Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
2000-05-04
2000-12-26
Reamer, James H.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
A61K 31155
Patent
active
061660876
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The present invention concerns the use of 15-deoxyspergualin for the production of an immunosuppressive, anti-inflammatory and anti-tumoral pharmaceutical for administration to the mucous membrane in a dosage in the range from 20 to 600 .mu.m/kg body weight per day, especially for treating autoimmune illnesses, inflammatory skin disorders, cancer diseases and for the prevention of transplant rejection. The active substance (.+-.) 15-deoxyspergualin with the formula NH(CH.sub.2).sub.3 NH.sub.2 (3HCl)
The compound can be prepared either as a racemic mixture (cf, for example, U.S. Pat. No. 4,518,532) or else in optically pure form (cf., for example, EP-A-0 094 632).
Although numerous publications describe the immunosuppressive properties of this compound and its potential suitability for treating autoimmune illnesses, such as multiple sclerosis, lupus erythematosus and for preventing transplant rejection, its clinical benefit is very limited on account of the very high doses required and the associated side effects.
The main side effect observed in long-term therapy was a temporary drop in leucocyte count with all the consequences of a strong immunosuppression (cf. Amemiya, H,. et al.: Japanese [Journal] of Transplantation, 26, 615). The high dosages were regarded as necessary because of these demonstrable immunosuppressive effects in the therapy of acute and chronic rejection as well as in the treatment of autoimmune illnesses (cf. Amemiya., et al.: Transplantation Proceedings XXIII, (1), 1087-1089, February 1991).
Conventionally, 15-deoxyspergualin is administered intravenously in a dosage of approx. 4 to 6 .mu.g/kg of body weight to obtain an immunosuppressive effect. The effect is characterized by a non-specific general suppression of the immune system.
For treatment of autoimmune illnesses and cancer diseases and for the prevention of transplant rejection, at present no satisfactory long-term treatments with low side effects are available. The object of the invention is therefore to make available a preparation for the treatment of the aforementioned illnesses, which has low side effects, is easy to administer, does not develop significant side effects even during long-term use and is therapeutically effective. Furthermore, the preparation should be easy to administer even by the patient himself.
Surprisingly, it has now been found that extremely small dosages (20 to 600 micrograms/kg body mass) are sufficient to obtain the desired immunosuppressive pharmacological effects if the active substance is applied by way of the respiratory mucous membranes. The risk of undesired effects is considerably reduced, The ordeal of daily injection is eliminated. However, the low-dosage therapy presupposes that precise dosage systems are used in order to ensure the necessary constancy of dosage of highly effective immunosuppressants. In the dosage according to the invention, the active ingredient DSG can be administered by means of the preferred dosing aerosol precisely in the microgram range to the nasal mucous membrane, the respiratory tracts or other mucous membranes, the individual dosage being determined by the amount of active substance per stroke (200 to 800 microgram per stroke). Because of the low and, at the same time, precise dosage in the microgram range, it is possible for the first time to realize in practice the pharmacological effects that can be obtained in this dosage. In the process, both local and systemic effects are produced, since a sufficient amount of the active substance is resorbed and passes into the bloodstream. For long-term therapy, transdermal systems are also suitable in the low-dosage range.
The object of the invention is the use of 15-deoxyspergualin or a pharmaceutically compatible salt thereof as active substance, if appropriate with the conventional auxiliary and carrier substances and/or other active substances for the preparation of an immunosuppressive anti-inflammatory or anti-tumoral pharmaceutical in the form of a preparation intended for application to the mucou
REFERENCES:
Database WPI, Derwent Publications Ltd. AN 90-056185 & JP 02 011514.
Kintner Arent Fox
Reamer James H.
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