Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated via claimed linking group – bond – chelating agent,...
Patent
1981-12-23
1984-08-07
Brown, Johnnie R.
Drug, bio-affecting and body treating compositions
Conjugate or complex of monoclonal or polyclonal antibody,...
Conjugated via claimed linking group, bond, chelating agent,...
536 53, 536 551, A61K 3173
Patent
active
044643608
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
The present invention relates to compounds for use in medicine, and novel pharmaceutical preparations containing as active ingredient these compounds which are known per se. The pharmaceutical preparations are especially useful for inhibiting the adherence of bacteria to human urinary tract epithelial cells, and can be used for treatment, prophylaxis and diagnosis of urinary tract infections.
2. Background Art
Bacteria tend to grow attached to surfaces. Besides the general "stickiness" enabling bacteria to bind to almost any surface, host and tissue specific attachment of bacteria is known. Such specific attachment guides the distribution on mucous membranes, both of bacteria constituting the indigenous flora and of potential pathogens and is believed to be a prerequisite for susceptibility to infection of the host. For Escherichia coli isolated from patiens with urinary tract infection the severity of infection produced in vivo is strongly related to the capacity to adhere to human urinary tract epithelial cells in vitro.
The carbohydrate chains of glycosphingolipids are extremely variable, and are known to be involved in self- not self recognition as blood group antigens and receptors for bacterial toxins. Furthermore, the glycolipid pattern is species specific and differs between epithelial and non epithelial tissue. Carbohydrates at the cell surface have been implicated as possible receptors for attaching bacteria but no epithelial cell component interacting with bacteria has been identified. In connection with a recent observation (Svanborg Eden C, Leffler H. Scand. J. Infect. Dis. 1980, Suppl 24:144-147) that a fraction of glycolipids, isolated from human urinary tract epithelial cells, inhibited attachment of E. coli to cells from the same donor, a role for glycolipids as receptors for the attaching bacteria was suggested but no specific glycolipid had been identified before the date of our invention.
DISCLOSURE OF INVENTION
According to the present invention it has been found that the compounds globotetraosylceramide, globotriaosylceramide, and globotetraos have the ability to inhibit the adherence of bacteria to human urinary tract epithelial cells. Biological tests have indicated that this unexpected action is due to the fact that these compounds have the ability to attach to the cell walls of bacteria and thereby block some ligand function which is responsible for the adherence of bacteria to human urinary tract epithelial cells.
Urinary tract infections are commonly caused by an invasion of pathogenic bacteria, either from bacteria in the bowels or by bacteria invading through the urethra opening. The present invention provides pharmaceutical compositions having the ability to prevent adherence of potential pathogenic bacteria to human urinary tract epithelial cells, and thereby curing or preventing urinary tract infections.
More specifically, the invention relates to pharmaceutical preparations for inhibiting bacterial adherence to human urinary tract epithelial cells, which contain as active ingredient an effective amount of at least one of the compounds globotetraosylceramide of the formula arw.1CERAMIDE (I)
In a preferred embodiment the invention also relates to pharmaceutical preparations which contains solely globotetraosylceramide and/or globotriaosylceramide as an active ingredient. These preparations may as an additional ingredient contain an effective amount of the compound lactosylceramide of the formula. I and II. Lactosylceramide does not in itself possess any ability to inhibit bacterial adherence. However, most surprisingly it has been found to strongly potentiate the inhibitory effects of globotetraosylceramide and globotriaoxylceramide.
The active ingredients globotetraosylceramide, globotriaosylceramide, globotetraos and lactosylceramide are compounds known per se, which can be prepared according to known methods. These compounds have not previously been suggested to possess any medical use.
The active ingredients may according to the inventi
REFERENCES:
patent: 4125492 (1978-11-01), Cautrecasas
patent: 4182757 (1980-01-01), Tsujihara et al.
patent: 4238473 (1980-12-01), Lemieux et al.
Chemical Abstracts, vol. 84, 1976, abstract No. 15602f, Biochemistry, 1975, 14, (22), 4837-41.
FEMS Microbiology Letters, vol. 5, 1979, G. Kallenius, R. Mollby, "Adhesion of Escherichia coli to Human Periurethral Cells Correlated to Mannose-Resistant Agglutination of Human Erythrocytes", pp. 295-299.
Glycoconjugate Research, Proceedings of the 4th International Symposium on Glycoconjugates, vol. 1, 1979, Ed. by J. D. Gregory and R. W. Jeanloz, (Academic Press, N.Y.-San Francisco-London), pp. 480-491.
Methods in Membrane Biology, vol. 2, 1974, Ed. by E. D. Korn, Plenum Press, N.Y.-London, P. A. Laine et al., "Isolation and Characterization of Membrane Glycosphinogolipids", pp. 205-244.
Chemical Abstracts, vol. 93, No. 17, issued 1980, Oct. 27, abstract No. 165835j, FEMS Microbiol. Letter, 1980, 8, (3), 127-34.
Euro. J. of Biochem., vol. 104, No. 2, issued 1980, Mar., Springer-Verlag, Berlin-Heidelberg-N.Y., A. Lundblad et al., "Release of Oligosaccharides from Human Erythrocyte Membranes of Different Blood-Group-P Phenotypes by Trifluoroacetolysis", pp. 323-330.
Proceedings of the National Academy of Sciences USA, vol. 73, No. 9, Sep. 1976, Washington, D. M. Marcus et al., "Abnormalities in the Glycosphingolipid Content of Human P.sup.k and p Erythrocytes", pp. 3263-3267.
Chemical Abstracts, vol. 52, 1958, 18581 a, Seitai no Kagaku, 6, 1955, 204-217.
Chemical Abstracts, vol. 85, 1976, abstract No. 92009r, J. Biochem., (Tokyo), 1976, 79, (6), 1253-61.
Chemical Abstracts, vol. 88, 1978, abstract No. 166344g, Proc. Natl. Acad. Sci. USA, 1978, 75, (2), 941-5.
Pathologie Biologie, vol. 26, No. 2, 1978, J. Delaunay, "Les Constituants De La Membrane Erythrocytaire", pp. 117-136, especially pp. 127-131.
Eden Catharina Svanborg
Leffler Hakon
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