Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2001-11-27
2004-04-06
Spivack, Phyllis G. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S012200
Reexamination Certificate
active
06716813
ABSTRACT:
FIELD OF THE INVENTION
The invention relates generally to the use of human beta defensins, lysozyme, and lactoferrin as a new class of non-antibiotic antimicrobials. More specifically, the invention relates to the use of these antimicrobials for the treatment of otitis media and paranasal sinusitis.
BACKGROUND OF THE INVENTION
The rapid worldwide increase in antibiotic resistance among pathogens has given rise to an urgent need to develop new and innovative non-antibiotic approaches to prevent and manage disease. Otitis media and sinusitis are two very common infections which are difficult to treat for a number of reasons, including antibiotic resistance. Otitis media (OM) is the most prevalent infectious disease affecting young children, and the major cause of conductive hearing loss among this group. OM is also the leading indication for antibiotic therapy. OM results in 31 million annual visits to physicians' offices and is estimated to have a yearly cost exceeding $5 billion.
Most cases of OM are caused by one of three major pathogens,
Streptococcus pneumoniae
(
S. pneumoniae
) (30-40%), non-typeable
Haemphilus influenzae
(NTHi) (30%) and
Moraxella catarrhalis
(
M. catarrhalis
) (20%). Typically, these infections are treated with antibiotics. In the past three decades, there has been a dramatic worldwide increase in antibiotic resistance in OM pathogens. This has resulted in a reduction of the number of effective antibiotics for this disease and begun to pose a major public health threat. Thus, the use of antibiotics is becoming more complicated as resistance increases, necessitating the testing of microbes before treatment, which can sometimes fatally delay the necessary treatment. In addition, wide antibiotic use is further contributing to the problem of resistance. The need to identify new antibiotics is causing the price of these substances to be so high as to be prohibitive in some cases. Therefore, there is a need for new, innovative, and cost-effective approaches to prevent and manage these diseases. It is believed that the defenses of the eustachian tube and the middle ear (tubotympanum) help to maintain the sterility of the middle ear under normal conditions. To this end, an understanding of the mechanisms that protect the tubotympanum (the middle ear and eustachian tube) from invading organisms and determine the role that they play in the pathogenesis of OM could prove useful in identifying a new treatment.
SUMMARY OF THE INVENTION
A method and an antimicrobial composition for the treatment of ear and sinus infections is disclosed which is effective, reasonably priced, and does not contribute to the problem of antibiotic resistance.
Thus, one embodiment is a pharmaceutical preparation for the treatment of otitis and sinusitis, which has at least one component selected from the group consisting of: lactoferrins, lysozyme, and defensins in an amount effective to reduce the growth of microbes, and a pharmaceutically acceptable carrier. In one embodiment, the defensins are alpha defensins or beta defensins, particularly beta defensin 1 or beta defensin 2 and preferably beta defensin 2. In one embodiment, the dose is from about 0.1 to 100 mg/kg/dose, alternatively from about 0.5 to 50 mg/kg/dose or 0.1 to 1000 mg/kg/day. In one embodiment, the pharmaceutical preparation includes &bgr;-defensin-2, lysozyme, and &bgr;-defensin-1 in an excipient formulated for treatment of and administration to the middle ear.
A further embodiment is a method for the treatment of microbial infections of the ear and sinuses in a mammal, by administering to the mammal a pharmaceutical preparation comprising at least one component selected from the group consisting of lactoferrins, lysozyme, and defensins in an amount effective for the reduction in numbers of the causative infective agents. In one embodiment, the microbial infections of the ear and sinus are otitis media and paranasal sinusitis. In a further embodiment, the administration is orally, intranasally, by aerosolization or into the ear canal. In one embodiment, the beta defensins are beta defensin 1 or beta defensin 2, preferably beta defensin 2. The pharmaceutical may be administered at a dose of about 0.1 to 100 mg/kg/dose, alternatively, 0.5 to 50 mg/kg/dose, 0.1 to 1000 mg/kg/day, or about 0.8 to 800 mg/kg/day. The pharmaceutical composition may be administered 1 to 8 times per day as a pill, a solution, or a suspension. In one embodiment, the pharmaceutical composition includes a salt chelator. In a further embodiment, the pharmaceutical composition includes both lysozyme and lactoferrin. In a further embodiment, the pharmaceutical composition includes both lysozyme and a defensin, preferably &bgr;-defensin-2. In a further embodiment, the pharmaceutical composition includes lysozyme, beta defensin 1 and beta defensin 2. The mammal may be a human, a dog, a cat, a horse, a ferret, a mouse, a rat or a cow.
In a further embodiment, the Otitis media is caused by a microbe selected from the group consisting of NTHi strain 12,
M. catarrhalis, S. pneumoniae
serotype 3, and
S. pneumoniae
serotype 6B.
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Andalibi Ali
Ganz Tomas
Lee Haa-Yung
Li Jian-Dong
Lim David J.
Delacroix-Muirheid C.
House Ear Institute
Knobbe Martens Olson & Bear LLP
Spivack Phyllis G.
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