SK111894A3 - Pharmaceutical agents for treatment of granulomatese and fibrously pulmonary illnesess - Google Patents

Abstract

Use of pentoxyfylline (I) for treating granulomatous and fibrotic lung diseases is new.

Description

Technical field

The invention relates to the use of pentoxifylline for the treatment of granulomatous and fibrotic pulmonary diseases.

BACKGROUND OF THE INVENTION

Pulmonary granulomatosis is a disease-related multiplication of connective tissue in the pulmonary meshwork, which results from various harmful effects on the lungs. The harmful substances that cause the development of granulomatous lung disease are mycobacteria, immunocomplexes, antibodies as well as many other substances. In contrast, in sarcoidosis, the stimulus is immense. Sarcoidosis is a systemic granulomatous disease of unknown etiology, which usually results in granulomatous changes in the lungs and hilic lymph nodes. Optionally, all organs, especially the CNS, liver, heart, eyes and bones, can be involved in the systemic disease process. Pulinonal changes may turn into irreversible pulmonary fibrosis with permanent organ damage in chronic process activity.

The means of choice is the symptomatic, systemic corticosteroid therapy for the treatment of said pulmonary diseases of the prior art. As it is a long-term corticosteroid therapy with doses above the Cushing threshold, the usual corticosteroid-induced side effects may occur. In the case of fibrotic lung diseases, corticosteroid therapy, either alone or in combination with other immunosuppressants and cytostatics, is recommended by the prior art according to the prior art. Overall, however, it can be stated that a higher percentage of pulmonary fibrosis does not respond to any of these therapeutic forms, as long-term treatment with these substances and corresponding drastic side effects is required. Pulmonary fibrosis, resulting from systemic scleroderma, does not respond regularly to any of the therapies known so far, so that scleroderma-mediated lung fibrosis leads to death.

SUMMARY OF THE INVENTION

It has been found that pentoxifylline is suitable for the treatment of these diseases without the side effects associated with the hitherto known treatments.

In an open-label therapeutic study, it was found that in patients with bronchoscopically proven intratoracal sarcoidosis, these respond in 80% of cases to corresponding pentoxifylline treatment of 4 to 5 x 400 mg per os / day after 3 to 6 months. It has been shown that the radiological changes in the lungs and hilic lymph nodes are diminishing, or the lung function parameters are improved or normalized. In about 30% of cases, after the end of the pentoxifylline therapy, the disease activity was restored after 6 months and stopped again after the pentoxifylline therapy was resumed. Unfortunately, in 16% of the cases it was found that there was no response to pentoxifylline and only a combination of therapies consisting of pentoxifylline and corticosteroids could achieve radiological improvement and improved lung function with sustained remission.

The dose of pentoxifylline used naturally depends on the severity of the disease, the condition and the weight of the patients treated. However, it is generally from 1.00 to 3.00 g / day and preferably from 1.20 to 2.50 g / day.

As already mentioned, pentoxxphylline can be used in combination with corticosteroidini. Preferred corticosteroids are prednisone, prednisolone, prednisolone-21-acetate, prednylidene and methylprednisone. The concentration of corticosteroids used is in. Initial phase (about 2 weeks) 0.3 to 1.2 mg, preferably 0.5 to 1.0 mg / kg body weight. The initial phase is followed by a slow dose reduction to a maintenance dose of 2.5 to 7.5 mg / day, preferably 10 to 20 mg / day.

The preferred application of the formulations is per os, but other forms of administration are also possible.

DETAILED DESCRIPTION OF THE INVENTION

Example 1 • A male patient (51 years, 88 kg, WL) who has been known for 7 years with progressive systemic scleroderma (Raynaud's phenomenon on acres with toes and toes, swallowing disorders in the esophagus, lung fibrosis with highly graded respiratory tract has been treated without effect according to various immunosuppressive therapeutic regimens (high doses of corticosteroids with cyclophosphamide, plasma separation with cyclophosphamide shock therapy, corticosteroids with cyclosporin A). After 3 months of treatment with the combination of pentoxifylline (5 x 400 mg orally / day) with corticosteroids at a decreasing dose up to maintenance therapy of 10 mg methylprednisolone orally / day, a significant radiological finding of fibrosis change regression, normalization of blood gas at rest and disappearance of disorders necrosis in acres. To date, remission has been maintained for more than 1 year while continuing the therapy.

Example 2

A male patient (45 years, 61 kg, R.S.), who has been diagnosed for 6 years with progressive scleroderma (esophageal swallowing disorders, lung fibrosis with respiratory global insufficiency), long-term oxygen therapy, did not respond to a variety of immunosuppressive strategies. Combination of pentoxifylline (4 x 400 mg orally / day) with corticosteroids at decreasing doses up to 20 mg methylprednisolone orally / day resulted in an excellent improvement in lung function parameters (respiratory partial insufficiency) after 6 months of therapy.

Examples of 3 to 7 patients (female 28 years, CW; female 45 years, DH; male, 48 years, KK; male 24 years, GH; male 42 years, JS) show a therapeutic response documented by decreasing lung radiological changes and helix nodes and / or by improving or normalizing the lung function parameter. Pancients received only pentoxifylline at a dose of 4 x 400 mg orally / day.

Example 8

The patient (male, 31 years, H.G.) did not respond to pentoxifylline by any response to disease activity change, so the therapy was changed to corticosteroid therapy. Also, when there was no effect after 6 weeks, he was treated with a combination of pentoxifylline with corticosteroids (4 x 400 mg oral / day and 60 mg methylprednysolone oral / day). After two weeks there was an improvement, documented radiologically, in lung function, thus the corticosteroid dose could be reduced to a maintenance dose of 10 mg / day. Remission persists after 9 months.

Examples 9 to 10

In 2 patients (female, 28 years, GW; female, 45 years, DH) ^1, after the end of pentoxifylline therapy, the disease activity resumed after 6 months, which resumed upon reintroduction of pentoxifylline 4 x 400 mg / day. In addition, both patients received 10 mg of prednisone / day administered orally.

Claims (3)

PATENT CLAIMS Use of pentoxifylline for the manufacture of pharmaceutical compositions for the treatment of granulomatous and fibrotizing pulmonary diseases. Use according to claim 1 in combination with one or more other therapeutically active substances. Use according to claim 2, characterized in that the further active ingredient is a corticosteroid from the group of non-fluorinated glucocorticoids.