PGE1 and derivatives for dermal or mucosal application

Abstract: Disclosed is the use of Prostaglandin E₁, its derivatives and analogs and the physiologically com­ patible esters, amides, phospholipids and glycolipids thereof in a pharmacologically effective dosage form for the topical or inhalative treatment of acute manifest atopy in the dermal and mucosal areas. The substances used according to the invention are preferably used in combination with gamma-linolenic acid, 15-hydroxy-­ dihomo-gamma-linolenic acid and dihomo-gamma-linolenic acid, the physiologically compatible salts, esters, amides, phospholipids and glycolipids thereof.

Description: The invention relates to the new use of Prostaglandin E 1 , Prostaglandin E 1 derivatives and Prostaglandin E 1 analogs, the physiologically compatible salts, esters, amides, phospholipids and glycolipids thereof for the topical and inhalative treatments of acute manifest atopies in the dermal and mucosal areas and a combination with another active substance. The Japanese Laid-Open Patent Application [JP-OS] 88/145230 (63/145230) relates to the use of Prostaglandin E 1 as a therapeutic and prophylactic pharmaceutic for the treatment of certain brain diseases. Furthermore, it has been known from the JP-OS 87/223120 (62/223120) that AIDS may possibly be controlled by a combination treatment with various prostaglandins. According to the EP-A-257 859, a combination tissue plasminogen activator-prostaglandin can be used as a thrombolytic agent. The EP-A-100 630 relates to analogs of Prostaglandin E 1 which can be employed for protection against cytotoxic substances, above all in the liver. From the German Laid-Open Patent Application DE-OS 33 15 356 it has been known that Prostaglandin E 1 derivatives and their cyclodextrin inclusion complexes as well as their salts can be employed, when administered orally or parenterally, against brain ischemia. Various other literature references relate to the synthesis and use of PGE 1 derivatives and analogs. So, US-A-4,009,282 teaches the treatment of proliferating skin diseases with prostaglandins. There is, however, no drug on the market with PGE 1 . So far, however, for the treatment of atopy there have been generally used substances such as antihistamines, glucocorticoids and beta-sympatheticomimetic agents. Nevertheless, in practice since long there has been a great need for fast-acting substances which, especially in the case of an acute manifest atopy in the dermal and mucosal regions will provide an immediate relief. M. Schalin-Karrila (in Br. J. Dermatol. 117 (1), 1987, 11-20) reported in DIALOG BIOSIS Previews File 5 (Title: Evening primrose oil in the treatment of atopic eczema effect on clinical status plasma phospholipid fatty acids and circulating blood prostaglandins) that primrose oil is active against atopic eczema. EP-A-0,381,823 teaches a combination of cytotropic heterogenous molecular lipids (CHML) and a process for preparing the same. This can include prostaglandins, however, only Prostaglandin E 2 and not Prostaglandin E 1 . The combination of CHML can injure carcinoma cells and various virus. It can enhance the immunity of the body. There is, however, no indication about an activity as topical or inhalative treatment of acute manifest atopies in the dermal and mucosal areas. It is the object of the present invention to provide an immediately effective agent in cases of acute manifest atopies in the dermal and mucosal areas. Said object can been attained by a surprisingly simple route by using one or more substances selected from, PGE 1 , PGE 1 derivatives and PGE 1 analogs, their physiologically compatible salts, esters, amides, phospholipids and glycolipids and, in addition, one or more substances selected from gamma-linolenic acid, 15-hydroxy-dihomo-gammalinolenic acid and dihomo-gamma-linolenic acid, the physiologically compatible salts, esters, amides, phospholipids and glycolipids thereof for the manufacture of a medicament for the topical or inhalative treatment of acute manifest atopy in the dermal and mucosal areas. A further object is a combination of one or more substances selected from PGE 1 , PGE 1 derivatives and PGE 1 analogs, their physiologically compatible salts, esters, amides, phospholipids and glycolipids and, in addition, one or more substances selected from gamma-linolenic acid, 15-hydroxy-dihomo-gammalinolenic acid and dihomo-gamma-linolenic acid, the physiologically compatible salts, esters, amides, phospholipids and glycolipids thereof for the topical or inhalative treatment of acute manifest atopy in the dermal and mucosal areas. The combination according to the invention can be used for the topical or inhalative application in the form of eye drops, nose sprays, creams, lotions or also in the form of aerosols. Gamma-linolenic acid is present, inter alia , in the oil of the black evening primrose (Oenothera biennis) and in the seeds of black currants. In addition, there is a number of other natural sources of gamma-linolenic acids (e.g. Borago officinalis) . Dihomo-gamma-linolenic acid is obtainable, inter alia , by the process according to the EP-A-252 716 from Mortierella cultures. Now, the advantage of the present invention above all is to be seen in that by virtue of the Prostaglandin E 1 therapy there is immediate relief from the atopic symptoms. Furthermore, the use of the substances according to the invention in combination with gamma-linolenic acid and/or dihomo-gamma-linolenic acids and/or the pharmacologically reasonable dosage forms thereof contributes to some prevention, since these substances, as a rule, are only slowly metabolized to form PGE 1 .

Claims: Use of one or more substances selected from PGE 1 , PGE 1 derivatives and PGE 1 analogs, their physiologically compatible salts, esters, amides, phospholipids and glycolipids and, in addition, one or more substances selected from gamma-linolenic acid, 15-hydroxy-dihomo-gammalinolenic acid and dihomo-gamma-linolenic acid, the physiologically compatible salts, esters, amides, phospholipids and glycolipids thereof for the manufacture of a medicament for the topical or inhalative treatment of acute manifest atopy in the dermal and mucosal areas. A combination of one or more substances selected from PGE 1 , PGE 1 derivatives and PGE 1 analogs, their physiologically compatible salts, esters, amides, phospholipids and glycolipids and, in addition, one or more substances selected from gamma-linolenic acid, 15-hydroxy-dihomo-gammalinolenic acid and dihomo-gamma-linolenic acid, the physiologically compatible salts, esters, amides, phospholipids and glycolipids thereof for the topical or inhalative treatment of acute manifest atopy in the dermal and mucosal areas.

Inventors: MELNIK B DR MED, PLEWIG G PROF DR MED, MELNIK, B., DR. MED., PLEWIG, G., PROF. DR. MED.
Applicants: BEIERSDORF AG, BEIERSDORF AKTIENGESELLSCHAFT
Application year: 1990
Main classification: A61K31
IPC codes: A23L1, A61K31