WO2009152298A1 - Procédés, compositions et kits de diagnostic pour la détection et le traitement d'une colonisation staphylococcique nasale au moyen d'une achromopeptidase - Google Patents

Procédés, compositions et kits de diagnostic pour la détection et le traitement d'une colonisation staphylococcique nasale au moyen d'une achromopeptidase Download PDF

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Publication number
WO2009152298A1
WO2009152298A1 PCT/US2009/046996 US2009046996W WO2009152298A1 WO 2009152298 A1 WO2009152298 A1 WO 2009152298A1 US 2009046996 W US2009046996 W US 2009046996W WO 2009152298 A1 WO2009152298 A1 WO 2009152298A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
gram positive
treatment
achromopeptidase
nasal
Prior art date
Application number
PCT/US2009/046996
Other languages
English (en)
Inventor
Shawn Mark O'hara
Original Assignee
Zeus Scientific, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zeus Scientific, Inc. filed Critical Zeus Scientific, Inc.
Publication of WO2009152298A1 publication Critical patent/WO2009152298A1/fr

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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
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase

Definitions

  • the present invention relates to the administration of achromopeptidase (ACP) for the treatment or diagnosis of Staphylococcus Aureus (SA) infections in mammals, including humans, as well as pharmaceutical preparations used in the same treatment or diagnosis.
  • ACP achromopeptidase
  • SA Staphylococcus Aureus
  • the invention embraces the use of achromopeptidase broadly, including all recombinant forms, ACP variants from genetic mutations, and wild type form.
  • SA Staphylococcus aureus
  • MRSA methicillin-resistant Staphylococcus aureus
  • Lysostaphin an enzyme that lyses the cell walls of S.A., is effective in the treatment of established staphylococcal infections. Its action is due to a peptidase that cleaves cell wall polyglycine bridges and is found exclusively in coagulase-positive staphylococci.
  • Staphylococcal infections are a significant cause of death in the US, particularly in settings such as hospitals, nursing homes, schools, and infirmaries.
  • Patients particularly at risk include infants, the elderly, the immuno-compromised, the immuno-suppressed, those convalescing, and those with chronic conditions, requiring frequent hospital stays. Further, multiple drug resistant strains of Staphylococcus
  • SA Aureus
  • Nasal carriage of staphylococci is an important risk factor for contracting S.A. infection. Patients at greatest risk are those undergoing impatient or outpatient surgery, in an Intensive Care Unit, on continuous hemodialysis, with HIV infection, with AIDS, burn victims, people with diminished natural immunity from treatments or disease, chronically ill or debilitated patients, geriatric populations, infants with immature immune systems, and people with intravascular devices or other foreign bodies.
  • Chang et al. studied 84 patients with cirrhosis admitted to a liver transplant unit. Overall, 39 (46%) were nasal carriers of S.A. and 23% of these patients subsequently developed S.A. infections as compared to only 4% of non-carriers. A study of HIV patients showed that 49% of patients had at least one positive nasal culture of S.A.
  • MRSA methicillin resistant staphylococcus aureus
  • 6,028,051 provides for a therapeutic regimen of a single or short course of lysostaphin administration using relatively high doses. This method provides for effective therapy. However, the use of high doses of lysostaphin as an intranasal application may involve higher than acceptable risks.
  • This invention relates to compositions that comprise ACP for use in the intranasal treatment of disease, and methods for use of such compositions.
  • Achromopeptidase is known to have potent bacteriolytic activity for most of the gram-positive aerobic bacteria, and is also used for the lysis of anaerobic cocci. It has also been used for the lysis of S.A. and streptococcus faecalis.
  • the present invention takes advantage of such lysis ability, and provides an advantageous method of lysing S.A. in nasal carriages.
  • the method provided by the invention offers a number of advantages, including that the compositions of the invention that it uses can be simply, quickly, and safely applied to the nasal carriage for effective treatment.
  • Diagnostic kits comprising the compositions provided by the invention are also contemplated, and can be used for practicing the advantageous methods provided thereby.
  • the process provided by the invention is particularly advantageous since only a single step or a few steps are involved. It has the advantage of being expedient compared to prior processes, and in its practice requires little instrumentation to achieve the advantages sought.
  • ACP which can effectively lyse bacteria such as mycobacteria, provides an unexpected advantage of being effective and safe in the nasal carriage.
  • Figure 1 is a flow chart depicting a general outline of steps in obtaining decolonization using ACP.
  • the present invention embodies a rapid, safe, and inexpens ive method for topical application of ACP.
  • the practic e of this me thod can result in signi ficant decolonization and subsequent reduction and elimination of S.A. colonization.
  • the present invention further encompasses the same method and topical application for other staphylococci infections such as, but not limited to, staphylococcal epidermidis.
  • the method of the invention inv olves the purification of ACP to a sufficient purity level to be therapeutic ally effective for this purpose. Purification can be by any means known in the art.
  • the purified ACP is us ed in a formulation that is optimized to determined an effectiv e concentration and v iscosity for nasal applic ations.
  • F or topical delivery to the anterior nares the present invention contemplates formulations that include saline, buffered saline, ointments, and creams. Delivery of the formulation c an be accomplishedby any means known in the art.
  • Example 1 a nasal spray or swab ointment or cream, applied through a coated finger and sp read in the nares are the preferred modes.
  • the following examples demonstrate the ability of ACP to provide effective disruption of the cell wall of S.A. and potential decolonizati on in the n asal carriage, i n accordance with the present invention.
  • Achromopeptidase Disruption of the SA Cell Wall is Compatible with Direct- PCR & Nasal swab samples containing PCR inhibitors
  • Nasal samples were obtained from nasal swabs after elution with 200 micro liters of TE. Samples were then inc ubated with or without achromopeptidase (ACP) incubation at 1 Unit/ul 37C for 15 minutes followed by 99C for 5 minutes. Direct T aqMan PCR amplification of an exogenous spiked in control template DNA at a volume of up to 2. 5 micro liters of this ACP lysate in a 25 micro liter PCR r eaction confirmed compatibility . Further, transfer of volumes greater than 2.5ul into the 25ul PCR showed inhibition from both sample types suggesting that inhibition might start to negatively effect PCR above this volume proportion if not removed.
  • ACP achromopeptidase
  • ACP Direct PCR from nasal swab sam ples can be improved by removal of PCR inhibitors using methods such as cell or DNA enrichment, activated charcoal etc. as described in the body of the text.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne des compositions d'achromopeptidase et autres compositions apparentées à usage intranasal qui peuvent être administrées aux narines antérieures du nez et appliquées par tout moyen au portage nasal de sujets à risque de colonisation nasale par des staphylocoques et d'une infection ultérieure. Cette invention concerne également des procédés pour leur utilisation, ainsi que des kits de diagnostic utiles pour mettre en œuvre ces procédés.
PCT/US2009/046996 2008-06-13 2009-06-11 Procédés, compositions et kits de diagnostic pour la détection et le traitement d'une colonisation staphylococcique nasale au moyen d'une achromopeptidase WO2009152298A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6114508P 2008-06-13 2008-06-13
US61/061,145 2008-06-13

Publications (1)

Publication Number Publication Date
WO2009152298A1 true WO2009152298A1 (fr) 2009-12-17

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/046996 WO2009152298A1 (fr) 2008-06-13 2009-06-11 Procédés, compositions et kits de diagnostic pour la détection et le traitement d'une colonisation staphylococcique nasale au moyen d'une achromopeptidase

Country Status (1)

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WO (1) WO2009152298A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5770375A (en) * 1992-07-07 1998-06-23 Tsuneya Ohno Probe for diagnosing staphylococcus epidermidis
US20030211995A1 (en) * 2001-12-21 2003-11-13 Kokai-Kun John Fitzgerald Methods and formulations for eradicating or alleviating staphylococcal nasal colonization using lysostaphin
US20060246055A1 (en) * 1999-03-05 2006-11-02 Nutrition 21 Compositions and methods for treatment of staphylococcal infection while suppressing formation of antibiotic-resistant strains

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5770375A (en) * 1992-07-07 1998-06-23 Tsuneya Ohno Probe for diagnosing staphylococcus epidermidis
US20060246055A1 (en) * 1999-03-05 2006-11-02 Nutrition 21 Compositions and methods for treatment of staphylococcal infection while suppressing formation of antibiotic-resistant strains
US20030211995A1 (en) * 2001-12-21 2003-11-13 Kokai-Kun John Fitzgerald Methods and formulations for eradicating or alleviating staphylococcal nasal colonization using lysostaphin

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