WO2000059527A1 - Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone - Google Patents
Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone Download PDFInfo
- Publication number
- WO2000059527A1 WO2000059527A1 PCT/US2000/006917 US0006917W WO0059527A1 WO 2000059527 A1 WO2000059527 A1 WO 2000059527A1 US 0006917 W US0006917 W US 0006917W WO 0059527 A1 WO0059527 A1 WO 0059527A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antimicrobial agent
- amino acid
- acid sequence
- group
- peptides
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A61K38/34—Melanocyte stimulating hormone [MSH], e.g. alpha- or beta-melanotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
Definitions
- the present invention relates to new pharmaceutical compositions useful as antimicrobial agents, including, for example, for use in reducing the viability of microbes, reducing the germination of yeasts, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation in which there is microbial infection without reducing microbial killing, and for increasing the accumulation of cAMP in microbes. More particularly, this invention relates to antimicrobial agents including amino acid sequences derived from alpha-melanocyte-stimulating hormone ( ⁇ -MSH) and biologically functional equivalents thereof. BACKGROUND OF THE INVENTION
- Mucosal secretions, phagocytes, and other components of the nonspecific (innate) host defense system initiate the response to microbial penetration before time-consuming adaptive immunity starts. Survival of plants and invertebrates, which lack adaptive immunity, illustrates effectiveness of host defense based on such innate mechanisms.
- Endogenous antimicrobial peptides are significant in epithelia, the barrier to environmental challenge that provides the first line of defense against pathogens. Production of natural antimicrobial peptides by phagocytes has been recognized for a long time. These natural antimicrobial peptides generally have a broad spectrum of activity against bacteria, fungi, and viruses. Martin, E., Ganz, T., Lehrer, R.I., Defensins and Other Endogenous Peptide Antibiotics of
- BPI bactericidal/permeability-increasing protein
- Alpha-melanocyte-stimulating hormone (“ ⁇ -MSH”) is an ancient 13 amino acid peptide produced by post-translational processing of the larger precursor molecule proopiomelanocortin and shares the 1-13 amino acid sequence with adrenocorticotropic hormone (“ACTH”). Eberle, A. N., The Melanotropins. Karger, Basel, Switzerland (1988). ⁇ -MSH is known to be secreted by many cell types including pituitary cells, monocytes, melanocytes, and keratinocytes. Lipton, J. M.,
- ⁇ -MSH occurs in the skin of rats and in the human epidermis. Thody, A.J., Ridley, K., Penny, R.J., Chalmers, R., Fisher, C, Shuster, S., MSH Peptides Are Present in Mammalian Skin. Peptides 4, 813-816 (1983). ⁇ -MSH is also found in the mucosal barrier of the gastrointestinal tract in intact and hypophysectomized rats. Fox, J.A.E.T., Kraicer, J.,
- ⁇ -Melanocvte Stimulating Hormone its Distribution in the Gastrointestinal Tract of Intact and Hypophysectomized Rats, Life. Sci.28, 2127-2132 (1981).
- human duodenal cells produce ⁇ -MSH in culture.
- Catania et al. unpublished.
- ⁇ -Melanocyte-stimulating hormone is known to have potent antipyretic and anti-inflammatory properties.
- ⁇ -MSH reduces production of proinflammatory mediators by host cells in vitro. Rajora, N., Ceriani, G., Catania, A., Star, R.A., Murphy, M. T., Lipton, J. M., ⁇ -MSH Production, Receptors, and Influence on
- Neopterin in a Human Monocyte/macrophage Cell Line. J. Leukoc. Biol. 59, 248-253 (1996); Star, R.A, Rajora, N., Huang, J., Stock, R.C., Catania, A., Lipton, J. M., Evidence of Autocrine Modulation of Macrophage Nitric Oxide Synthase by ⁇ -MSH, Proc. Natl. Acad. Sci. (USA) 92, 8016-8020 (1995). ⁇ -MSH also reduces production of local and systemic reactions in animal models of inflammation. Lipton, J. M., Ceriani, G., Macaluso, A., McCoy, D., Carnes, K., Biltz, J., Catania,
- ⁇ -MSH and certain other amino acid sequences derived from ⁇ -MSH have significant antimicrobial uses, including for example, for use in reducing the viability of microbes, reducing the germination of yeasts, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation in which there is microbial infection without reducing microbial killing, and increasing the accumulation of cAMP in microbes.
- the antimicrobial agent is selected from the group consisting of one or more peptides including the C-terminal amino acid sequence of ⁇ -MSH, that is, KPV, one or more peptides including the amino acid sequence MEHFRWG, or a biologically functional equivalent of any of the foregoing.
- the antimicrobial agent is selected from the group consisting of one or more peptides including the C-terminal amino acid sequence of ⁇ -MSH, that is,
- KPV or a biologically functional equivalent of any of the foregoing.
- the KPV sequence is the amino acid sequence ⁇ -MSH (11-13).
- This type of antimicrobial agent includes a dimer of the amino acid sequence KPV, such as VPKCCKPV.
- the antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence HFRWGKPV or a biologically functional equivalent of any of the foregoing.
- the HFRWGKPV sequence is the amino acid sequence ⁇ -MSH (6-13).
- the antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence SYSMEHFRWGKPV or a biologically functional equivalent of any of the foregoing.
- the SYSMEHFRWGKPV sequence is the entire amino acid sequence of ⁇ -MSH (1-13).
- the antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence MEHFRWG or a biologically functional equivalent of any of the foregoing.
- the MEHFRWG sequence is sometimes referred to as the "core" amino acid sequence of ⁇ -MSH, that is, ⁇ -MSH (4-10).
- the antimicrobial agent is further selected from the group consisting of one or more peptides having an amino acid chain length of up to thirteen. Still more preferably, the antimicrobial agent is further selected from the group consisting of one or more peptides having an amino acid chain length of up to eight. Based on the experimental results obtained thus far, the tripeptide KPV is the most effective.
- an effective concentration of the antimicrobial agent is at least 10 "12 molar, and more preferably the concentration of the antimicrobial agent is at least 10 "6 molar. It is fully expected that these peptides, which have extremely low toxicity, will be effective in animal and human subjects without adverse effect.
- Figure 2 shows that treatment with urokinase increases S. aureus colony formation, but that the addition of ⁇ -MSH (1-13) or (11-13) significantly inhibited this urokinase-enhancing effect. *p ⁇ 0.001 vs urokinase alone.
- Figure 3 shows the effect of ⁇ -MSH (1-13), ⁇ -MSH (11-13), and the "KPV dimer” on C. albicans colony forming" units ("CFU") compared to controls. All thre ⁇ molecules significantly decreased C. albicans colony forming units over a broad range of peptide concentrations.
- Figure 4 shows a comparison of candidacidal activity of certain melanocortin peptides and fluconazole (all 10 "6 M).
- the most effective of the melanocortin peptides were those including the C- terminal amino acid sequence of ⁇ -MSH, for example, ⁇ -MSH (1-13), ⁇ -MSH (6-13), and ⁇ -MSH (11-13).
- Figure 5A shows untreated germination of C. albicans, i.e, blastospores.
- Figure 5B shows horse serum-induced germination of C. albicans.
- Figure 5C shows'the effect of ⁇ -MSH (1-13) treatment on germination of C. albicans.
- Figure 5D shows the effect of ⁇ -MSH (11-13) treatment on germination of C. albicans.
- Figure 6 shows the effect of ⁇ -MSH (1-13) and ⁇ -MSH (11-13) on C. albicans killing by human neutrophils. Values are expressed as percent increase in killing vs medium alone. Scores are means + SEM.
- Figure 7 shows the effect of ⁇ -MSH (1-13), ⁇ -MSH (11-13), and forskolin on cAMP content of C. albicans.
- Figure 8 shows the inhibitory effect of ⁇ -MSH (1-13), ⁇ -MSH (11-13), and forskolin on C. albicans colony forming units.
- the peptides used in this research included: ⁇ -MSH (1-13), (4-10), (6-13), and (11-13), all of which were N-acetylated and C-amidated, and ACTH (1-39) and (18-39) (CLIP).
- Another peptide used in this research included a dimer of the amino acid sequence KPV, specifically VPKCCKPV, which also was N-acetylated and C-amidated (the "KPV dimer").
- the KPV dimer can be chemically represented as NH 2 -Lys-Pro-Val-AcCys-CysAc-Val-Pro-Lys-NH 2 .
- the peptides were prepared by solid-phase peptide synthesis and purified by reversed-phase high performance liquid chromatography, as kindly provided by Dr. Renato Longhi, CNR, Milano.
- S. aureus (ATCC 29213) and C. albicans (clinical isolate) were obtained from the collection of the Department of Microbiology, Ospedale Maggiore di Milano. C. albicans were maintained on Sabouraud' s agar slants and periodically transferred to Sabouraud' s agar plates and incubated for 48 hours at 28°C.
- To prepare stationary growth phase yeast a colony was taken from the agar plate and transferred into 30 ml Sabouraud-dextrose broth and incubated for 72 hours at 32°C. Cells were centrifuged at 1000 x g for 10 minutes and the pellet was washed twice with distilled water.
- HBSS Hank' s balanced salt solution
- S. aureus (lxl0 6 /ml in HBSS) was incubated in the presence or absence of ⁇ -MSH (1-13), ⁇ -MSH (11-13), or the "KPV dimer" at concentrations in the range of 10 "15 to 10 "4 M for 2 hours at
- Organism viability was estimated from the number of colonies formed.
- C. albicans (lxl0 /ml in HBSS) was incubated in the presence or absence of ⁇ -MSH (1-13), ⁇ -MSH (11-13), or the "KPV dimer" at concentrations in the range of 10 "15 to 10 "4 M for 2 hours at
- Organism viability was estimated from the number of colonies formed.
- Organisms were then incubated with neutrophils in presence of medium alone or
- sodium desoxycholate solution was added to the suspension and the tubes were shaken for 5 min.
- HBSS HBSS were made to obtain a final suspension of 100 cells/ml. Aliquots of 1 ml were dispensed on blood agar plates and incubated for 48 hours at 37°C. Colony forming units ("CFU") were counted at the end of the incubation period. Experiments were run in triplicate and repeated using blood from 5 different donors.
- C. albicans (lOVml), permeabilized with toluene/ethanol, were incubated at 37°C with continuous shaking in the presence of 10 "6 M ⁇ -MSH (1-13), (11-13), forskolin, an agent known to increase intracellular cAMP, or in medium alone. The reaction was stopped after 3 minutes by the addition of ice cold ethanol. cAMP was measured in duplicate using a commercial enzyme immunoassay (EIA) kit (Amersham, United Kingdom) after extraction via the liquid-phase method according to manufacturer's instructions. The effect of forskolin (10 ⁇ 6 M) on C. albicans colony formation was determined using the same procedures as for ⁇ -MSH peptides.
- EIA enzyme immunoassay
- C. albicans colony forming units were greatly reduced by ⁇ -MSH (1-13) and (11- 13) (Fig. 3).
- a dimer of the amino acid sequence KPV, specifically, KPVCCVPK also inhibited C. albicans colony formation (Fig. 3).
- ⁇ -MSH peptides increased cAMP accumulation Because many of the effects of ⁇ -MSH are known to be mediated by induction of cAMP, we measured effects of ⁇ -MSH peptides on cAMP accumulation in C. albicans. ⁇ -MSH (1-13) and (11-13) enhanced cAMP content in the yeast (Fig.7). The increase was of the same order of magnitude as that induced by equimolar forskolin, an adenylate cyclase activator (Figs. 7). To determine whether increases in cAMP could be responsible for reduction in CFU, we tested the effects of forskolin on C. albicans viability. Results showed that 10 "6 M forskolin markedly inhibited
- ⁇ -MSH peptides were those including the C- terminal amino acid sequence KPV of the ⁇ -MSH sequence, i.e., ⁇ -MSH (1-13), (6-13), and (11-
- a dimer of the amino acid sequence KPV specifically, VPKCCKPV (referred to herein as the "KPV dimer") has also been shown to be at least as effective as ⁇ -MSH (11-13) against microbes.
- the ⁇ -MSH "core” sequence (4-10) which is known to influence learning and memory, but has little
- antimicrobial activity is not common to all melanocortin peptides, but rather that it is specific to ⁇ - MSH amino acid sequences, and most particularly to the C-terminal amino-acid sequences of ⁇ - MSH.
- ⁇ -MSH has a physiological role in natural immunity.
- these peptides that likewise have anti-inflammatory activity could be used to treat cases in which both inflammation and microbial invasion coexist, or where the aim is to prevent their
- Yeasts can be major pathogens.
- C. albicans is the leading cause of invasive fungal disease in premature infants, diabetics, surgical patients, and patients with human immunodeficiency virus infection or other immunosuppressed conditions.
- death resulting from systemic C. albicans infection in immunocompromised patients is substantial.
- albicans infection involves adhesion to host epithelial and endothelial cells and morphologic switching of yeast cells from the ellipsoid blastospore to various filamentous forms: germ tubes, pseudohyphae, and hyphae. Gow, N.A., Germ Tube Growth of Candida Albicans. Curr. Topics Med. Mycol. 8, 43-55 (1997). It is therefore important that ⁇ -MSH (1-13) and its C-terminal tripeptide (11-13) not only reduce the viability of yeast, but also reduce germination of yeast.
- ⁇ -MSH has potent anti-inflammatory influences in models of acute, chronic, and systemic inflammation. Its wide spectrum of activity and low toxicity suggest that ⁇ -MSH is useful for treatment of inflammation in human and veterinary disorders. It was, therefore, important to learn the influence of ⁇ -MSH peptides on C. albicans killing by phagocytes. This is especially important because ⁇ -MSH is known to inhibit neutrophil chemotaxis.
- ⁇ -MSH peptides exert their antimicrobial effects and whether they operate like other natural antimicrobial agents. It is known that ⁇ -MSH shares a number of similarities with other natural antimicrobial peptides such as the defensins or the cathelicidins:
- proopiomelanocortin (POMC) is expressed in phagocytes and epithelia and post-translational proteolytic processing is required to convert it to active ⁇ -MSH.
- PMC proopiomelanocortin
- ⁇ -MSH inhibits HIV-1 replication in acutely and chronically infected monocytes. Barcellini, W., La Maestra, L., Clerici, G., Lipton, J. M., Catania, A., Inhibitory Influences of ⁇ -MSH Peptides on Hiv-1 Expression in Monocytic Cells, 12th World AIDS Conference, Geneva, June 28-July 3, 1998. These findings indicate that ⁇ -MSH has the broad spectrum of activity of other innate antimicrobial substances. The mechanism of action of natural antimicrobial agents is only partly understood.
- cAMP-enhancing agents inhibit mRNA and protein synthesis in C. albicans. Bhattacharya, A., Datta, A., Effect of Cyclic AMP on RNA and Protein Synthesis in Candida Albicans. Biochem. Biophys. Res. Commun. 77:1483-44 (1977).
- a biological functional equivalent is defined as an amino acid sequence that is functionally equivalent in terms of biological activity.
- amino acid sequences described here are effective, it is clear to those familiar with the art that amino acids can be substituted in the amino acid sequence or deleted without altering the effectiveness of the peptides. Further, it is known that stabilization of the ⁇ -
- MSH sequence can greatly increase the activity of the peptide and that substitution of D- amino acid
- L-forms can improve or decrease the effectiveness of peptides.
- a stable analog of ⁇ -MSH ,[Nle 4 ,D-Phe 7 ]- ⁇ -MSH which is known to have marked biological activity on
- melanocytes and melanoma cells is approximately 10 times more potent than the parent peptide in
- amino acids having similar hydropathic values can be substituted for valine, which has a hydropathic index of +4.2, and still obtain a protein having like biological activity.
- lysine (-3.9) can be substituted for arginine (-4.5), and so on.
- amino acids can be successfully substituted where such amino acid has a hydropathic score of within about +/- 1 hydropathic index unit of the replaced amino acid.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Zoology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicinal Preparation (AREA)
- Orthopedics, Nursing, And Contraception (AREA)
- Prostheses (AREA)
- Lubricants (AREA)
- Photoreceptors In Electrophotography (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002368387A CA2368387A1 (en) | 1999-03-24 | 2000-03-17 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
DE60036800T DE60036800T2 (en) | 1999-03-24 | 2000-03-17 | ANTIMICROBIAL AMINO ACID SEQUENCES FROM ALPHA MELANOCYTE STIMULATING HORMONE |
AU36293/00A AU3629300A (en) | 1999-03-24 | 2000-03-17 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
EP00914980A EP1191939B1 (en) | 1999-03-24 | 2000-03-17 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
DK00914980T DK1191939T3 (en) | 1999-03-24 | 2000-03-17 | Antimicrobial amino acid sequences derived from alpha-melanocyte stimulating hormone |
JP2000609090A JP4767418B2 (en) | 1999-03-24 | 2000-03-17 | Antibacterial amino acid sequence derived from alpha-melanocyte-stimulating hormone |
US09/533,341 US6803044B1 (en) | 1999-03-24 | 2000-03-23 | Antimicrobial and anti-inflammatory peptides for use in human immunodeficiency virus |
US09/957,765 US6887846B2 (en) | 1999-03-24 | 2001-09-21 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
HK02105887.3A HK1044287A1 (en) | 1999-03-24 | 2002-08-12 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
US11/121,166 US20060111300A1 (en) | 1999-03-24 | 2005-05-02 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12623399P | 1999-03-24 | 1999-03-24 | |
US60/126,233 | 1999-03-24 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/533,341 Continuation US6803044B1 (en) | 1999-03-24 | 2000-03-23 | Antimicrobial and anti-inflammatory peptides for use in human immunodeficiency virus |
US09/957,765 Continuation US6887846B2 (en) | 1999-03-24 | 2001-09-21 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000059527A1 true WO2000059527A1 (en) | 2000-10-12 |
Family
ID=22423735
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/006917 WO2000059527A1 (en) | 1999-03-24 | 2000-03-17 | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
PCT/US2000/007846 WO2000056353A2 (en) | 1999-03-24 | 2000-03-23 | A uro-genital condition treatment system |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/007846 WO2000056353A2 (en) | 1999-03-24 | 2000-03-23 | A uro-genital condition treatment system |
Country Status (14)
Country | Link |
---|---|
EP (3) | EP1191939B1 (en) |
JP (2) | JP4767418B2 (en) |
KR (1) | KR20020000791A (en) |
CN (4) | CN101249258A (en) |
AT (3) | ATE375801T1 (en) |
AU (3) | AU3629300A (en) |
CA (2) | CA2368387A1 (en) |
CY (1) | CY1107137T1 (en) |
DE (3) | DE60036800T2 (en) |
DK (3) | DK1191939T3 (en) |
ES (3) | ES2295016T3 (en) |
HK (2) | HK1040496B (en) |
PT (2) | PT1191939E (en) |
WO (2) | WO2000059527A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001098362A2 (en) * | 2000-06-16 | 2001-12-27 | Hercules Incorporated | Chemically-modified antimicrobial peptides, compositions and methods of production and use |
WO2003051390A1 (en) * | 2001-12-17 | 2003-06-26 | Zengen, Inc. | Use of a polypeptide for treatment of pruritus in animals |
WO2004058804A1 (en) * | 2002-12-24 | 2004-07-15 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
WO2006088010A1 (en) | 2005-02-15 | 2006-08-24 | Toagosei Co., Ltd. | Antimicrobial peptide and use thereof |
US7135548B2 (en) * | 2002-11-14 | 2006-11-14 | Zengen, Inc. | Modified α-MSH peptides and derivatives thereof |
US7615534B2 (en) | 2004-07-30 | 2009-11-10 | Toagosei Co., Ltd | Antimicrobial peptides and use thereof |
US7674771B2 (en) | 2003-10-29 | 2010-03-09 | Toagosei Co., Ltd | Antimicrobial peptides and utilization of the same |
US7964556B1 (en) | 2004-12-06 | 2011-06-21 | Toagosei Co., Ltd | Antimicrobial peptides and use thereof |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6887846B2 (en) | 1999-03-24 | 2005-05-03 | Zengen, Inc. | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone |
US7402559B2 (en) * | 1999-03-24 | 2008-07-22 | Msh Pharma, Incorporated | Composition and method of treatment for urogenital conditions |
US6800291B1 (en) | 1999-03-24 | 2004-10-05 | Zengen, Inc. | Uro-genital condition treatment system |
US6780838B2 (en) * | 2001-01-29 | 2004-08-24 | Zengen, Inc. | Compounds for treating fungal pathologies of the oral cavity |
US6894028B2 (en) | 2001-04-06 | 2005-05-17 | Zengen, Inc. | Use of KPV tripeptide for dermatological disorders |
US7115574B2 (en) | 2001-12-10 | 2006-10-03 | Zengen, Inc. | System and method for support legacy operating system booting in a legacy-free system |
US20090232866A1 (en) * | 2003-10-07 | 2009-09-17 | Mariann Pavone-Gyongyosi | Oligopeptides as coating material for medical products |
CN100390194C (en) * | 2004-02-27 | 2008-05-28 | 沛进生物科技股份有限公司 | Low hemolytic antibacterial peptide and its application |
WO2006071822A1 (en) * | 2004-12-23 | 2006-07-06 | Regents Of The University Of Minnesota | Exotoxin inhibitory factor |
DK2018164T3 (en) | 2006-05-12 | 2017-06-12 | Christian Noe | Use of combination preparations comprising antimycotics |
WO2008157205A2 (en) * | 2007-06-15 | 2008-12-24 | Duke University | Methods and compositions for treating urinary tract infections using agents that mimic or elevate cyclic amp |
AU2008310059A1 (en) * | 2007-09-11 | 2009-04-16 | Mondobiotech Laboratories Ag | Use of a peptide as a therapeutic agent |
WO2009033812A2 (en) * | 2007-09-11 | 2009-03-19 | Mondobiotech Laboratories Ag | Use of a combination of neuropeptide-ff and alpha-msh as a therapeutic agent |
JP2010539037A (en) * | 2007-09-11 | 2010-12-16 | モンドバイオテック ラボラトリーズ アクチエンゲゼルシャフト | Use of peptides as therapeutic agents |
EP2508198B1 (en) | 2011-04-07 | 2014-08-27 | Fresenius Medical Care Deutschland GmbH | Peptides for suppressing inflammation reactions in hemodialysis |
SE539566C2 (en) * | 2014-09-03 | 2017-10-10 | Danell Nils | Device for the detection of gaseous amines from disease in the human urogential system |
CN112689471A (en) * | 2018-07-12 | 2021-04-20 | 普瑞玛太普公司 | Vaginal temperature sensing device and method |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5739111A (en) * | 1995-04-28 | 1998-04-14 | Societe L'oreal S.A. | Modulating body/cranial hair growth with derivatives of the α-type melanocyte-stimulating hormone |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH422813A (en) * | 1960-11-17 | 1966-10-31 | Ciba Geigy | Process for the production of new polypeptides |
CH444178A (en) * | 1963-05-20 | 1967-09-30 | Ciba Geigy | Process for the production of B-MSH |
US5157023A (en) | 1984-08-21 | 1992-10-20 | Lipton James M | Antipyretic and anti-inflammatory lys pro val compositions and method of use |
US5028592A (en) | 1986-08-08 | 1991-07-02 | Lipton James M | Antipyretic and anti-inflammatory peptides |
ATE84420T1 (en) * | 1986-02-03 | 1993-01-15 | University Patents Inc | METHODS OF STIMULATION OF MELANOCYTES BY LOCAL APPLICATION OF ALPHA-MSH ANALOGUES, AND COMPOSITIONS. |
IL89770A (en) * | 1988-03-28 | 1994-12-29 | British Tech Group | Analgesic peptides and pharmaceutical compositions containing them and the process for the preparation of some such compounds |
-
2000
- 2000-03-17 EP EP00914980A patent/EP1191939B1/en not_active Expired - Lifetime
- 2000-03-17 CA CA002368387A patent/CA2368387A1/en not_active Abandoned
- 2000-03-17 WO PCT/US2000/006917 patent/WO2000059527A1/en active IP Right Grant
- 2000-03-17 ES ES00914980T patent/ES2295016T3/en not_active Expired - Lifetime
- 2000-03-17 DK DK00914980T patent/DK1191939T3/en active
- 2000-03-17 PT PT00914980T patent/PT1191939E/en unknown
- 2000-03-17 DE DE60036800T patent/DE60036800T2/en not_active Expired - Lifetime
- 2000-03-17 JP JP2000609090A patent/JP4767418B2/en not_active Expired - Fee Related
- 2000-03-17 AU AU36293/00A patent/AU3629300A/en not_active Abandoned
- 2000-03-17 AT AT00914980T patent/ATE375801T1/en active
- 2000-03-23 KR KR1020017012104A patent/KR20020000791A/en not_active Application Discontinuation
- 2000-03-23 WO PCT/US2000/007846 patent/WO2000056353A2/en not_active Application Discontinuation
- 2000-03-23 DK DK03029246.0T patent/DK1433485T3/en active
- 2000-03-23 DE DE60043358T patent/DE60043358D1/en not_active Expired - Lifetime
- 2000-03-23 CN CNA2007101945446A patent/CN101249258A/en active Pending
- 2000-03-23 PT PT03029246T patent/PT1433485E/en unknown
- 2000-03-23 CA CA002367118A patent/CA2367118A1/en not_active Abandoned
- 2000-03-23 ES ES00916651T patent/ES2251982T3/en not_active Expired - Lifetime
- 2000-03-23 AT AT03029246T patent/ATE448790T1/en active
- 2000-03-23 EP EP03029246A patent/EP1433485B1/en not_active Expired - Lifetime
- 2000-03-23 AU AU37725/00A patent/AU776804C/en not_active Ceased
- 2000-03-23 DE DE60023667T patent/DE60023667T2/en not_active Expired - Lifetime
- 2000-03-23 EP EP00916651A patent/EP1165120B1/en not_active Expired - Lifetime
- 2000-03-23 CN CNB008079536A patent/CN100371019C/en not_active Expired - Fee Related
- 2000-03-23 ES ES03029246T patent/ES2336661T3/en not_active Expired - Lifetime
- 2000-03-23 AT AT00916651T patent/ATE308338T1/en active
- 2000-03-23 CN CNA2004100380191A patent/CN1544461A/en active Pending
- 2000-03-23 DK DK00916651T patent/DK1165120T3/en active
- 2000-03-23 CN CNA2007101667262A patent/CN101240017A/en active Pending
- 2000-03-23 JP JP2000606257A patent/JP4057787B2/en not_active Expired - Fee Related
-
2002
- 2002-03-18 HK HK02102044.0A patent/HK1040496B/en not_active IP Right Cessation
- 2002-08-12 HK HK02105887.3A patent/HK1044287A1/en unknown
-
2004
- 2004-12-23 AU AU2004242451A patent/AU2004242451A1/en not_active Abandoned
-
2008
- 2008-01-14 CY CY20081100049T patent/CY1107137T1/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5739111A (en) * | 1995-04-28 | 1998-04-14 | Societe L'oreal S.A. | Modulating body/cranial hair growth with derivatives of the α-type melanocyte-stimulating hormone |
Non-Patent Citations (9)
Title |
---|
CUTULI ET AL.: "Antimicrobial effects of alpha-MSH peptides", J. LEUKOCYTE BIOL.,, vol. 67, no. 2, February 2000 (2000-02-01), pages 233 - 239, XP002931058 * |
DEETER ET AL.: "Antipyretic properties of centrally administered alpha-MSH fragments in the rabbit", PEPTIDES,, vol. 9, 1989, pages 1285 - 1288, XP002931079 * |
GETTING ET AL.: "POMC gene-derived peptides activate melanocortin type-3 receptor op murine macrophage, suppress cytokine release and inhibit neutrophil migration in acute experimental inflammation", J. IMMUNOL.,, vol. 162, no. 12, 15 June 1999 (1999-06-15), pages 7446 - 7453, XP002931098 * |
HARRIS ET AL.: "Alpha-melanocyte stimulating hormone (alpha-MSH) and melanin concentrating hormone (MCH) stimulate phagocytosis by head kidney leucocytes of rainbow trout (Oncoryhnchus mykiss) in vitro", FISH & SHELLFISH IMMUNOL.,, vol. 8, no. 8, November 1998 (1998-11-01), pages 631 - 638, XP002931054 * |
HILTZ ET AL.: "Alpha-MSH peptides inhibit acute inflammation and contact sensitivity", PEPTIDES,, vol. 11, no. 5, 1990, pages 979 - 982, XP002931099 * |
HUANG ET AL.: "Role of central melanocortins in endotoxin-induced anorexia", AM. J. PHYSIOL., (REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY. 45),, vol. 276, no. 3, 1999, pages R864 - R871, XP002931080 * |
LIPTON ET AL.: "Mechanisms of antiinflammatory action of the neuro immunomodulatory peptide alpha-MSH", ANNALS OF THE N.Y. ACAD. SCI.,, vol. 840, 1 May 1998 (1998-05-01), pages 373 - 380, XP002931100 * |
RICHARDS ET AL.: "Effect of alpha-MSH 11-13 (Lysine-proline-valine) on fever in the rabbit", PEPTIDES,, vol. 5, 1984, pages 815 - 817, XP002931055 * |
WEISS ET AL.: "Corticotropin-peptide regulation of intracellular cyclic-AMP production in cortical neurons in primary culture", J. NEUROCHEM.,, vol. 45, no. 3, 1985, pages 869 - 874, XP002931056 * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001098362A2 (en) * | 2000-06-16 | 2001-12-27 | Hercules Incorporated | Chemically-modified antimicrobial peptides, compositions and methods of production and use |
WO2001098362A3 (en) * | 2000-06-16 | 2002-12-05 | Hercules Inc | Chemically-modified antimicrobial peptides, compositions and methods of production and use |
US6858581B2 (en) | 2000-06-16 | 2005-02-22 | Arizona State University | Chemically-modified peptides, compositions, and methods of production and use |
WO2003051390A1 (en) * | 2001-12-17 | 2003-06-26 | Zengen, Inc. | Use of a polypeptide for treatment of pruritus in animals |
US6939846B2 (en) | 2001-12-17 | 2005-09-06 | Zengen, Inc. | Use of a polypeptide for treatment of pruritis in animals |
US6969590B2 (en) | 2001-12-17 | 2005-11-29 | Zengen, Inc. | Use of a polypeptide for treatment of pruritus in animals |
US7135548B2 (en) * | 2002-11-14 | 2006-11-14 | Zengen, Inc. | Modified α-MSH peptides and derivatives thereof |
WO2004058804A1 (en) * | 2002-12-24 | 2004-07-15 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
US7674771B2 (en) | 2003-10-29 | 2010-03-09 | Toagosei Co., Ltd | Antimicrobial peptides and utilization of the same |
US7615534B2 (en) | 2004-07-30 | 2009-11-10 | Toagosei Co., Ltd | Antimicrobial peptides and use thereof |
US7964556B1 (en) | 2004-12-06 | 2011-06-21 | Toagosei Co., Ltd | Antimicrobial peptides and use thereof |
WO2006088010A1 (en) | 2005-02-15 | 2006-08-24 | Toagosei Co., Ltd. | Antimicrobial peptide and use thereof |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1191939B1 (en) | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone | |
US20060111300A1 (en) | Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulating hormone | |
US6803044B1 (en) | Antimicrobial and anti-inflammatory peptides for use in human immunodeficiency virus | |
US6780838B2 (en) | Compounds for treating fungal pathologies of the oral cavity | |
Cutuli et al. | Antimicrobial effects of α‐MSH peptides | |
EP1853620B1 (en) | Antimicrobial hexapeptides | |
Casciaro et al. | Promising approaches to optimize the biological properties of the antimicrobial peptide esculentin-1a (1–21) NH2: amino acids substitution and conjugation to nanoparticles | |
De Lucca et al. | Antifungal peptides: origin, activity, and therapeutic potential | |
US7115574B2 (en) | System and method for support legacy operating system booting in a legacy-free system | |
CA2542303A1 (en) | A composition and method of treatment for urogenital conditions | |
US20050130901A1 (en) | Modified alpha-MSH peptides and derivatives thereof | |
EP1471932A1 (en) | Use of a polypeptide for treatment of pruritus in animals | |
WO2004046166A2 (en) | Modified alpha-msh peptides and derivatives thereof | |
US20030176353A1 (en) | Lys-pro-val dimer, formulations and applications | |
US8513381B2 (en) | Melanocortin analogs with antimicrobial activity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 09957765 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 2368387 Country of ref document: CA Ref country code: CA Ref document number: 2368387 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000914980 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 2000914980 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 2000914980 Country of ref document: EP |