Pharmaceutical Bulk Esomeprazole magnesium Powder

CAS:161973-10-0

MF: C34H36MgN6O6S2

MW:713.12 

EINECS:627-029-7

Specification: 99% min Esomeprazole magnesium Powder

Sample: Esomeprazole magnesium Powder

Packaging:1kg/bag, 25kg/drum

Brand: Henrikang

Appearance: White Powder

Storage: Cool Dry Place

Shelf Life: 2 Years

Test Method: HPLC

Esomeprazole magnesium  Powder Usage and Synthesis.

1. For gastroesophageal reflux disease (GERD). 2.

2. Treatment of erosive reflux oesophagitis.

3. Long-term maintenance therapy to prevent recurrence in patients with cured oesophagitis.

4. Symptom control of gastro-oesophageal reflux disease (GERD).

5. For the healing of peptic ulcers associated with eradication of Helicobacter pylori infection in combination with appropriate antimicrobial therapy and to prevent recurrence.

6. For reducing the risk of gastric ulcer development in patients on continuous NSAID therapy.

7. Used for the treatment of burning pain in the chest, stomach and epigastric region associated with liver-stomach disharmony.8. Used for the treatment of stomach pain and acid swallowing, choking and eructation.

Uses and functions of Esomeprazole magnesium.

Digestive disorders such as gastric ulcer, duodenal ulcer and reflux oesophagitis caused by excessive gastric acid secretion.

Pharmacological Effects of Esomeprazole magnesium.

1. Pharmacodynamic properties:

Esomeprazole is the S-isomer of omeprazole, which reduces gastric acid secretion through a specific targeted mechanism of action and is a specific inhibitor of the proton pump in mural cells. The R-isomer and S-isomer of omeprazole have similar pharmacodynamic properties.

2, Site and mechanism of action:

Esomeprazole is a weak base, which is concentrated and converted to the active form in the highly acidic environment of the acid-secreting microtubules of the mural cells, thus inhibiting the H+/K+-ATPase (proton pump) at this site, and inhibiting both basal gastric acid secretion and stimulated gastric acid secretion.

3, Effects on gastric acid secretion:

(1) Oral administration of esomeprazole 20 mg and 40 mg resulted in an onset of action within one hour. Repeated administration of 20 mg once daily for 5 consecutive days reduced the mean peak acid secretion induced by pentagastrin stimulation by 90% when measured 6-7 hours after the fifth day's dose.

(2) In symptomatic GERD patients, the mean 24-hour intragastric pH >4 after 5 days of oral esomeprazole 20 mg and 40 mg daily was 13 and 17 hours, respectively. The proportions of patients maintaining intragastric pH >4 for at least 8, 12, and 16 hours were 76%, 54%, and 24% at esomeprazole 20 mg; and 97%, 92%, and 56% at 40 mg, respectively.

(3) Using the AUC parameter instead of plasma drug concentration can show the quantitative relationship between gastric acid secretion inhibition and drug exposure.

4, Therapeutic effect of gastric acid inhibition:

(1) A clinical study has shown that the healing rate of patients with reflux oesophagitis taking esomeprazole 40 mg for 4 weeks was about 78% and 93% after 8 weeks.

(2) The eradication rate of H. pylori is approximately 90% after one week of treatment with esomeprazole 20 mg twice a day in combination with appropriate antimicrobials. After one week of eradication treatment, there is no need to follow up with acid suppressants alone for ulcer healing and symptom elimination in patients with uncomplicated duodenal ulcers.

5.Other effects associated with suppression of gastric acid:

(1) Decreased gastric acid secretion during treatment with antacid medications can lead to increased serum gastrin.

(2) In some patients on long-term treatment with esomeprazole, an increase in eosinophils (ECL cells) has been observed that may be associated with an increase in serum gastrin levels.

(3) Some increase in the incidence of gastric gland cysts has been reported during long-term treatment with antacids. These responses are physiological after significant inhibition of acid secretion, are benign in nature, and are considered reversible.

Production method of Bulk Esomeprazole magnesium Powder.

1, Esomeprazole magnesium synthetic route

Route 1 used asymmetric oxidation Esomeprazole, into potassium salt in methanol solution with magnesium sulfate reaction to prepare magnesium salt, but this method yield is low.

2, for the improved esomeprazole magnesium synthetic route operating steps are: (1) 5-methoxy-2-(4-methoxy-3,5-dimethyl-2-pyridinyl)methylthio-1H-benzimidazole (4) synthesis with electromagnetic stirring, thermometer, constant pressure dropping funnel and oil bath in a 500mL three-necked round-bottomed flask was added to the 2-mercapto-5-methoxy-1H-benzimidazole (3) ( 26.8 g, 0.15 mol), water 30 mL, sodium hydroxide (6.0 g, 0.15 mol) and methanol (200 mL), stirring to dissolve, then add 2-chloromethyl-3,5-dimethyl-4-methoxypyridine (2) (33.3 g, 0.15 mol), heating and stirring to reflux for 3 h. The reaction was completed, solvent was recovered under reduced pressure, acetone (25 mL) was added Stirring crystal precipitation, ice water bath stirring 1h, filtration, to get omepyrithione crude product (4).

The crude product was refluxed with ethyl acetate (200 mL) heating, filtered while hot, the filtrate was cooled down to precipitate crystals, filtered to obtain off-white solids; (2) the preparation of esomeprazole potassium salt (5) in 250mL four-necked vials add toluene (185mL), compound (4) (39.0g, 0.12mol), D-(-)-tartaric acid diethyl ester (4.3mL, 0.025 mol), and the mixture was heated to 50 ℃ with stirring. Heated to 50 °C with stirring, and reacted at this temperature for 20 mChemicalbookin; titanium isopropoxide (3.6 mL, 0.12 mol) was added, and the reaction was held for 45 min; the reaction solution was cooled to 30 °C, di-isopropylethylamine (3.1 mL, 0.018 mol) was added, and isopropylbenzene peroxide was added dropwise [20.0 g, 87% (GC method), and 0.12 mol], the titration rate was controlled to maintain the reaction temperature at 28~32°C; the reaction was continued for 2h after titration.

Add potassium methanol (12.3g, 0.18mol) solution (dissolved in 110mL methanol), stirring crystal precipitation; filtration, filter cake 35 ℃ vacuum drying, Esomeprazole potassium (5) (3) Esomeprazole magnesium crude (6) the preparation of Esomeprazole potassium salt crude 33g, dissolved in 60mL of water, slowly added 33mL (3.16mol / L) aqueous magnesium sulfate, drop after the reaction. After the drop, continue to stir the reaction for 1h, filtration, the filter cake was washed with 40mL of water, 40 ℃ vacuum drying esomeprazole magnesium crude (6) (4) Esomeprazole magnesium (1) refined Esomeprazole magnesium crude (6) (30g, 0.04mol) dissolved in methanol (90mL), stirring to dissolve, filtration, filtration, filtered out a few insoluble material, the filtrate plus ethyl acetate (300mL) stirring precipitation crystals. Filtration, the filter cake was washed with ethyl acetate (100mL), dried at 35 ℃, obtained esomeprazole magnesium 25.7g