Immunosuppressive agent

Details Immunosuppressive agent Immunosuppressive agent

1987-07-30

1989-06-27

Robinson, Douglas W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514885, A61K 31335

Patent

active

048430927

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to an immunosuppressive agent containing an effective amount of one or more of the macrolide antibiotics of the formula (I): ##STR2## (wherein each of R.sub.1, R.sub.2, R.sub.3 and R.sub.4 is a methyl or ethyl group).


BACKGROUND ART

Macrolide antibiotics of the formula (I) according to the present invention are described in, for example, Helvetica Chemica Acta 38, 1445-1448 (1955), id. 45, 129-138 and 620-630 (1962), Journal of Antibiotics 23, 105-106 (1970), id. 24, 347-352 (1971), etc., and the process for preparing these antibiotics and their physicochemical properties are already known. Further, it is known that these compounds are effective in extermination of vermin such as acarids and cockroaches (see the specification of Japanese Patent Publication No. 46-28100), and it is also known that said macrolide antibiotics are useful as medicines for domestic animals and fowls, more specifically as growth promoting agents for animals (see the specification of Japanese Patent Public Disclosure No. 54-40178) and anti-coccidiosis agents (see the specification of Japanese Patent Public Disclosure No. 53-91143).
As immunosuppressive agents, there are known alkylating agents such as cyclophosamide, nucleic acid antimetabolites such as 6-mercaptopurine and azathiopurine, antibiotics such as mitomycin C, steroids, folic acid antagonists such as methotrexate, and plant alkaloids such as colchicine and vinblastine. These immunosuppressive agents are used as agents for suppressing rejection which may occur after transplantation of human organs or as medicines for treating patients suffering from autoimmune diseases. It has recently been noticed that cyclic polypeptides which are typified by cyclosporin A have immunosuppressive activity and noticeably suppress rejection occurring after organ transplantation. At the same time, vigorous studies have been made to achieve application of cyclic polypeptides to autoimmune diseases, and utility of these polypeptides has been confirmed.
The present inventors made exhaustive studies on the activity of compounds of formula (I) on the immune system which have a cyclic structure similar to that of cyclosporins and, as a result, they found the fact that compounds of the formula (I) have immunosuppressive activity. The present invention is based on this finding.


DISCLOSURE OF THE INVENTION

Compounds of the formula (I) are produced by cultivating Streotomyces aureus (FERM-P No. 233), and practical examples are the following five different kinds of compound listed in Table 1 below.


TABLE 1 ______________________________________ Compound No. 1 2 3 4 5 ______________________________________ R.sub.1 CH.sub.3 C.sub.2 H.sub.5 C.sub.2 H.sub.5 C.sub.2 H.sub.5 C.sub.2 H.sub.5 R.sub.2 CH.sub.3 CH.sub.3 C.sub.2 H.sub.5 C.sub.2 H.sub.5 C.sub.2 H.sub.5 R.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 C.sub.2 H.sub.5 C.sub.2 H.sub.5 R.sub.4 CH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 C.sub.2 H.sub.5 m.p. (.degree.C.) 148-149 63-64 73-74 79-80 105-106 ______________________________________
Macrolide antibiotics of the present invention which are obtained by fermentation are mixtures usually containing as principal components about 10% of Compound No. 3, about 40% of Compound No. 4 and about 50% of Compound No. 5, the mixtures being referred to as polynactin complex.
Compounds of the formula (I) are useful as immunosuppressive agents. More specifically, they are employed as agents for suppressing rejection that occurs after organ transplantation and as agents for treating autoimmune diseases. Examples of autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus (SLE), glomerulonephritis, autoimmune diseases in the ophthalmic region such as uveitis, and autoimmune diseases in the thyroid.


BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a graph showing the results of measurement of the anti-SRBC antibody production suppressing effects of selected compounds of the present invention by the PF

REFERENCES:
patent: 3743724 (1973-07-01), Kunio et al.
patent: 4136619 (1979-01-01), Sakamoto et al.
patent: 4166865 (1979-09-01), Sakamoto et al.
patent: 4205081 (1980-05-01), Sakamoto et al.
Journal of Antibiotics 23, 105-106 (1970), Oishi et al.
Jpn. Journal of Ophthalmol, 31 (2) 218-29 (1987), Tanouchi et al.
Immunology, 63(3), 471-5 (1988), Tanouchi et al.

Affiliated with

Also associated with

Rating

Immunosuppressive agent does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Immunosuppressive agent, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Immunosuppressive agent will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-814025