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Lys-pro-val dimer, formulations and applications

Inactive Publication Date: 2003-09-18
CATANIA ANNA P +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0028] In addition to its anti-inflammatory and anti-pyretic function, one aspect of the present invention involves the anti-microbial or anti-infection activity of .alpha.-MSH and / or its derivatives. As described below, .alpha.-MSH and / or its derivatives have significant anti-infection uses, including, for example, use in reducing the viability of microbes, reducing the germination of yeast, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation associated with microbial infection without reducing microbial killing, increasing the accumulation of cAMP in microbes, and inhibiting the replication and expression of viral pathogens.

Problems solved by technology

They are normally non-pathogenic, but when a change in their environment occurs, such as in response to a woman's hormonal changes in menopause, pregnancy, or in response to stress, they can overgrow to cause a yeast infection.
Although it is very effective, some strains of S. aureus have developed resistance to methicillin, and only a few antibiotics can successfully treat these methicillin-resistant Staphylococcus aureus (MRSA).
Ultimately, it can even ascend to the kidneys through the ureters and cause pyelonephritis.

Method used

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  • Lys-pro-val dimer, formulations and applications
  • Lys-pro-val dimer, formulations and applications
  • Lys-pro-val dimer, formulations and applications

Examples

Experimental program
Comparison scheme
Effect test

example ii

[0043] This example illustrates the anti-fungal properties of .alpha.-MSH and / or its derivatives against Candida albicans.

[0044] Clinical isolates of C. albicans were also obtained from the collection of the Department of Microbiology, Ospedale Maggiore di Milano. Cultures of C. albicans were maintained on Sabouraud's agar slants and periodically transferred to Sabouraud's agar plates and incubated for 48 hours at 28.degree. C. To prepare stationary growth-phase yeast, a colony was taken from the agar plate, transferred into 30 ml of Sabouraud-dextrose broth, and incubated for 72 hours at 32.degree. C. Cells were centrifuged at 1000.times.g for ten minutes, and the pellet was washed twice with distilled water. Cells were counted and suspended in Hank's balanced salt solution ("HBSS") to the desired concentration. Viability, determined by exclusion of 0.01% methylene blue, remained greater than 98%.

[0045] At 1.times.10.sup.6 / ml in HBSS, these fungi were incubated in the presence or a...

example iii

[0047] This example compares the anti-infection activities of .alpha.-MSH and / or its derivatives to fluconazole, an established anti-fungal agent.

[0048] .alpha.-MSH (1-13) (SEQ. ID. NO.4), (4-10) (SEQ. ID. NO.2), (6-13) (SEQ. ID. NO.3), (11-13) (SEQ. ID. NO. 1), ACTH (1-39), (18-39), and fluconazole, at concentrations of 10.sup.-6 to 10.sup.-4 M, were tested against C. albicans using the same procedures as in Example II. FIG. 4 shows that compared with fluconazole, .alpha.-MSH (11-13) (SEQ. ID. NO. 1), (6-13) (SEQ. ID. NO. 3), and (1-13) (SEQ. ID. NO. 4) were most effective against C. albicans. Their inhibitory activities were similar to fluconazole at the same molar concentration. In contrast, the "core" .alpha.-MSH sequence (4-10) (SEQ. ID. NO. 2), which has behavioral effects but little anti-inflammatory activity, caused approximately 50% inhibition of colony forming units (CFU). Although this inhibitory effect was substantial (p<0.01 vs. control), it was significantly less poten...

example iv

[0050] This example illustrates that .alpha.-MSH and its derivatives inhibit the germination or germ tube formation of C. albicans. Germ tube formation is a significant part of the pathogenesis of C. albicans infection. This pathogenesis involves adhesion to host epithelial and endothelial cells and morphologic switching from the ellipsoid blastospore to various filamentous forms, e.g. germ tubes, pseudohyphae, and hyphae. Gow, N. A., Germ Tube Growth of Candida albicans, Curr. Topics Med. Myco. 8, 43-55 (1997).

[0051] C. albicans from stationary phase cultures were washed twice with distilled water and suspended in HBSS to a final concentration of 2.times.10.sup.6 / ml. Hyphal growth was induced by addition of 10% inactivated horse serum (GIBCO / BRL, Paisley, Great Britain) to yeast incubated for 45 minutes at 37.degree. C. with continuous shaking. Horse serum was then removed by washing cells twice with HBSS, and incubation was further continued for 60 minutes at 37.degree. C. in the...

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Abstract

The present invention is directed to a system for treating uro-genital conditions. One aspect of this invention involves the treatment system comprising one or more polypeptides with a amino acid sequence including KPV (SEQ. ID. NO. 1), MEHFRWG (SEQ. ID. NO. 2) HFRWGKPV (SEQ. ID. NO. 3), SYSMEHFRWGKPV (SEQ. ID. NO. 4), for treatment of uro-genital conditions. The one or more polypeptides can also be a dimer formed from any of the amino acid sequence above. Uro-genital conditions can include infections, inflammation, or both. In one preferred embodiment of the invention, the uro-genital condition includes infection and / or inflammation of the vagina, vulva, urinary tract, penis, and / or the rectum. In another preferred embodiment of the invention, the one or more polypeptides are dissolved in a carrier. In another preferred embodiment of the invention, the one or more polypeptides are associated with a tampon for preventing toxic shock syndrome. In another preferred embodiment, the one or more polypeptides are associated with a contraceptive for prevention of sexually transmitted diseases or infections. In another preferred embodiment, the one or more polypeptides are associated with a suppository for insertion into the vagina or rectum.

Description

PRIORITY CLAIM[0001] The present application is a utility application that claims priority to U.S. Provisional Patent Application Serial No. 60 / 126,233 entitled Antimicrobial Amino-Acid Sequences Derived from Alpha-Melanocyte Stimulating Hormone, filed Mar. 24, 1999.[0002] The present invention relates to the field of treatment for uro-genital conditions.[0003] Uro-genital conditions or diseases commonly affect both men and women. These conditions include infections and / or inflammation of the urinary system and the genital system. For example, according to the National Institute of Child Health and Human Development (NICHD), "most women will have at least one form of vaginitis in their lifetime." Vaginitis, National Institute of Child Health and Human Development--Publications On-line, (last modified Jan. 12, 2000), <http: / / www.nichd.nih.giv / publications / pubs / vag1.htm>. The causes for vaginitis range from bacterial, fungal, or viral infections to irritations from chemicals in ...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K38/06A61K38/07A61K38/34
CPCA61K9/0034A61K38/34A61K38/07A61K38/06
Inventor CATANIA, ANNA P.LIPTON, JAMES M.
Owner CATANIA ANNA P
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