Method of inhibiting formation of infectious microorganisms

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – C-o-group doai

Reexamination Certificate

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Reexamination Certificate

active

06355692

ABSTRACT:

BACKGROUND
The present invention relates to methods of inhibiting replication of three pathogenic microorganisms, pseudorabies virus,
Neisseria gonorrheae
, and
Neisseria meningiditis.
Pseudorabies virus, a member of the Herpesvirus family, primarily affects swine.
Because virus is present in the nasal and oral discharges of infected pigs, infection is usually transmitted between pigs by none to nose contact. Contaminated drinking water and feed buckets may also transmit disease. Clinical symptoms in pigs can vary from undetectable to death. The extent of the symptoms depends on the age and immune status of the animal at the time of infection, the virus dose, route of infection, and strain of virus. Young pigs may be severely affected with a 100% mortality in pigs under 2 weeks of age. Piglets may die suddenly or, prior to death, exhibit symptoms which include fever, loss of appetite, convulsions, and paddling. The severity of clinical signs decreases with age, and older pigs may only experience fever and inappetence of a few days duration.
Since pseudorabies is a virus infection, antibiotics have no effect. The primary methods for preventing spread of the disease involves treatment of environmental surfaces with agents that inactivate the virus. Examples of such agents are phenolic compounds, quaternary ammonium compounds, chlorhexidine diacetate, iodines, and 5% sodium hydroxide. Vaccines may also be used to control spread of the disease. Additional methods for inhibiting replication of the virus, and thereby controlling the spread of the virus and the severity of the disease in swine exposed to the virus are desirable.
Neisseria gonorrhea
is a gram negative bacterium that is pathogenic in humans. The bacterium is spread from person to person by contact with infected secretions, most often by sexual contact. Once the pathogen is deposited on a mucosal surface, a complex series of molecular interactions occur that result in invasion of mucosal columnar cells. The spectrum of diseases ranges from local infections of the urethral, cervical, rectal and oropharyngeal membranes to invasion of the pelvis or epididymis, to invasion of the blood stream, with or without dissemination to distant organs such as heart valves, joints, and pericardium. The pathogen may also infect the conjunctiva. Gonococcal conjunctivitis is most often contracted by neonates passing through an infected birth canal, although adults can also be infected.
The quest for a gonococcal vaccine has been ongoing for many years with virtually no success. Accordingly, the primary treatment involves preexposure or postexposure antibiotic prophylaxis. In addition to antibiotic eyedrops, silver nitrate has also been used to treat neonatal gonococcal conjunctivitis. Unfortunately, the bacterium has developed resistance to some of the most common antibiotics, such as penicillin. Accordingly, additional compositions for reducing growth of this pathogen is desirable.
Neisseria meningiditis
, another member of the genus Neisseria, is also pathogenic in humans. The organism is carried on the nasopharyngeal mucosa of infected individuals and, presumably, is transmitted from person to person through passage of respiratory secretions or aeosolized droplets. Although the organism may cause oropharyngitis, it is primarily a saprophyte that asymptomatically colonizes the majority of human beings sometime during their lives. As with other neisserial species, it can sometimes colonize the genital tract or conjunctiva. On rare occasions, the organism invades the blood stream. Once the organism has invaded the blood stream, an overlapping array of clinical outcomes ranging from a transient bacteremia, to invasion of the meninges, and encephalitis can occur. Treatment primarily involves administration of antibiotics. Vaccines are also used to prevent infection. Unfortunately, the bacterium may develop resistance to the antibiotics. Moreover, the duration of immunity with the currently available vaccines is limited. Accordingly, it is desirable to have new methods for preventing or inhibiting growth of
Neisseria meningiditis.
SUMMARY OF THE INVENTION
The present invention provides a new method of inhibiting the formation of infectious pseudorabies virus particles, in a host cell. The method involves administering a poly-hydroxylated stilbene, particularly resveratrol, or a derivative thereof to a pseudorabies virus infected host cell. The poly-hydroxylated stilbene is administered to the host cell in an amount sufficient to inhibit replication of the virus in the virus-infected host cell. Such method is useful for preventing the spread of pseudorabies virus from a virus- infected host cell to a non-infected host cell. Such method is also useful for establishing a model system for studying the molecular events that occur during replication of pseudorabies virus. In vivo, the method involves administering a composition comprising a poly-hydroxylated stilbene, preferably a tri-hydroxylated stilbene, or a derivative thereof to a non-human animal prior to or shortly after exposure of the animal to the virus. Such method is useful for reducing the cytopathic effect of a pseudorabies virus infection.
The present invention also provides a method of inhibiting replication of the gram negative bacteria belonging to the genus Neisseria, particularly
Neisseria gonorrhea
and
Neisseria meningiditis
. Such method involves contacting the bacterium with a composition containing a tri-hydroxylated stilbene or derivative thereof. In vivo, such method can be used to treat an individual who has come in contact with, e.g., a carrier, or an individual who is expected to come into contact with the bacterium, i.e., an individual who may be exposed to the carrier. In vivo, such method comprises administering a composition comprising a therapeutically effective amount of a tri-hydroxylated stilbene, particularly resveratrol, or a derivative thereof to said subject.


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