| Title of Process/ Know-how/ Product/Design/Equipment

Cost-efficient non-infringing process for camostat mesylate

IPR Status & Details:

IN 202011047949

Application/Uses/Problem being addressed

Camostat mesylate acts as a serine protease inhibitor, which is active against the enzyme transmembrane protease serine 2 (TMPRSS2) partially blocked SARS-CoV-2 S-driven entry into lungs cells and full inhibition was attained when camostat mesylate is used in combination with other drugs. Thus, this compound has an envisaged use as a repurposed drug for the treatment of COVID-19. Currently the drug is under Phase-II clinical trial for the treatment of COVID-19 patients

Salient Technical Features including Competing Features/ Impact

Synthesis of camostat mesylate through the synthesis of its key intermediates, namely 2-(Dimethylamino)-2-oxoethyl 2-(4-hydroxyphenyl) acetate (Int-I) and 4-Guanidinobenzoic acid hydrochloride (Int-II), starting from inexpensive and indigenously available raw materials. The process is clean giving excellent yield and purity of both the compounds, Int-I and Int–II. The synthesis of both Int-I and Int-II have been performed at 50 g batch and are ready at 100 g level with purity >99% each.

The coupling between Int-I and Int-II gives the tosylate salt of camostat which is subsequently converted into camostat mesylate. The synthesis of camostat mesylate in solid form with 96% purity (hplc) has been achieved and reproduced in several 1 g batches. Currently efforts are ongoing to scale up the synthesis in up to 25 g batches

TRL Level & Scale of Development:- TRL 3 TRL Reference

Business scope & opportunity (in terms of scale, cost, market etc.)

Upon realization of 25 g batches with pharmaceutically relevant purity, identification of industry partner shall be explored.

Environmental Considerations

Not done yet

Status of Licensing:

Not yet licensed

Status of Commercialization:

Not yet licensed

Major Raw Materials Needed

Chloroacetyl chloride, N,N-dimethyl amine hydrochloride, 4-hydroxyphenylacetic acid, sodium hydroxide, potassium hydroxide, 4-aminobenzoic acid, cyanamide, Dicyclohexylcarbodiimide, p-toluenesulfonic acid, sodium bicarbonate, methanesulfonic acid

Major Plant Equipment and Machinery Required

Not yet figured out; process steps uses conventional reaction chemistry set up

Techno-Economics

  • A non-infringing process for camostat mesylate by utilising indigenously available raw materials.
  • Cost of the API production is proposed to be reduced by 20-30% of the existing process.
  • In Japan, the generic drug camostat mesylate costs 86,000 JPY/Kg = ~ ₹60,000/- per Kg.
  • Our proposed cost for camostat mesylate is ₹18,000 - 20,000/- per Kg (~96% pure) [based on 1 Kg production without considering any solvent/SM recovery. The cost will be further lowered when produced in a larger/industrial scale].
  • In India, both Int-I and Int-II are available at a price of ~₹26000/- and ₹21,000/- respectively per 500 g package. Gratifyingly, our proposed cost for Int-I is ₹7500/- per Kg and that for Int-II is ~₹3,000/- per Kg.
  • Technology Package

    Process for 2-(Dimethylamino)-2-oxoethyl 2-(4-hydroxyphenyl) acetate (KSM for camostat mesylate)

    Process for 4-Guanidinobenzoic acid hydrochloride

    Process for camostat mesylate (API)

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