Benfotiamine

Chemical properties

crystals

Originator

Biotamin,Sankyo

The Uses of Benfotiamine

Vitamin B1 analog. Synthetic S-acyl derivative of Thiamine (T344185).

The Uses of Benfotiamine

S-Benzoylthiamine O-monophosphate has been used to determine its effect on ischemia and reperfusion in skeletal muscles of rat.

Background

Benfotiamine has been investigated for the treatment and prevention of Diabetic Nephropathy and Diabetes Mellitus, Type 2.

What are the applications of Application

Benfotiamine is a lipid-soluble thiamine derivative

Definition

ChEBI: A thioester that is a synthetic analogue of thiamine obtained by acylative cleavage of the thiazole ring and O-phospohorylation.

Manufacturing Process

28.6 g 84% phosphoric acid was heated to temperature about 270°C. After cooling to 100°C 4 g thiamine hydrochloride (vitamin B1 hydrochloride) was added and left at temperature 100°C before an isolation of HCl was ended. After adding of an ice water and acetone, phosphate ester of vitamin B1 was fallen. The precipitate was dissolved in 17 ml 1 N HCl and stood at ambient temperature 7 days for a hydrolysis. Then a solution was with acetone diluted and the mixture was cooled, whereupon vitamin B1 monophosphate hydrochloride was isolated.
The solution of 4.3 parts vitamin B1 monophosphate hydrochloride in 16 parts of water was diluted with 11 parts 15% NaOH, 2.1 parts benzoyl chloride was dropwise added with stirring and cooling. The obtained mixture was neutralized, evaporated in vacuum, acidified with concentrated HCl to pH 3.5- 4, whereupon a crude S-derivative of vitamin B1 monophosphate ester was precipitated. The product was suspended in water, was bringing with NaOH to pH 7 and was acidified to pH 4. 3.4 g refined S-benzoylthiamine Omonophosphate was prepared; MP: 165°C (with decomposition).

Therapeutic Function

Analgesic

General Description

S-Benzoylthiamine O-monophosphate (Benfotiamine) is an amphiphilic S-acyl thiamine derivative. It is a lipid-soluble vitamin. Benfotiamine?contains a thiazole ring. Benfotiamine has a greater bioavailability than thiamine.

Biochem/physiol Actions

S-Benzoylthiamine O-monophosphate (Benfotiamine) is a therapeutic agent. It helps in the prevention of diabetic complications such as, retinopathy, neuropathy and nephropathy. Benfotiamine inhibits the synthesis of glycation end products (AGEs) in diabetes. Benfotiamine is considered as a nutraceutical product for the prevention of diabetic neuropathy.

Mechanism of action

Benfotiamine acts by modulating the advanced glycation end products (AGEs). It can also act through non-AGE-dependent pathways. Advanced glycation end products are modified proteins or lipids that become non-enzymatically glycated on exposure to sugars such as aldose. AGEs may generate reactive oxygen species, attach to specific receptors, and form cross-linking structures. AGEs are present in the diabetic vasculature and are involved in the progression of atherosclerosis. Benfotiamine inhibits the synthesis of AGEs and thus decreases metabolic stress. Benfotiamine thus helps in vascular complications associated with diabetes. Benfotiamine can also regulate non-AGE dependent pathways such as nuclear transcription Factor κB, vascular endothelial growth factor receptor 2, and glycogen synthase kinase-3β (GSK-3β). It can also modulate mechanisms related to cell survival, repair, and apoptosis.

Metabolism

When administered orally, benfotiamine is dephosphorylated by alkaline phosphatases in the intestine to S-benzoylthiamine, which is lipophilic and can cross cell membranes. S-Benzoylthiamine diffuses through the intestinal epithelium into the bloodstream, which is converted to free thiamine by erythrocytes. Because thiamine absorption is limited by thiamine transporters, oral administration of benfotiamine results in higher plasma concentrations of thiamine than oral administration of equal concentrations of thiamine itself; for this reason, benfotiamine is frequently used in conditions characterized by thiamine deficiency (TD).

Side Effects

Side effects noted with Benfotiamine are skin irritation, allergic reactions, shortness of breath, difficulty in swallowing, feeling of discomfort, rash, itching, cough, decreased blood pressure, facial swelling, increased sweating, restlessness, weakness, and wheezing.