Method and compositions for the direct concentrated delivery of passive immunity

• US 5,505,945 A
• Filed: 08/25/1994
• Issued: 04/09/1996
• Est. Priority Date: 01/12/1993
• Status: Expired due to Term

• Current Assignee: London Health Sciences Centre Research Incorporated, Medical Sciences Research Institute
• Original Assignee: Medical Sciences Research Institute
• Inventors: Myrvik, Quentin N., Gristina, Anthony G.
• Primary Examiner(s): Parr, Margaret
• Assistant Examiner(s): LORING, SUSAN
• Application Number:
  US08/295,482
• Time in Patent Office: 593 Days
• Field of Search: 424/164.1, 424/150.1, 424/130.1, 424/163.1, 424/165.1, 424/169.1, 424/170.1, 530/387.1, 530/388.1, 530/388.2, 530/388.4, 530/389.1, 530/389.5
• US Class Current: 424/164.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/44 Antibodies bound to carriers
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: C07K 16/12 against material from bacteria
• CPC Class Codes: C07K 16/1214 from Pseudomonadaceae (F)
• CPC Class Codes: C07K 16/1271 from Micrococcaceae (F), e.g. Staphylococcus
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compositions containing a high concentration of the full repertoire of immunoglobulins, including IgA, IgM and IgG, are used to combat infections from microorganisms and viruses at a wound, surgical, or burn site, or normal tissue times of risk of infection. The compositions can contain elevated antibody titers for several specific pathogens including S. aureus, Coagulase Negative Staphylococci Enterococci, S. epidermidis, P. aeruginosa, E. coli, and Enterobacter spp., etc. The compositions are applied directly to a wound or burn site as an ointment, creme, fluid, spray, or the like, prior to viral or bacterial attachment or biofilm formation such that adhesion of the pathogens is inhibited and the pathogens closest to the wound or burn site will be pre-opsonized for phagocytic killing prior to toxin release. The immunoglobulins in the composition can be immobilized on a biocompatible material such as collagen, fibrin, hyaluronan, biodegradable polymers, and fragments thereof, which will be placed in-situ at the wound, surgical or burn site. In addition, the immunoglobulins in the composition may be coated on the body contacting surface of an implantable device such as a catheter, contact lens or total joint. The inventive compositions have particular application in preventing infections.

Claims

1. A method for preventing infections in human and animal hosts that are derived from wounds, burns, or biomaterials, comprising the steps of:

preparing a surgical or trauma site of a wound, burn or biomaterial implant site in a human or animal host where damaged tissue exists, wherein said preparing is selected from the group consisting of cleaning, decontaminating, debriding and surgery;

directly applying an amount of an immunoglobulin composition containing a combination of IgG, IgM and IgA, wherein said composition contains elevated levels of IgM between 200-300 mg/dl and IgA between 400-500 mg/dl when compared with normal serum levels, directly on either tissue surfaces at said surgical or trauma site or on a biomaterial to be applied at said biomaterial implant site to produce an immunocompetent inflammatory zone sufficient to prevent adhesion of microorganisms to said tissue surfaces, said biomaterial implant site or a biofilm formation and to pre-opsonize said microorganisms for rapid intracellular killing by host defense mechanisms, said step of directly applying said composition occurring prior to microbial attachment to said tissue surfaces, biomaterial implant site or biofilm formation, said step of directly applying being performed by a process selected from the group consisting of applying said immunoglobulin composition to said tissue surfaces or said biomaterial implant site at a time of surgery or trauma or within a period of six hours after said surgery or trauma, or using a biomaterial pre-coated with said immunoglobulin composition; and

preventing or reducing infections in said human or animal host at said surgical or trauma site with said immunoglobulin composition or biomaterial pre-coated with said immunoglobulin composition.

2. A method as recited in claim 1 wherein said immunoglobulin composition includes immunoglobulins specific for Gram positive microorganisms.

3. A method as recited in claim 1 wherein said immunoglobulin composition includes immunoglobulins specific for Gram negative microorganisms.

4. A method for preventing infections in human and animal hosts that are derived from wounds, burns, or biomaterials, comprising the steps of:

preparing a surgical or trauma site of a wound, burn or biomaterial implant site in a human or animal host where damaged tissue exists, wherein said preparing is selected from the group consisting of cleaning, decontaminating, debriding and surgery;

directly applying an amount of an immunoglobulin composition containing a combination of IgG, IgM and IgA, wherein said composition contains elevated levels of IgM between 200-300 mg/dl and IgA between 400-500 mg/dl when compared with normal serum levels, or antibodies or monoclonal antibodies specific for a microorganism selected from the group consisting of P. aeruginosa, S. aureus, and S. epidermidis directly on either tissue surfaces at said surgical or trauma site or on a biomaterial to be applied at said biomaterial implant site to produce an immunocompetent inflammatory zone sufficient to prevent adhesion of said microorganisms to said tissue surfaces, said biomaterial implant site or a biofilm formation and to pre-opsonize said microorganisms for rapid intracellular killing by host defense mechanisms, said step of directly applying said composition occurring prior to microbial attachment to said tissue surfaces, biomaterial implant site or biofilm formation, said step of directly applying being performed by a process selected from the group consisting of applying said composition to said tissue surfaces or said biomaterial implant site at a time of surgery or trauma or within a period of six hours after said surgery or trauma, or using a biomaterial pre-coated with said composition; and

preventing or reducing infections in said human or animal host at said surgical or trauma site with said composition or biomaterial pre-coated with said composition.