Chelate compound for treating Helicobacter pylori infections

Abstract: An antibacterial agent is provided, which has an action for inhibiting growth of Helicobacter pylori participating to occurrence of chronic gastritis and gastric ulcer, and a highly safe substance is used as an effective component therein. An antibacterial agent for Helicobacter pylori is characterized in that at least one substance selected from the group consisting of ethylenediaminetetraacetic acid and its metal salts is contained as an effective component.

Description: FIELD OF THE INVENTION The present invention relates to the use of an antibacterial agent for Helicobacter pylori , in more detail, to an antibacterial agent for Helicobacter pylori , said agent contains as an effective component a chelate compound, safety of which against human bodies is confirmed. BACKGROUND OF THE INVENTION Recently, it has been found that Helicobacter pylori is much participated to occurrence of chronic gastritis and gastric ulcer. In Japan, it is said that about 60 millions people corresponding to an about half of the total population are infected with Helicobacter pylori (Shokunokagaku, Vol. 265, pages 87-99, 2000). Cure of chronic gastritis and gastric ulcer can be attained by removing the bacterium from stomach by means of administration of antibiotics etc. However, there are some cases wherein the bacterium is hard to be removed depending on patients. Further, as to antibiotics, there are some problems concerning appearance of resistant bacteria and side effects. Further, it is desirable to remove the bacterium not only on people being attacked with a disease but also on people infected with a disease, but it is economically difficult because the number of objectives is quite large. Therefore, an antibacterial agent for Helicobacter pylori which is highly safe and which can be taken easily is required. Ethylenediaminetetraacetic acid (hereinafter, sometimes abbreviated to EDTA) has a chelating action on various metal ions and it is known as a reaction inhibitor of enzymes requiring metal ions. Further, EDTA and its metal salts are approved as a food additive in many countries since they have a stabilizing effect for food colors. Thus, evaluation for safety of EDTA etc. has been already established and an acceptable daily intake (ADI) as a food additive is 2.5 mg/kg of weight (FAO/WHO: Codex Alimentarius Commission, List of additives evaluated for their safety in use in food. CAC/FAL 1-1973, 1973). Further, in the U.S.A., it is approved that EDTA disodium salt is added to foods within a concentration range of 36-500 ppm (Code of Federal Regulations, Title 21: Food and Drugs, US Government Printing Office, 1988). A composition for the treatment of gastritis, gastroduodenitis and gastroduodenal ulcers containing disodium ethylenediaminetetraacetic acid is described in RO-A-65968. The treatment of Helicobacter pylori infections with ethylenediaminetetraacetic acid is described in WO 96/00569. A further composition containing Fe (III) ethylenediaminetetraacetic acid is described in US -A-5,356,832 for the control of intraocular pressure. SUMMARY OF THE INVENTION An object of the invention is to provide the use of an antibacterial agent which has an action for growth inhibition of Helicobacter pylori which participates to occurrence of chronic gastritis and gastric ulcer and in which a highly safe substance is used as an effective component. The inventors of the present invention have searched for antibacterial substances for Helicobacter pylori among of substances accepted as food additives in order to solve the above-mentioned problem, and found that one particular metal salt of EDTA has an action for growth inhibition of Helicobacter pylori . Thus, the present invention has been completed based on this finding. That is, the present invention relates to the use of an antibacterial agent in the manufacture of a medicament for Helicobacter pylori , characterized in that iron (III) sodium ethylenediaminetetraacetic is contained as an effective component. BRIEF DESCRIPTION OF THE DRAWINGS In the accompanying drawings: Fig. 1 is a drawing showing growth rates of Helicobacter pylori in the presence of disodium ethylenediaminetetraacetate having various concentrations; and Fig. 2 is a drawing showing growth rates of Helicobacter pylori in the presence of iron (III)-sodium ethylenediaminetetraacetate having various concentrations. DETAILED DESCRIPTION OF THE INVENTION According to the invention, von (III) sodium EDTA is used as an effective component of an antibacterial agent for Helicobacter pylori . The antibacterial agent according to the invention may be adopted to various forms. For example, if necessary with any suitable adj uvant (such as a vehicle, an extender and a sweetening agent), to make any type of an agent such as a powder, a granule, a solution and a capsule. Further, it may be used by adding them to various foods. The antibacterial agent according to the invention is generally administered orally. Dosages may be determined in due consideration of ADI of EDTA, that is, 2.5 mg/kg of weight, as well as these effective amounts for growth inhibition of Helicobacter pylori and a stomach volume (about 1.5 L) of human beings. In order to inhibit growth of Helicobacter pylori in stomach, iron (III) sodium EDTA may be administered for an adult per a day at about 10-500 mg, preferably 10-150 mg, calculated as free EDTA. Also, it is suitable to administer for an adult per a day at about 60-300 mg, preferably 60-150 mg. If administered in excess, there may be occurred a side effect. Herein, the administration may be carried out at a time or may be divided in several times. The antibacterial agent of the inventionmaybe used in together with other known antibacterial agents for Helicobacter pylori , or also with proton pump inhibitors such as omeprazole or anti-ulcer agents such as bismuth salt. According to the invention, the use of an antibacterial agent for the manufacture of a medicament for Helicobacter pylori is provided in which a particular salt of the highly safe EDTA approved as a food additive in many countries is contained an effective component. Growth of Helicobacter pylori present in a digestive system of human beings can be inhibited effectively by administering the antibacterial agent alone or in together with suitable adjuvants or by taking a food containing it. Thus, according to the invention, gastrointestinal disorders reported to be participated to Helicobacter pylori can be prevented and treated effectively. EXAMPLES The invention is illustrated as follows with showing the Example, but the invention is not limited thereto. Example 1 Helicobacter pylori (ATCC 43504 strain, purchased from . American Type Culture Collection) was cultured with use of a 96-well plate. That is, each 0.1 mL of a medium having a composition of 3% tryptic soy broth (made by Difco), 10% calf serum for tissue culture (made by Wako Pure Chemical) and disodium ethylenediaminetetraacetate (made by Wako Pure Chemical) or iron (III)-sodium ethylenediaminetetraacetate (made by Dojin Molecular Technologies) having various concentrations adjusted to pH 8.0 was poured separately into a 96-well plate. After inoculation of Helicobacter pylori , the plate was introduced in a sealed vessel of 2.5 liter volume, into which AnaeroPack-Helico (made by Mitsubishi Gas Chemical), an agent for absorbing oxygen and generating carbon dioxide gas, was also introduced, and cultured for 5 days under an anaerobic condition at 37°C. Growth of Helicobacter pylori was determined by means of a 96-well plate reader with use of a 540 nm or 595 nm filter. Herein, as a control for absorbance determination, a medium without EDTA was used. Results thereof are shown in Fig. 1 and Fig. 2. In the figures, degree of the growth of Helicobacter pylori depending on concentration of the effective component like EDTA etc. was measured with turbidity, and is shown with the rate against turbidity in growth of Helicobacter pylori in the control medium. From Fig. 1, it is seen that growth of Helicobacter pylori ATCC 43504 strain is inhibited by means of 0.025-1 mM disodium ethylenediaminetetraacetate. Further, from Fig. 2, it is seen that growth of Helicobacter pylori ATCC 43504 strain is inhibited by means of 0.1-0.5 mM iron (III)-sodium ethylenediaminetetraacetate. Herein, 0.025-1 mM disodium ethylenediaminetetraacetate (molecular weight: 372Da) is converted into 9.3-372 mg/L, which is less than 500 ppm, which is, as described above, upper limit of the concentration approved for food additives in the U.S.A. Further, since a stomach volume of human being is said as about 1.5 L, growth of Helicobacter pylori can be inhibited if 14-558 mg (11-438 mg as free EDTA) of disodium ethylenediaminetetraacetate is taken. On the other hand, for the case of iron (III)-sodium ethylenediaminetetraacetate (molecular weight: 421Da) according to the invention, growth of Helicobacter pylori can be inhibited if 63-316 mg is taken.

Claims: Use of an antibacterial agent comprising iron (III) sodium ethylenediaminetetraacetate for the manufacture of a medicament for growth inhibition of Helicobacter pylori. Use of claim 1 wherein the iron (III) sodium ethylenediaminetetraacetate is present in an amount of 0.1 to 0.5 mM.

Inventors: NAGAI TOSHIRO, OITA SHIGERU, NAGAI, TOSHIRO, OITA, SHIGERU
Applicants: INC ADMIN AGENCY NARO, NAT INST OF AGROBIO SCIENCES, INCORPORATED ADMINISTRATIVE AGENCY NATIONAL AGRICULTURE AND BIO-ORIENTED RESEARCH ORGANIZATION, NATIONAL INSTITUTE OF AGROBIOLOGICAL SCIENCES
Application year: 2001
Main classification: A61K31
IPC codes: A61K31, A61P1, A61P31