Inhibitor of helicobacter pylori colonization

Details Inhibitor of helicobacter pylori colonization Inhibitor of helicobacter pylori colonization

1999-12-10

2001-05-22

Reamer, James H. (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C514S007600, C514S008100, C514S055000, C514S056000, C514S024000, C536S002000, C536S004100, C536S123000, C536S123100

Reexamination Certificate

active

06235709

ABSTRACT:

TECHNICAL FIELD
The present invention relates to an inhibitor of the colonization of
Helicobacter pylori
(hereinafter referred to as
H. pylori
or Hp) which is associated with the occurrence of peptic ulcers, which inhibitor is capable of eliminating
H. pylori
from the stomach, and a food containing the inhibitor, especially an anti
H. pylori
functional food.
BACKGROUND OF THE INVENTION
At present it is believed that eradication of
H. pylori
from the stomach is essential for treating peptic ulcers fully. The combination of an antibiotic and an inhibitor of gastric acid secretion has been generally proposed as a therapy for eradication of
H. pylori
as described below.
H. pylori
is a gram-negative spiral rod-shaped bacterium having some flagella at one end and inhabiting the human gastric mucosa. Marshall, B. J. and Warren, J. R. in Australia reported in 1983 that this bacterium was frequently detected in stomach biopsy specimens from patients with gastric ulcers. At that time this bacterium was named
Campylobacter pylori
since it resembles Campylobacter in morphology and growth characteristics. Later, it was found that the bacterium is different from Campylobacter in the fatty acid composition of its outer membrane and sequence of ribosome 16S-RNA. Therefore, the bacterium is now referred to as
Helicobacter pylori
and belongs to the newly established genus of Helicobacter.
Since then, many reports have been published based on epidemiological studies, indicating that this bacterium causes gastritis, gastric ulcers, and duodenal ulcers and is associated with diseases such as gastric cancer. Once Hp colonizes gastric mucosa, it cannot be eradicated in the stomach and continues to inhabit the stomach, although the immune response to infection thereof is strong, i.e., the antibody titer is high. Therefore, unless Hp is completely eliminated from the stomach by antibiotic therapy, the infection will return to the same level as before treatment within about a month after the administration of antibiotics is stopped. Additionally, the pH of the stomach is maintained very low by HCl, which is a strong acid, and therefore most antibiotics are apt to be inactivated. For this reason, the combination of an antibiotic and a proton pump inhibitor which strongly suppresses the secretion of gastric acid is utilized often in a greater dose than usual for eradication of
H. pylori.
Recently, a new treatment employing a combination of bismuth subsalicylate, metronidazole, and tetracycline has proved to have the highest rate of elimination of Hp, but metronidazole in the combination is known to cause the rapid emergence of an antibiotic-resistant strain when used alone. In developing countries, this medicine has been used widely for treating diarrhea patients, and as a result there is a high rate of infection with metronidazole-resistant Hp.
Thus, the administration of antibiotics for a long time has the serious problems of increasing antibiotic-resistant strains as well as causing side effects.
At present, an immunological therapy approach using an oral vaccine has been proposed in order to solve problems such as side effects and increase of antibiotic-resistant strains by treatment with antibiotics for the eradication of the bacteria. For this purpose it is essential to develop model animals for Hp infection. However, Hp cannot easily infect small animals such as mice or rats, and germ-free animals are required for infection. Also, fresh isolates are required for maintaining infection for a long time. These requirements have obstructed studies aimed at developing new methods for prevention and treatment. Also, the oral vaccine preparation usually has heat-labile toxin (LT) derived from
E. coli
and cholera toxin, and mucosal immunity cannot be attained without these adjuvants. In respect to safety in practical application, LT from
E. coli
and cholera toxin have a high level of toxicity, and the oral vaccine method has unsolved problems in its practical application to humans. Furthermore, the vaccine is predominantly used for prevention, and therefore it has no effect on patients who have already been infected with Hp.
As a new attempt to inhibit Hp, the use of specific antibodies is proposed, which antibodies are obtained from the eggs of hens immunized against Hp whole cells as an antigen. However, complete elimination of Hp from the stomach using antibodies against whole cells of Hp cannot be expected. Also, the actual effect on elimination of Hp from the stomach has not been confirmed.
On the other hand, it is disclosed that cells of certain bifid bacteria or lactic acid bacteria, and polysaccharides extracted from these cells are useful in prevention or treatment of gastric ulcers (Japanese Patent Application Kokai No. 4-5236), and that polysaccharide of rhamnose, ramnan, derived from certain seaweed and oligosaccharide of rhamnose are useful as an antiulcer (Japanese Patent Application Kokai No. 6-247861).
Japanese Patent Application Kokai No. 7-138166 describes the use of fucoidan, which is a polysaccharide derived from Nemacystus. This publication states that fucoidan inhibits the colonization of Hp in gastric mucosa and has antiulcer activity. However, ulcers induced with acetic acid, which are basically different from Hp-induced ulcers with respect to pathological development, are used in order to show the effects of treatment of ulcers in that publication. Therefore, in that publication, there is no evidence for suppressing the formation of ulcers caused by Hp infection. Furthermore, that publication states that fucose (monosaccharide) is considered to be a colonization factor (adhesin), and an in vitro experiment based on that assumption was performed using biotinylated fucose as an adhesion marker to see an inhibitory effect of fucoidan on Hp colonization. However, fucose is not considered to be an adhesin at present, so that experiment does not show an inhibitory effect of fucoidan on Hp colonization.
As explained above, the long-term use of antibiotics for elimination of Hp results in an increase in antibiotic-resistant bacteria as well as side effects, and a vaccine has not been developed for practical use. Also, attempts to use egg antibodies against Hp whole cells cannot eradicate Hp, and therefore are not effective for prevention or treatment; of gastritis, gastric ulcers, and duodenal ulcers.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an effective and safe inhibitor of Hp colonization which is associated with the occurrence of peptic ulcers, which inhibitor is capable of inhibiting the colonization of Hp effectively without the disadvantages of side effects and increase of drug-resistant strains which are associated with the use of antibiotics, and to provide a food for treating or preventing peptic ulcers, including a physiologically functional food and a food for medical use.
Other objects and advantages as well as the nature of the present invention will be apparent from the following description.
Generally, the first step for completion of an infection of a bacterium is adhesion of the bacterium to a host cell and colonization of the bacterium by growing there. For the bacterium to adhere to the host cell, an adhesin has to bind to a receptor on the surface of the host cell. The specificity of the infective site of the bacterium is determined by this adhesin and the receptor. If the receptor molecule coexists when the bacterium adheres to the host cell, competitive inhibition occurs and an infection does not occur.
An adhesin of Hp and a receptor on human gastric mucosa are supposed to be target molecules for inhibition of Hp infection. The present inventors clarified by studies regarding the mechanism of adhesion of Hp that the adhesin of Hp, which had not been elucidated, is urease produced by Hp. Furthermore, the present inventors demonstrated that the oral administration of antibodies obtained from chicken eggs against urease of Hp can remarkably suppress the growth of Hp in the stomach (Japanese Patent Application

Affiliated with

Also associated with

Rating

Inhibitor of helicobacter pylori colonization does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inhibitor of helicobacter pylori colonization, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibitor of helicobacter pylori colonization will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2508870