunoglobulin together with known stabilizers, solubilizers, tonicity agents, etc. into an injection preparation by a known method. The specific composition of the formulation is, for example, as follows.

Composition Example 1 (in 100 m1i) Sulfonated immunoglobulin...s, 6 g Albumin......0.25"J
Glycine ・・・・・・・・・・・・・・・2.25
g Mannitol ・・・・・・・・・・・・・・・1.
0g Sodium chloride ・・・・・・・・・・・・・・・
0.9g Composition Example 2 <1oOmx) Sulfonated immunoglobulin...5.0g Glycine...2.5g Sodium chloride... ...0.89 The therapeutic agent for juvenile rheumatoid arthritis of the present invention is administered by intravenous injection.

Preferably, the composition is lyophilized and dissolved in distilled water for injection before use. Dosage is 2 times once
0001rKJ/89 or less, usually 100-800m! I
/Kg/day, and should be repeated several times while checking the patient's clinical symptoms.

The safety of the therapeutic agent of the present invention is essentially the same as that of intravenous immunoglobulin preparations used for the treatment of severe infections, and no serious side effects are observed.

Hereinafter, the excellent effects of the present invention will be explained in detail using Examples (clinical examples). The sulfonated immunoglobulin preparation used in the Examples was that of Composition Example 1, and only the active ingredient (IL) was shown in the Examples for convenience.

The example patient was a 12-year-old girl. The disease started when I was 3 years old, and I am currently at age 1.
He had eight episodes of fever that lasted for four weeks or more, and was hospitalized seven times. The immune complex in the blood was negative, and the rheumatoid factor (RF) was positive for 11, 116 and 116, and the disease was even more aggressive at the time of this recurrence. R' is a self-degenerated [G
It is an autoantibody and is thought to form a soluble immune complex combined with IgG in the blood.L, aspirin, and various anti-inflammatory drugs. ,
Treatment has been carried out with steroids, but sufficient clinical effects have not been obtained, and treatment has been difficult due to the side effects of the drugs.

Therefore, this time, we decided to use sulfonated immunoglobulin at 200mg/
Kgm was administered daily for 5 days, and the result was 39-40 kgm.
The fever, which had reached 0 °C, clearly subsided, and the rheumatoid factor, which was RA I-I A method <Wc+aler-Rose reaction>r640 times, decreased to less than 40 times, and the R△ test also changed from (廿) to (+ ) changed to The patient's general condition also improved markedly, and there was no recurrence even after 6 months of administration of sulfonated immunoglobulin, a remarkable effect that had not been seen with conventional drug therapy.

that's all Patent applicant Teijin Kaisha Ltd. Chemo and Serum Therapy Research Institute 2.t.′

Claims (1)

[Claims] 1. A therapeutic agent for juvenile rheumatoid arthritis containing sulfonated immunoglobulin as an active ingredient.