WO1998057626A1 - Use of l-arginine or a pharmaceutically acceptable salt thereof for production of drugs for treatment of helicobacter pylori infections - Google Patents

Use of l-arginine or a pharmaceutically acceptable salt thereof for production of drugs for treatment of helicobacter pylori infections Download PDF

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Publication number
WO1998057626A1
WO1998057626A1 PCT/SE1997/001101 SE9701101W WO9857626A1 WO 1998057626 A1 WO1998057626 A1 WO 1998057626A1 SE 9701101 W SE9701101 W SE 9701101W WO 9857626 A1 WO9857626 A1 WO 9857626A1
Authority
WO
WIPO (PCT)
Prior art keywords
drug
arginine
helicobacter pylori
pharmaceutically acceptable
treatment
Prior art date
Application number
PCT/SE1997/001101
Other languages
French (fr)
Inventor
Anders Pettersson
Lars Fändriks
Original Assignee
A + Science Invest Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to SE9600791A priority Critical patent/SE9600791L/en
Application filed by A + Science Invest Ab filed Critical A + Science Invest Ab
Priority to AU36367/97A priority patent/AU3636797A/en
Priority to PCT/SE1997/001101 priority patent/WO1998057626A1/en
Publication of WO1998057626A1 publication Critical patent/WO1998057626A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group

Definitions

  • the present invention relates to the use of L- arginine or a pharmaceutically acceptable salt thereof for production of a drug for treatment of infections caused by Helicobacter pylori .
  • Helicobacter pylori is a gram-negative, microaero- philic, curved bacteria, which causes infections in the stomach in humans and some other species, such as pig, monkey, and horse. Approximately 30% of the population in the western countries is affected by Helicoba cter pylori infections. Helicobacter pylori causes a local inflammation, called antrum gastrit, and contributes to other pathological conditions in the gastrodudenal tract. This is mainly related to gastric ulcer, but the infection is also considered as an important factor in the development of atrophic gastritis, stomach cancer and stomach lym- phoma . Eradication of the bacteria also cures the ulcer disease.
  • Medication used for treatment of Helicobacter pylori infections normally consists of antibiotics in combination with bismuth salts and/or antacids, such as hista- mine-2 receptor antagonists or proton pump inhibitors.
  • the effect of this medication is limited due to the fact that it involves a combination of several drugs, resulting in an increase of the side-effects, which leads to a decreased patient compliance, i.e. the patient does not use the drugs in the prescribed way, and high drug costs.
  • Another alternative for treatment of Helicobacter pylori infections is the use of vaccination, either per oral vaccination or parental administered vaccination. Vaccination leads to an activation or a stimulation of the host's immunological defence.
  • Helicobacter pylori infections are chronic infections, the bacteria may develop a certain resistance against this immunological defence, and it is thus difficult to develop an effective vaccine against Heli cobacter pylori .
  • a drug containing L-arginine preferably in the form of a tablet, is effective for eradication of Helicobacter pylori in mammals and other species.
  • the present invention relates to the use of L-arginine or a pharmaceutically acceptable salt thereof for production of a drug for treatment of infections caused by Helicobacter pylori .
  • Fig. 1. shows a graph illustrating the percentage of patients positive for Heli cobacter pylori after treatment with L-arginine and D-arginine, respectively.
  • the present invention relates to the use of L- arginine, at least one of its pharmaceutically acceptable salts or a mixture thereof for production of a drug or a pharmaceutical composition for treatment of infections caused by Helicobacter pylori .
  • the drug may be intended for oral administration, parenteral administration, or rectal administration.
  • the drug may also be intended for delayed release of the ac- tive substance.
  • the active substance may be included in the drug in its neutral form, as a salt or as a pro-drug, which is metabolised by the intended recipient into the active form.
  • the drug may include an inert vehicle and/or other pharmaceutically acceptable additives.
  • the drug according to the invention is suitable for use in combination with other substances affecting Heli cobacter pylori infections, such as antibiotics, hista- mine-2 receptor antagonists, bismuth salts, proton pump inhibitors, ascorbic acid, antacids or sucralfate.
  • substances affecting Heli cobacter pylori infections such as antibiotics, hista- mine-2 receptor antagonists, bismuth salts, proton pump inhibitors, ascorbic acid, antacids or sucralfate.
  • An appropriate dosage is 0.01-30 g L-arginine divided into 1-5 administrations.
  • Example Helicobacter pylori bacteria were detected by the so called urea breath test, UBT .
  • UBT urea breath test
  • This test which is well known to persons skilled in the art, is based on the fact » that Helicobacter pylori bacteria in the stomach metabolise urea into carbon dioxide and water. The carbon dioxide will then be emitted in the breath. If a patient infected with Helicoba cter pylori bacteria drinks a liquid containing isotope labelled urea his breath will then contain isotope labelled carbon dioxide.

Abstract

The present invention relates to the use of L-arginine, at least one of its pharmaceutically acceptable salts or a mixture thereof for production of a drug intended for oral, parenteral, or rectal administration for treatment of infections caused by Helicobacter pylori. The active substance may be included in the drug in its neutral form or as a pro-drug, which is later metabolised by a host into the active form. Furthermore, the drug may include an inert vehicle and/or other pharmaceutically acceptable additives.

Description

USE OF L-ARGININE OR A PHARMACEUTICALLY ACCEPTABLE SALT
THEREOF FOR PRODUCTION OF DRUGS FOR TREATMENT OF HELI-
COBACTER PYLORI INFECTIONS
Field of the invention
The present invention relates to the use of L- arginine or a pharmaceutically acceptable salt thereof for production of a drug for treatment of infections caused by Helicobacter pylori .
Background of the invention
Helicobacter pylori is a gram-negative, microaero- philic, curved bacteria, which causes infections in the stomach in humans and some other species, such as pig, monkey, and horse. Approximately 30% of the population in the western countries is affected by Helicoba cter pylori infections. Helicobacter pylori causes a local inflammation, called antrum gastrit, and contributes to other pathological conditions in the gastrodudenal tract. This is mainly related to gastric ulcer, but the infection is also considered as an important factor in the development of atrophic gastritis, stomach cancer and stomach lym- phoma . Eradication of the bacteria also cures the ulcer disease.
Medication used for treatment of Helicobacter pylori infections normally consists of antibiotics in combination with bismuth salts and/or antacids, such as hista- mine-2 receptor antagonists or proton pump inhibitors. The effect of this medication is limited due to the fact that it involves a combination of several drugs, resulting in an increase of the side-effects, which leads to a decreased patient compliance, i.e. the patient does not use the drugs in the prescribed way, and high drug costs. Another alternative for treatment of Helicobacter pylori infections is the use of vaccination, either per oral vaccination or parental administered vaccination. Vaccination leads to an activation or a stimulation of the host's immunological defence. However, since Helicobacter pylori infections are chronic infections, the bacteria may develop a certain resistance against this immunological defence, and it is thus difficult to develop an effective vaccine against Heli cobacter pylori .
From EP-A-0 689 835 it is known to use a nutrient composition comprising a mixture of 17 different amino acids, including L-arginine, and a fatty acid for the treatment of inflammatory bowel disease. However, since this nutrient composition includes 17 different amino acids, it is relatively complicated to produce.
From JP-A-07267855 it is known to use a glutamine- producing agent containing several amino acids, including L-arginine, e.g. to obtain an antiulcerative effect. Ac- cording to this document it is thus also necessary to use a combination of different amino acids in order to obtain the desired effect.
Summary of the invention It has now surprisingly been found that a drug containing L-arginine, preferably in the form of a tablet, is effective for eradication of Helicobacter pylori in mammals and other species. Thus, the present invention relates to the use of L-arginine or a pharmaceutically acceptable salt thereof for production of a drug for treatment of infections caused by Helicobacter pylori .
The characterising features of the invention will be evident from the following description and the appended claims .
Brief description of the drawing
The invention will now be described in further detail hereinafter with reference to the accompanying drawing on which: Fig. 1. shows a graph illustrating the percentage of patients positive for Heli cobacter pylori after treatment with L-arginine and D-arginine, respectively.
Detailed description of the invention
Thus, the present invention relates to the use of L- arginine, at least one of its pharmaceutically acceptable salts or a mixture thereof for production of a drug or a pharmaceutical composition for treatment of infections caused by Helicobacter pylori .
The drug may be intended for oral administration, parenteral administration, or rectal administration. The drug may also be intended for delayed release of the ac- tive substance.
The active substance may be included in the drug in its neutral form, as a salt or as a pro-drug, which is metabolised by the intended recipient into the active form. Furthermore, the drug may include an inert vehicle and/or other pharmaceutically acceptable additives.
The drug according to the invention is suitable for use in combination with other substances affecting Heli cobacter pylori infections, such as antibiotics, hista- mine-2 receptor antagonists, bismuth salts, proton pump inhibitors, ascorbic acid, antacids or sucralfate.
An appropriate dosage is 0.01-30 g L-arginine divided into 1-5 administrations.
The invention will now be further explained in the following example. This example is only intended to illustrate the invention and should in no way be considered to limit the scope of the invention.
Example Helicobacter pylori bacteria were detected by the so called urea breath test, UBT . This test, which is well known to persons skilled in the art, is based on the fact » that Helicobacter pylori bacteria in the stomach metabolise urea into carbon dioxide and water. The carbon dioxide will then be emitted in the breath. If a patient infected with Helicoba cter pylori bacteria drinks a liquid containing isotope labelled urea his breath will then contain isotope labelled carbon dioxide.
20 patients tested positive for Heli cobacter pylori bacteria with the above mentioned test were used in this example. 10 of these patients were treated with tablets containing L-arginine during 14 days. The dosage used was 1 g given 3 times daily. The remaining 10 patients, constituting a control group, were treated in the same way but with tablets containing D-arginine instead of L- arginine . The presence of Helicobacter pylori bacteria was controlled with the urea breath test 20 and 40 days after day one, i.e. when the first tablet was administered. The result of these tests is shown in figure 1.
It is clearly evident that the treatment with L- arginine was successful in eradication of Helicobacter pylori bacteria.

Claims

1. Use of L-arginine or a pharmaceutically acceptable salt thereof for production of a drug for treatment of Helicobacter pylori infections.
2. Use of L-arginine according to claim 1, charac- terised in that the drug is intended for oral administration.
3. Use of L-arginine according to claim 1, characterised in that the drug is intended for parenteral administration.
4. Use of L-arginine according to claim 1, characterised in that the drug is intended for rectal administration.
5. Use of L-arginine according to any one of claims 1-4, characterised in that the active substance is in- eluded in the drug in its neutral form.
6. Use of L-arginine according to any one of claims 1-4, characterised in that the active substance is included in the drug as a pro-drug, which may be metabolised by a host into the active form.
7. Use of L-arginine according to any one of claims 1-6, characterised in that the drug comprises an inert vehicle.
8. Use of L-arginine according to any one of claims 1-7, characterised in that the drug is suitable for use in combination with other substances affecting Heli cobacter pylori infections, such as antibiotics, hista- mine-2 receptor antagonists, bismuth salts, proton pump inhibitors, ascorbic acid, antacids or sucralfate.
PCT/SE1997/001101 1996-02-27 1997-06-19 Use of l-arginine or a pharmaceutically acceptable salt thereof for production of drugs for treatment of helicobacter pylori infections WO1998057626A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
SE9600791A SE9600791L (en) 1996-02-27 1996-02-27 Method for eradication of Helicobacter pylori infection
AU36367/97A AU3636797A (en) 1996-02-27 1997-06-19 Use of l-arginine or a pharmaceutically acceptable salt thereof for production of drugs for treatment of (helicobacter pylori) infections
PCT/SE1997/001101 WO1998057626A1 (en) 1996-02-27 1997-06-19 Use of l-arginine or a pharmaceutically acceptable salt thereof for production of drugs for treatment of helicobacter pylori infections

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9600791A SE9600791L (en) 1996-02-27 1996-02-27 Method for eradication of Helicobacter pylori infection
PCT/SE1997/001101 WO1998057626A1 (en) 1996-02-27 1997-06-19 Use of l-arginine or a pharmaceutically acceptable salt thereof for production of drugs for treatment of helicobacter pylori infections

Publications (1)

Publication Number Publication Date
WO1998057626A1 true WO1998057626A1 (en) 1998-12-23

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Country Status (3)

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AU (1) AU3636797A (en)
SE (1) SE9600791L (en)
WO (1) WO1998057626A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6552047B2 (en) 1998-11-17 2003-04-22 Nitromed, Inc. H2 receptor antagonist compounds in combination with nitric oxide donors, compositions and methods of use
US6852739B1 (en) 1999-02-26 2005-02-08 Nitromed Inc. Methods using proton pump inhibitors and nitric oxide donors
US7211590B2 (en) 2002-08-01 2007-05-01 Nitromed, Inc. Nitrosated proton pump inhibitors, compositions and methods of use
US8337917B2 (en) 1999-03-12 2012-12-25 Mars, Incorporated Nut skin products

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07267855A (en) * 1994-03-30 1995-10-17 Taiho Yakuhin Kogyo Kk Glutamine producing agent
EP0689835A2 (en) * 1994-06-30 1996-01-03 Ajinomoto Co., Inc. Composition comprising a mixture of amino acids and at least one N-3 fatty acid

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07267855A (en) * 1994-03-30 1995-10-17 Taiho Yakuhin Kogyo Kk Glutamine producing agent
EP0689835A2 (en) * 1994-06-30 1996-01-03 Ajinomoto Co., Inc. Composition comprising a mixture of amino acids and at least one N-3 fatty acid

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
APPLIED AND ENVIRONMENTAL MICROBIOL., Volume 60, No. 9, 1994, P. NEDENSKOV, "Nutritional Requirements for Growth of Helicobacter Pylori", pages 3450-3453. *
CANCER LETT., Volume 102, 1996, K.B. SHAPIRO et al., "Induction of Nitric Oxide Synthesis in Murine Macrophages by Helicobacter Pylori", pages 49-56. *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6552047B2 (en) 1998-11-17 2003-04-22 Nitromed, Inc. H2 receptor antagonist compounds in combination with nitric oxide donors, compositions and methods of use
US6936627B2 (en) 1998-11-17 2005-08-30 Nitromed, Inc. Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use
US7129251B2 (en) 1998-11-17 2006-10-31 Nitromed, Inc. Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use
US7256205B2 (en) 1998-11-17 2007-08-14 Nitromed, Inc. Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use
US6852739B1 (en) 1999-02-26 2005-02-08 Nitromed Inc. Methods using proton pump inhibitors and nitric oxide donors
US7332505B2 (en) 1999-02-26 2008-02-19 Nitromed, Inc. Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use
US8337917B2 (en) 1999-03-12 2012-12-25 Mars, Incorporated Nut skin products
US8357405B2 (en) 1999-03-12 2013-01-22 Mars, Incorporated Nut skin products and methods of use thereof
US7211590B2 (en) 2002-08-01 2007-05-01 Nitromed, Inc. Nitrosated proton pump inhibitors, compositions and methods of use

Also Published As

Publication number Publication date
AU3636797A (en) 1999-01-04
SE9600791L (en) 1997-08-28
SE9600791D0 (en) 1996-02-27

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