Ambroxol

Kirchner, F.K. U.S. Patent 3JD96.373 July 2,1963 assigned to Sterling Drug Inc. 

Chemical Name 4-[[(2-Amino-3,5-dlbromophenyl)methyl]amino] yclohexanol Common Name — 

5 g of N-(trans-p-hydroxy yclohexyl)-(2-aminobenzyl)-amine were dissolved in a mixture of 80 cc of glacial acetic acid and 20 cc of water, and then 9.6 g of bromine were added drop-wise at room temperature while stirring the solution. After all of the bromine had been added, the reaction mixture was stirred for two hours more and was then concentrated in a water aspirator vacuum. The residue was taken up in 2 N ammonia, the solution was extracted several times with chloroform, and the organic extract solutions were combined and evaporated. The residue, raw N-(trans-p-hydroxy yclohexyl)-(2-amino-3,5-dibromobenzyl)-amine, was purified with chloroform and ethyl acetate over silica gel in a chromatographic column, the purified product was dissolved in a mixture of ethanol and ether, and the solution was 

N-(tran -p-hydroxy-cyclohexyl)-(2-aminobenzyl)-amine Bromine 

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Ambroxol [18683-91 -5] (24), a metabolite of bromhexiae, has also shown potent clinical activity (28). Various esters of ambroxol have been shown to be 1.1 to 1.6 times more active as expectorants than ambroxol (29). The esters also show better gastric tolerabiUty and more rapid absorbtion than ambroxol. 

Developed standai d validation procedure is demonstrated for validation of a spectrophotometric assay of ambroxol hydrochloride tablets. Without any considerable revisions, this approach may be applied to chromatographic methods. Recommendations for validation criteria were included in the State Phai macopoeia of Ukraine. 

Mucolytic and anti-oxidant drugs include ambroxol, N-acetylcysteine, carbocysteine and iodinated glycerol. These drugs have no proven effect on lung function. At... 

Compounds also found active include (among many others) tannins,145 the pharmaceutical products pyrimethamine (51, Scheme 15),146 ambroxol (52),147 the secre-tolytic ingredient in mucosolvan, or fluphenazine (53),147 an antipsychotic substance, as well as—and closer to real sugars—ascorbic acid derivatives (54).148... 

Bromhexine 8 mg TDS (used with ambroxol and cetirizine also)... 

Ranunculaceae) Adhatoda Vasica (Acanthaceae) India Leaf Bromhexine Ambroxol (semisynthetic derivatives of alkaloid vasicine)... 

Fig. 2.19. Illustration of selectivity gain in CEC compared with micro HPLC (taken from Ref. [56] with permission of the publisher). Column Waters Spherisorb ODS I, 3 pm, 250 (335) x 0.1 mm. Mobile phase, 80% acetonitrile-20% 25 mM phosphate, 0.2% hexylamine, pH 3.8. Voltage 25 kV, temperature 20°C. Sample 1, procaine 2, timolol 3, ambroxol 4, metoclopramide 5, thiourea 6, naproxene 7, antipyrine.

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