Chemistry of carbon compounds – Miscellaneous organic carbon compounds – C-metal
Patent
1981-06-04
1984-05-15
Bleutge, John C.
Chemistry of carbon compounds
Miscellaneous organic carbon compounds
C-metal
435 68, 435884, 424177, C07G 700
Patent
active
044487142
DESCRIPTION:
BRIEF SUMMARY
This invention relates to antibiotic substances, a process for the preparation and compositions thereof and methods of treatment therewith. The invention further relates to a new strain of Staphylococcus epidermidis which produces the antibiotic substances, compositions, containing the said strain and a method of cosmetic or prophylactic treatment of the human skin with such composition. The antibiotic substances having a bactericidal action against Gram-positive bacteria.
Staphylococci are known to produce at least three classes of substances having an inhibitory action on the growth of bacteria, namely bacteriocins, bacteriolytic enzymes and low molecular weight antibiotics. Publications describing the production of low molecular weight antibiotics from staphylococci are as follows: 212-216. Symposium on staphylococci and staphylococcal infections, p 599-621. Edited by J. Jeljaszewicz. Stuttgart: Fischer-Verlag. the 9th International Congress of Chemotherapy, 5 (1975), p 391-396. Edited by J. D. Williams and A. M. Geddes. New York. SWICK, L. and SONN, C., J. Immunol., 70 (1953) p 400-410. above-mentioned publications has however been demonstrated to exhibit a bactericidal action resulting in lysis of the bacterial cells.
In J. Med. Microbiol, 12 (1979), p71-82, experiments are described in which numerous strains of resident human skin bacteria comprising 93 isolates of Propionobacterium acnes and 148 isolates of Micrococcaceae were screened for their ability to inhibit the growth of various indicator strains of P. acnes and Staphylococcus epidermidis. Fifty-three strains out of those tested showed some activity against at least one indicator strain, and both broad- and narrow- spectrum inhibition was detected. The strains which were examined were derived from 36 acne patients and 8 control subjects, and the main purpose of the investigations was to find whether the possession of inhibiting strains and conversely the possession of sensitive strains in patients results in a predisposition to acne. The particular strains of P. acnes and Micrococcaceae which were screened are not identified except by means of an internal reference. Moreover there is no description of any attempt to recover the active substances responsible for the inhibition which was observed.
The present invention is based upon the discovery that a particular strain of Staphylococcus epidermidis, i.e. Staphylococcus epidermidis NCIB 11536 (which was deposited in the National Collection of Industrial Bacteria, Torrey Research Station, P.O. Box 31, 135 Abbey Road, Aberdeen AB9 8DG 3rd October, 1979), or a mutant strain thereof, can be cultured to produce a new low molecular weight antibiotic polypeptide which exhibits broad spectrum activity against Gram-positive bacteria and which is distinguished from the low molecular weight antibiotics hitherto produced by staphylococci by the fact that it possesses a bactericidal action resulting in lysis of the bacterial cells.
According to one aspect of the present invention we therefore provide an antibiotic polypeptide compound, or addition salt thereof, having a molecular weight no greater than 10000 and possessing bactericidal and bacteriolytic activities in respect of Gram-positive bacteria, the said compound comprising within the molecular structure thereof amino acid derivative units of formulae ##STR3## wherein NH.sub.2 --R.sub.1 --COOH, NH.sub.2 --R.sub.2 --COOH, NH.sub.2 --R.sub.3 --COOH, NH.sub.2 --R.sub.4 --COOH, NH.sub.2 --R.sub.5 --COOH, NH.sub.2 --R.sub.6 --COOH and NH.sub.2 --R.sub.7 --COOH respectively represent isoleucine, phenylalanine, alanine, aspartic acid, glutamic acid, lysine and glycine and ##STR4## represents proline. The compound has UV absorption maxima at about 210 nm and at from about 260 to 280 nm.
Particularly suitable amongst the antibiotic polypeptides of the present invention is an antibiotic molecular weight of about 950 and comprising within the molecular structure thereof an amino acid derivative unit of each of the following formulae ##STR5## and a further amino
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patent: 3278378 (1966-10-01), Schindler
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Cunliffe William J.
Eady Elizabeth A.
Holland Keith T.
Bleutge John C.
Short Patricia
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