ES2754881A1 - Procedure for the treatment of Plasmodium infections resistant to drugs and the product used (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

Procedure for the treatment of Plasmodium infections resistant to drugs and the product used. The invention relates to the use of a gas produced by reactive ionic salts as an active ingredient in the treatment of drug resistant Plasmodium infections. More specifically, said active ingredient is chlorine dioxide dissolved in water, including sodium chlorite (NaClO2) as a precursor or excipient, whether it is activated through stomach acids or other acids, to achieve the formation of chlorine dioxide as an active principle, obtaining a product that does not generate its own toxic waste by decomposing into salt and oxygen. (Machine-translation by Google Translate, not legally binding)

Description

D E S C R I P C I Ó N

PROCEDURE FOR THE TREATMENT OF PLASMODIUM INFECTIONS

RESISTANT TO MEDICINES AND PRODUCT USED

OBJECT OF THE INVENTION

The present invention relates to a method that has been specially designed to carry out the treatment of drug-resistant plasmodium infections.

The invention also affects the active principle used in the process.

The object of the invention is, in addition to providing a highly effective procedure in the treatment of the aforementioned infections, the product used as a drug does not generate its own toxic residues when decomposing into salt and oxygen.

BACKGROUND OF THE INVENTION

Malaria affects more than 200 million people, and more than one million deaths a year are associated with malaria on the African continent alone.

In endemic areas, the presence of infections is found, especially in the vicinity of wetlands.

Malaria is known as the infection of the parasite of the genus Plasmodium. The difference in medical literature includes at least four species, P. vivax, P. falciparum, P. malariae and P. ovale, in the case of infections that concern humans.

Malaria is commonly transmitted to humans by the bite of Anopheles-type mosquitoes. After the mosquito bite, the parasite manages to invade liver cells where it multiplies and then manages to invade the red blood cells.

After an incubation period of 8 to 14 days, symptoms consisting of chills, fever, muscle aches, headache, anemia and an enlarged spleen will be seen. This incubation period can last for many weeks depending on the type and conditions, being quite insidious. Affected red blood cells are destroyed by infection.

Classical pharmacology uses quinine, chloroquine, primaquine, or amodiaquine, as the main methods to combat this parasitic infection. However, over time it has been discovered that Plasmodium strains resistant to the drugs used so far have been developed and, in some cases, the strains turn out to be resistant to many or all current therapeutic agents, since resistance to These new agents are also developing rapidly.

DESCRIPTION OF THE INVENTION

The present invention consists of a novel method to treat a Plasmodium infection, whether it is resistant to antimalarial drugs or not through a gas dissolved in water as the main active agent, where through the mechanism of action as an oxidant, no one can create resistors.

More specifically, it has been found that acidified sodium chlorite gas (NaClO2), which is a pharmaceutically acceptable salt of pH 13, when administered in conjunction with water, is useful in the treatment of individuals suffering from Plasmodium infections. , whether they are resistant to known drugs or not.

Experimentally, it has been found that administering amounts of these acidified salts are pharmaceutically acceptable, since the chlorine dioxide gas that is the active ingredient thereof, is excellently diluted in the water without hydrolyzing as would be the case with hypochlorite. It has been observed in treatments with volunteers that a concentration of 150 to 400 mg / ml of chlorine dioxide dissolved in 500 ml of water and applied orally three to six times a day within a few hours, is an effective method of treating a drug-resistant plasmodium infection.

DETAILED DESCRIPTION OF THE INVENTION

Chlorine dioxide, the compound of this invention, is well known for decontamination and cleaning of waters and also as an antiseptic. However, it does not form part of being included in the state of the art in what refers to a pharmaceutical product, since it has not been listed as an active ingredient in any official pharmaceutical list until now.

Chlorine dioxide is widely available due to its industrial use and can be easily prepared by those of ordinary skill in the art of disinfectant preparation.

When the compound is selected for co-administration with chloroquine for the prophylaxis of drug-resistant malaria, the efficacy of chlorine dioxide in treatment has been observed.

The compound of this invention is useful both in the form of base salts and in the form of activated gas achieved through the addition of an acid and dissolved in water. Sodium chlorite salts are simply a more convenient form of transportation and use and, in practice, are the basic salt substance for the manufacture and use of the chlorine dioxide solution. The term "pharmaceutically acceptable reactive ionic salts" applies to any addition of non-toxic organic or inorganic acid from the base compounds to the salt.

The most important use contemplated for the present invention is its use in the treatment of Plasmodium infections by species such as vivax, malariae, ovale and falciparum, but also malaria infections of P. falciparum strains that become resistant to drugs in humans. . The term "drug resistant malaria" means a malarial infection, particularly malaria resulting from P. falciparum infection. in humans, it is substantially unresponsive to treatment or prophylaxis with existing therapeutic and prophylactic agents such as quinine, chloroquine, amodiaquine, primaquine, or others.

Antimalarial agents used in the combination therapy or prophylaxis of this invention include any therapeutic or prophylactic agent used in the treatment or prophylaxis of malaria infections, whether or not drug resistant.

The preferred route of administration is oral administration. For oral administration, the compound can be formulated into liquid preparations such as capsules, pills, tablets, troches, lozenges, melts, powders, solutions, suspensions, or emulsions. The solid unit dosage forms may be a capsule which may be of the ordinary hard or soft shell gelatin type containing, for example, bicarbonate, glucose, fructose, galactose or maltose, and inert fillers such as lactose, sucrose, fructose, galactose or maltose, and cornstarch. Suitable excipients for use in oral liquid dosage forms include diluents such as water or other pharmaceutically acceptable emulsifiers such as petrolatum, glycerin, carbomers, or other pharmaceutical emulsifying agents or adjuvants. The use of oils that can be used in the parenteral formulations of this invention is included, such as those of petroleum, animal, vegetable or synthetic origin; for example, peanut oil, soybean oil, sesame oil, cottonseed oil, corn oil, olive oil, petrolatum, glycerin, and mineral oil.

The parenteral compositions of this invention will typically contain from about 0.05% to 1.5% by weight of the active ingredient in solution. Preservatives and buffers can also be used advantageously. In order to minimize or eliminate irritation at the site of infection, such compositions may contain a nonionic surfactant. The amount of surfactant in such formulations ranges from about 3 to 15% by weight.

Pharmaceutical chlorine dioxide compositions are widely available and can be used in the practice of this invention. Commonly available dosage forms contain 25 to 250 mg and should be administered to a human patient 1 to 3 or 4 to 8 times daily, as required. Such dosage forms and frequency of Administration are suitable for use in practicing the method of this invention. Pharmaceutical compositions of antimalarial agents such as chloroquine are also widely available and can be used additionally if necessary in practicing the method of this invention. Combination dosage forms are also specifically contemplated for use in the methods of this invention.

The biological mode of action is based on the sensitivity of Plasmodium to all oxidative processes. Chlorine dioxide is pH selective and releases a large amount of molecular oxygen as it dissociates in the blood. It is calculated that for each milliliter of chlorine dioxide, approximately 433 million oxygen molecules are released for each red blood cell.

It is well known that the different variations of Plasmodium are sensitive to oxygen, which makes it difficult to investigate them in vivo in the laboratory and in common Petri dishes in tests. However, it is this same fact that allows the effectiveness of the treatment when the red cells infected by the Plasmodium parasite are oxidized by their acidic pH.

Since chlorine dioxide contains two oxidizing components, both on the part of oxygen and on the part of chlorine, the parasite is quickly and forcefully oxidized and rendered useless.

This way of acting without poisoning makes resistance by Plasmodium impossible, since chlorine dioxide has been used in the industry for 100 years without causing any resistance due to its mechanism of action.

Unlike other oxidants, chlorine dioxide is pH selective and mainly attacks cells with higher acidity, such as cells affected by the parasite loaded with acidic metabolic residues of the parasite.

At the same time, they oxidize thiols and phenols present in the body, which represent an essential basis for the proliferation of falciparum.

In particular, the compounds of the present invention can be effective for:

■ Malaria

■ P. falciparum

■ P. vivax

■ P. berghei

■ P. brasilianum

■ Toxoplasmosis

■ T. gondii

■ Trypanosomiasis

■ Gambian TB

■ Rhodesian TB

■ TB brucei

■ TB congleuse

■ Live TB

■ T. cruzi

■ T. musculi

■ L. major

■ L. braziliensis

■ L. donovani

■ Amebiasis

■ Primary amoebic meningitis

■ Chronic acanthamoeba encephalitis and encephalitis

■ A. culbertsoni

■ Giardiasis

■ G. intestinalis

■ Babesiosis

■ B. bovis

■ B. bigemina

EXAMPLE OF PRACTICAL REALIZATION OF THE INVENTION

The following example is intended to illustrate, but not in any way limit the compositions useful in the methods of this invention.

In a group of 3 volunteers affected by malaria in Madagascar, a remission of 100% could be observed after 2 days of treatment.

A 9-year-old girl was admitted with a fever of 41 ° C about to convulse, after giving her a dosage of 100 milligrams, a complete remission of the symptoms was observed after 5 hours. The next day, the girl was completely normal and was able to play with other children her age.

The other two people, a man and a woman, received a high dose of 450 milligrams for 2 days and a complete remission was observed in both the biochemical and microscopic tests.

In this sense, the preparations were obtained in the usual way, while the tests indicated the remission of the Parasites the following day.

Claims (8)

1a.- Procedure for the treatment of Plasmodium infections, characterized in that it consists of the treatment of the infection through chlorine dioxide dissolved in water as the main active agent. 2a.- Procedure for the treatment of Plasmodium infections, according to claim 1, characterized in that the treatment is carried out orally. 3rd .. Procedure for the treatment of Plasmodium infections, according to claim 1, characterized in that the treatment is carried out rectally. 4a.- Procedure for the treatment of Plasmodium infections, according to claim 1, characterized in that the treatment is carried out parenterally. 5a.- Procedure for the treatment of Plasmodium infections, according to claim 4a, characterized in that in the case of treating parenterally, the active ingredient participates between 0.05% and 1.5% of the active ingredient in solution. 6a.- Procedure for the treatment of Plasmodium infections, according to claims ia and 2a, characterized in that sodium chlorite (NaClO2) is used to obtain chlorine dioxide, which is activated through stomach acids or through other acids. 7a.- Product for the treatment of Plasmodium infections, characterized in that it consists of a medicine in which sodium chlorite (NaClO2) participates as the main excipient. 8a.- Product for the treatment of Plasmodium infections, according to claim 6a, characterized in that the galenic form is an aqueous form, preferably a solution or suspension.