specific examples of alkyl residues are the methyl , ethyl , n - propyl , isopropyl , n - butyl , isobutyl and tertiary butyl group . due to the non - toxicity of the fragments , the preferred group r 2 is the ethyl group . the preparation of the compounds of general formula i is carried out according to methods known per se via esterification of pge1 and 6 - k pge1 . the methyl and ethyl ester , for instance , are prepared by reacting the same with diazomethane or diazoethane ; also see ch . j . sih et al ., j . am . chem . soc ., vol . 97 ( 1975 ), pp . 857 to 865 . the compounds of general formula i can be used to treat circulatory insufficiencies , for instance of the brain , the heart and the extremities , to inhibit platelet aggregation ( thrombocyte aggregation ), impotence and to treat allergic reactions such as bronchial asthma , rejection following transplantations and impaired hair growth . typical examples of deficiencies in the cerebral blood supply are transitory cerebral ischaemia acute loss of hearing , vertigo caused by circulatory insufficiencies and ischaemic strokes . typical examples of deficiencies in the myocardial blood supply are angina pectoris and myocardial infarction . typical examples of deficiencies in the blood supply of the extremities are periphal arterial circulatory insufficiencies in arteriosclerosis and raynaud &# 39 ; s disease and raynaud &# 39 ; s syndrom . the compounds of general formula i can also be used to treat gastrointestinal ulcers and ulcers of the skin . typical examples of gastrointestinal ulcers are ulcus ventriculi , duodenal ulcers and ulcerative colitis ( crohn &# 39 ; s disease ). a typical example of a skin ulcer is ulcus cruris . the compounds of general formula i have a cyto - protective effect . the cells exhibit increased resistance to noxious stimuli . the compounds of general formula i can further be used to treat haematomas , especially surface haematomas . in addition to transcutaneous transdermal administration , the compounds of general formula i can also be administered by inhalation , intravenously and intra - arterially and in each case incorporated into microsomes . the preparation of pharmaceutical compositions is carried out according to conventional methods . for the preparation of pharmaceutical compositions to be administered transcutaneously , the compounds of general formula i can be mixed with a gel , ointment or liquid vehicle either with or without various solvents and stabilizers . the packages used are sprays , tubes , ampules and individual doses . once applied to the skin either with or without an additional occlusive dressing , the active agent is absorbed . the compounds of general formula i can also be placed either with or without stabilizers and solvents onto a plaster and can then be applied as such . the conversion of the ethyl ester to pge1 in the human body was demonstrated in the following way : an isotopically labelled pge1 ethyl ester was applied in the manner described above . the isotopically labelled urinary metabolites were separated with hplc and compared with the retention time of the main metabolite of pge1 ( 7α - hydroxy - 5 , 11 - diketotetranorprosta - 1 , 20 - dioic acid ). it was found that after administration of the pge1 ethyl ester , the main metabolite was identical to the main metabolite after administration of pge1 . this proves that the pge1 ethyl ester is a pro - drug of pge1 . excess diazoethane in diethyl ether ( 17 mg / ml ; 0 . 3 mmol ) is added to 500 μg pge1 ( 1 . 31 μmol ) in 500 μl ethanol under stirring and cooling . the reaction mixture is taken out of the cooler and is stirred until it reaches room temperature . stirring is then continued for a further 30 minutes . the excess diazoethane and the ethanol are removed at room temperature by a stream of nitrogen . the product is purified by high - pressure liquid chromatography ( rp 18 ). in the same manner and with excess diazoethane , 500 μg of 6 - keto pge1 in 500 μl of ethanol are reacted and processed in diethyl ether . the ester is purified by high - pressure liquid chromatography ( rp 18 ). 250 μg of prostaglandin e1 ethyl ester together with an isotopically labelled pge1 - ethyl - ester in 250 μl of ethanol were worked into 2 g of a gel vehicle of the composition as indicated below . the gel was applied to the upper arm and rubbed in for 1 minute . the application area was covered with a plastic foil . one week later , 250 μg of prostaglandin e1 together with an isotopically labelled pge1 in 250 μl of ethanol were mixed with 2 g of a gel vehicle of the composition as indicated below . it , too , was applied to the upper arm and rubbed in for 1 minute . measurement of the absorbed quantity was carried out by determining the isotopically labelled prostaglandin metabolites in the urine . for this , the total urine was collected in portions from the beginning of the application onwards . four hours after the application , the plastic film was removed and the excess gel wiped off . as can be seen in fig1 the absorption rate of pge1 ethyl ester ( 23 %) was clearly better than that of pge1 ( approx . 4 %). ______________________________________isopropanol 40 . 0 gdiisopropyl adipate 0 . 5 gcarbopol 940 2 . 0 gtrometamol 1 . 91 gpurified water ad 100 . 0 g______________________________________ the water , alcohol and diisopropyl adipate are mixed , the carbopol is dispersed in this mixture and left to swell . the gel is neutralized with the aqueous trometamol - solution .
the invention describes prostaglandin e1 derivatives as pharmacologically active agents , and pharmaceutical compositions containing these compounds , especially for transcutaneous administration .