G. M. Golzar Hossain, Lecturer, Department of Chemistry, University of Dhaka, Dhaka-1000, Bangladesh.
The following specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed.
The invention concerns medication for arsenic toxicity in human body from a thiol compound name DMSA, meso-2,3-dimercaptosuccinic acid.
DMSA combines in the body with arsenic, which inhibit pyruvate oxidase system competing for the sulphydryl groups in proteins. These have a greater affinity than the proteins for arsenic and resulting compounds are stable and rapidly excreted by the kidneys. DMSA would be used in the treatment of acute poisoning by arsenic.
DMSA is a dithiol (containing two sulphydryl or S-H groups), a lipid-soluble compound, has a large therapeutic window and is the least toxic of the dithiol compounds. Meso-2,3-dimercaptosuccinic acid is a water-soluble, non-toxic, orally administered metal chelating agent which possesses the potential to function as an antioxidant by removing arsenic from the site of deleterious oxidation reactions and can be used as an antidote to arsenic toxicity.
Removal of Arsenic from the body
Arsenic (As) combines with thiol group of protein present in the human body to form a complex of arsenic-protein (Complex-1).
DMSA has the ability to make free the affected protein by removing arsenic from the complex-1 in the human body according to the following reaction:
The principal object of this invention is to produce a medicine for arsenic toxicity in human body.
Another object of this invention is to remove the arsenic from the human body of the affected people caused by arsenic.
According to the present invention the medication for arsenic toxicity in human body which comprises the steps of grinding and mixing the raw materials at the required proportion and put these into the capsule as a desired measurement of DMSA to obtain the required medicine.
Patients exposed to arsenic will frequently have a garlic smell to their breath and to tissue fluids. In trivalent arsenic poisoning the clinical effects depend on the chronicity of the exposure. Acute exposures generally present with gastrointestinal symptoms that mimic cholera: vomiting and severe diarrhea (which may be rice-watery in character, often bloody). The acutely intoxicated patient will be in acute distress, often dehydrated and in hypovolemic shock.
Chronic toxicity is more insidious and may present as a classical dermatitis: hyperkeratosis with a classical dew drops on a dusty road appearance or peripheral neuropathy: classically a painful paresthesia which is symmetrical and stocking-glove in distribution. Also, whitish lines (Mees lines) which look very much like traumatic injuries are found on the fingernails.
The use of chelation therapy is imperative in all symptomatic arsenic poisoning. The key to the treatment of arsenic toxicity is chelation therapy with DMSA capsule. DMSA capsule binds arsenic and hastens its excretion. DMSA capsule can be used as an arsenic chelator and can be efficacious in treating arsenic intoxications. DMSA capsule is used to supply sulphydryl groups to which arsenic can attach and may subsequently be eliminated from the body.
FORMULATION FOR DMSA CAPSULE AS PHARMACEUTICAL FORM
LEAFLET FOR PATIENT
Description: DMSA is an orally active arsenic chelating agent by forming water-soluble chelates and increasing the urinary excretion of arsenic.
Directions: Take as directed by a physician. Maintain adequate fluid intake. Take one capsule on an empty stomach every six hours interval for three weeks. Children can be administered (twice daily) dosage by separating capsules and sprinkling on soft food and following with some drinks. All patients are advised to drink more water for better excretion.
Side Effects: Nausea, vomiting, diarrhea, loose stools, metallic taste in mouth, hemorrhoids, rash, stomach and abdomen cramps, flu like symptoms, headache. Consult a physician if bothersome effects.
LEAFLET FOR PHYSICIANS
Physicians are requested first to observe the following symptoms then advise the patients to take the DMSA capsules for arsenic toxicity for the treatment according to the direction on the leaflet for patient for three weeks.
|Signs||:||Mees' Lines in fingernails.|
|Cardiovascular||:||Vasodilation, increased capillary permeability.|
|Blackfoot Disease||:||Gangrene of extremities.|
|Diarrhea||:||Rice-water stools,abdominal distress.|
|Dermatitis||:||Hyperkeratosis of palms and soles, boils, hyper-pigmentation with long-term exposure.|
|Cancer||:||Squamous cell carcinoma, Basal-cell carcinoma, Lung cancer.|