Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1990-06-22
1993-04-06
Cashion, Jr., Merrell C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 11, 514 17, 514 16, 514375, 530317, 530329, 530330, A61K 3700, A61K 3702, C07K 702, C07K 500
Patent
active
052003949
DESCRIPTION:
BRIEF SUMMARY
OBJECT OF THE INVENTION
The present invention concerns derivatives of synergimycin, more specifically virginiamycin S and derivatives of virginiamycin M. It also relates to a process for the preparation of these derivatives. Further, their uses in human and veterinary medicine, and for the production of antibodies against the above antibiotics are also described.
OUTLINE OF TECHNICAL BACKGROUND
Virginiamycins S and M belong to a family of antibiotics generally known under designations such as "synergistins", "synergimycins" and "streptogramins". These antibiotics, as produced by streptomycetes, are mixtures of two types of compounds, A and B, which in vivo display a synergistic activity. Type A compounds from different microorganisms are similar as well as the type B compounds. However, the structures of A and B compounds are different.
Numerous work on these antibiotics have been published and several products are available under different commercial names (cf. the Merck Index, 10th ed., 1983, Merck & Co, Inc., Rahway, N.J., US, pag. 1432, Nx9810 "Virginiamycin").
Techniques for production of antigenic modification of polypeptides capable of inducing the formation of antibodies are also known (cf., e.g., EP, A, 0117934, The Ohio State University, Sep. 12, 1984, pag. 1-7).
DISADVANTAGES OF THE KNOWN PRODUCTS
In spite of the fact that an A+B mixture is more powerful than most antibiotics, the medical use of synergimycins has been limited by their poor water solubility. In fact, the level of absorbtion as from the intestin is very low and the blood-to-tissue partition coefficient is unfavorable.
AIMS OF THE PRESENT INVENTION
The aim of the present invention is to provide derivatives of natural products of the type A and B synergimycins, and more specifically of virginiamycins M and S.
An other aim of the present invention is to provide derivatives of the above mentioned type having a modified solubility in aqueous media, thus allowing the attainment of higher concentrations in blood and tissues.
A complementary aim consists in providing derivatives of virginiamycin and more particularly virginiamycin S and M showing a high therapeutic activity in the case of microbic diseases, resulting from their intrinsic properties.
According to another aspect, the present invention provides a process for the preparation of said derivatives as from natural products, which are produced by appropriate streptomycetes.
According to a complementary aspect of the present invention concerns uses of said antibiotics in human and veterinary medicine and for the production of antibodies directed against virginiamycins.
DESCRIPTION OF THE PRINCIPLES OF THE INVENTION
The derivatives of synergimycin which are dealt with by the present invention are those selected from the group consisting of compounds of general formula Z--X--R where Z is a synergimycin radical of type A or B which is linked through its reactive carbonyl and by means of an arm of the type .dbd.N-- or .dbd.N--O-- to a substituent R representing a hydrogen atom, an alkyl group, an alkyl-COOH group, an alkyl (.alpha.--NH.sub.2)COOH group, an ##STR1## group, an ##STR2## group, an (-alkyl-CO--NH).sub.n protein group or an (-alkyl-CONH).sub.n ribosome group where n is a function of the NH.sub.2 content of the coupling protein as well as pharmaceutically acceptable salts, esters and, optimaly, acid addition compounds with pharmaceutically acceptable acids.
The invention concerns more particularly derivatives of synergimycin of the above defined type wherein Z represents the virginiamycin M radical of formula ##STR3## and the virginiamycin S radical of formula ##STR4## X and R being as already defined.
It has been noted that the derivatives of the invention are biologically active and have a water/organic solvents partition coefficient more favorable than those of the starting products.
According to the present invention derivatives of the type Z.dbd.N--O--R, which are endowed with higher stability in aqueous media are preferred.
It should further be noted that t
REFERENCES:
The Merck Index, ed. 10, 1983, p. 1432 Abst. No. 9810 "Virginiamycin".
Cocito Carlo
Di Giambattista Mario
Pecher Andre
Cashion Jr. Merrell C.
Davenport A. M.
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