103577-45-3 Usage
Description
Lansoprazole, a proton pump inhibitor (PPI) similar to omeprazole, is a white to brownish white, odorless crystalline powder that is practically insoluble in water. It is a weak base (pyridine N, pKa 3.83) and a weak acid (benzimidazole N-H, pK 0.62). Lansoprazole is essentially a prodrug that, in the acidic biophase of the parietal cell, forms an active metabolite that irreversibly interacts with the target ATPase of the pump. It is used to inhibit gastric acid secretion, increasing intragastric pH, and is widely used in the therapy of gastroesophageal reflux and peptic ulcer disease. Lansoprazole is a racemic mixture of (R)and (S)-isomers, and its plasma elimination half-life is not proportional to the duration of the drug's effects.
Uses
1. Used as a gastric proton pump inhibitor and an antiulcerative.
2. Used in the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastrointestinal bleeds with NSAID use.
3. Used in the treatment of gastroesophageal reflux disease (GERD), erosive esophagitis, duodenal ulcers, Helicobacter pylori (H. pylori) infections, stomach ulcers, and prevention of stomach ulcers in those people taking non-steroidal anti-inflammatory drugs (NSAIDs).
4. Used as an H+,K+-ATPase inhibitor that displays antisecretory activity.
Application Industries:
1. Pharmaceutical Industry: Lansoprazole is used for the treatment of various gastrointestinal disorders, such as GERD, erosive esophagitis, stomach ulcers, duodenal ulcers, H. pylori infections, and Zollinger-Ellison syndrome.
2. Medical Industry: Lansoprazole is used to prevent gastrointestinal bleeds in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and to treat acid-reflux disorders.
Brief Introduction
Lansoprazole is in a class of drugs called proton pump inhibitors (PPI) which prevent the stomach from producing gastric acid.The other drugs in PPI family include:
rabeprazole (Aciphex),
omeprazole (Prilosec),
pantoprazole (Protonix),
esomeprazole (Nexium).
Proton pump inhibitors are used for the treatment of conditions such as ulcers, gastroesophageal reflux disease (GERD) and Zollinger-Ellison syndrome that are caused by stomach acid. Lansoprazole, like other proton-pump inhibitors, blocks the enzyme in the
wall of the stomach that produces acid. By blocking the enzyme, the production of acid is decreased, and this allows the stomach and esophagus to heal.
Gastric acid secretion inhibitor
R-(+)-Lansoprazole is the dextroisomer of lansoprazole and a kind of anti-ulcer drug. It is the substitution product of benzimidazole derivative byimporting the fluorine element in the molecular structure and the is the second proton pump inhibitor after omeprazole.? R-(+)-Lansoprazole has a better inhibitory effect for gastric acid secretion than that of other drugs (omeprazole, pantoprazole, rabeprazole) and it can significantly inhibit ulcer. It has a better Curative effect for ethanol-induced gastric mucosa lesion and acid hypersecretion induced duodenal ulcer than that of famotidine and omeprazole. In addition, This product also has an anti-Helicobacter pylori effect similar to that of Bismuth preparations and can be used to treat reflux esophagitis and Zollinger-Ellison syndrome.
pharmacodynamics???
R-(+)-Lansoprazole can transform into active sulfonamide derivatives. In the tubule acidic environment of parietal cells, which are connected to the sulfydryl of H+-K+-(ATP)adenosine triphosphatase(the last step of the enzyme catalyzed gastric acid secretion process),passivat H+-K+-ATP enzyme and Inhibit the gastric acid secretion regulated by central and peripheral nervous systems. The inhibition effect of gastric acid secretion of this product is at least as strong as omeprazole. In vivo studies of animal model have demonstrated that the inhibition effect for gastric acid secretion of R-(+)-Lansoprazole is inferior to H2 receptor antagonist ranitidine and famotidine, but just as effective as omeprazole. Unlike the H2 receptor antagonist, whether taken in the morning or evening, this product can inhibit gastric acid secretion during the day and night. It can also reduce the gastric acid secretion, inhibit the secretion of pepsin and its activity and clear pyloric campylobacter on gastric mucosa (A bacterium of causing recurrence. of peptic ulcer).
It can also be used to treat Helicobacter pylori infection, alongside antibiotics as adjunctive treatment, to kill H. pylori causing ulcers or other problems involves using two other drugs known as "triple therapy", and involves taking twice daily for 10 or 14 days lansoprazole, amoxicillin, and clarithromycin.
Pharmacokinetics
When this product transform into active AG-1812 and AG-2000, R-(+)-Lansoprazole in serum is metabolized quickly and completely into two main faeces: Lansoprazole sulfone and hydroxy orchid sola. About 14%~23% of doses are excreted in the urine as conjugated and non-conjugated hydroxylation metabolites and no prototype of this product is found. The half-life of this product is 1.3~1.7 h, about 2 h for elderly people and as long as 7 h for patients with severe liver failure. The Peak blood concentration can reach 1038μg/L within 2 h after taking 30 mg enteric capsules of this product.
Marketing internationally
The lansoprazole molecule is off-patent and so generic drugs are available under many brand names in many countries;there are patents covering some formulations in effect as of 2015.
Since 2009, lansoprazole has been sold over the counter (OTC) in the U.S. in a marketed by Novartis as Prevacid 24HR. In Australia, it is being marketed by Pfizer as Zoton.
Clinical application
Applied to reflux esophagitis, gastric ulcer, duodenal ulcer. Patients with duodenal ulcer take this product 30 mg a day for a period of 2~4 weeks. An cure efficiency rate of 75%~100% can be achieved.It cures faster than famotidine and omeprazole and reduces ulcers-induced pain faster thanranitidine. Taking this product 30 mg a day can effectively treat reflux esophagitis and the cure rates after 4 weeks and 8 weeks can reach? 63%~84% and 85%~92% respectively. The cure effect for reflux esophagitis of this product is better than ranitidine and comparative to omeprazole. After 4 weeks treatment, the alleviation effect for heartburn symptoms of this product is much better than that of ranitidine and omeprazole. R-(+)-Lansoprazole can effectively treat patients with Peptic ulcer and reflux esophagitis whom cannot be cured by H2 receptor antagonist. A cure rate of 69%~100% can be achieved by taking this product 30 mg a day for a period of 8 weeks. A higher cure rate can be achieved if the dosage is increased to 30mg a day.
Drug interactions
1. Take R-(+)-Lansoprazole in conjunction with acetaminophen can increase the Peak blood concentration and shorten the time to peak.
2. Take R-(+)-Lansoprazole in conjunction with Roxithromycin can increase the local concentration of the latter and has a synergistic effect when treating Hp infection.
3. Take R-(+)-Lansoprazole in conjunction with antacids can reduce the bioavailability of this product. If necessary, this product should be taken after 1 hour use of antacids.
4. Take R-(+)-Lansoprazole in conjunction with theophylline can slightly reduce the? blood concentrations of theophylline.
5. R-(+)-Lansoprazole can inhibit gastric acid secretion significantly and persistently, thereby reduce the absorption of itraconazole and ketoconazole. So they should not be used at the same time.
6. Sucralfate may interfere the absorption of this product and reduce its bioavailability. So this product should be taken at least 30 minutes before taking sucralfate.
7. Take R-(+)-Lansoprazole in conjunction with clarithromycin may cause? Glossitis, stomatitis and black tongue. Patients should pay attention to the change of oral mucosa , stop using clarithromycin and reduce the dose of this product if necessary.
Adverse reactions
This product can cause constipation, diarrhea, dry mouth, abdominal distention, anemia, increased white blood cells and eosinophils, thrombocytopenia, elevated liver enzymes, headache, drowsiness, insomnia, skin rashes, itching, etc., and occasionally cause fever, increased total cholesterol and uric acid value, etc.
Cautions
1.This drug is forbidden for those who are allergic to this product, pregnant and lactant women. Patients with a history of drug allergy
and hepatic insufficiency should use this product with caution.
2.Elderly patients with medication must be closely observed
3.This product may mask the stomach cancer symptoms. Therefore, this product should be taken before excluding stomach cancer.
Originator
Takeda (Japan)
Manufacturing Process
Preparation of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-1Hbenzimidazole:A mixture of 6.63 g of 2-hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)
pyridine (30 mmol), 4.5 g of 2-mercaptobenzimidazol (30 mmol) and 8.67 g
of triphenylphosphine (33 mmol) was dissolved in 100 ml of tetrahydrofuran,
5.75 g of diethyl azodicarboxylate (33 mmol) dissolved in 30 ml of
tetrahydrofuran was added dropwise thereto at room temperature, and stirred
for 1 hour. The reaction mixture was concentrated under a reduced pressure,
the resulting residue was combined with 100 ml of ethylacetate, and extracted
twice with 50 ml portions of 1 N HCl. The aqueous layer was then washed
with 50 ml of diethylether; neutralized with 1 N NaOH to adjust the pH to 7.
The resulting precipitates were filtrated, washed with water, and dried, to
obtain 10.06 g of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-
1H-benzimidazole as a white solid (yield: 95%), m.p.142-144°C.4.46 g of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-1Hbenzimidazole (12 mmol) and 18.74 mg of tetramethyl-1-piperidinyloxy free
radical (1 mol %, used as a catalyst) were dissolved in 40 ml of
tetrahydrofuran, and combined with 166.76 mg of tetrabutylammonium
chloride (5 mol %) dissolved in 20 ml of distilled water. The resulting mixture
was cooled to 0°C and 13.6 ml of NaOCl (12%, 2.2 equivalent) dissolved in 20
ml of distilled water was added thereto over 2 hours at 0°C, stirred for 10
min, and then for additional 10 min at 20°C. Then, the reaction mixture was
extracted with 40 ml of ethylacetate and the organic layer was washed with
sat. NaHCO3 (30 ml) and then with sat. brine (30 ml), dried over anhydrous
MgSO4, and the solvent was removed therefrom. The resulting crude product
as recrystallized from acetone/hexane, to obtain 3.99 g of 2-[3-methyl-4-
(2,2,2-trifluoroethoxy)-2-pyridyl]methylsulphinyl-1H-benzimidazol
(lansoprazole) as a white-light brown solid (yield: 90%), melting point 164-
165°C (decomposition).
Therapeutic Function
Antiulcer
Biological Activity
H + ,K + -ATPase inhibitor (IC 50 = 6.3 μ M) that displays antisecretory and antiulcer activity. Inhibits gastric acid secretion (IC 50 = 0.09 μ M for histamine-induced acid formation) and reduces gastric lesion formation induced by a variety of ulcerative stimuli. Antibacterial against Helicobacter pylori in vitro . Also blocks swelling-dependent chloride channel (ICIswell) in NIH3T3 fibroblasts. More potent than omeprazole (5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole ).
Biochem/physiol Actions
Gastric proton pump inhibitor.
Check Digit Verification of cas no
The CAS Registry Mumber 103577-45-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,3,5,7 and 7 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 103577-45:
(8*1)+(7*0)+(6*3)+(5*5)+(4*7)+(3*7)+(2*4)+(1*5)=113
113 % 10 = 3
So 103577-45-3 is a valid CAS Registry Number.
InChI:InChI=1/C17H14F3N3O2/c1-10-13(21-7-6-15(10)25-9-17(18,19)20)8-14(24)16-22-11-4-2-3-5-12(11)23-16/h2-7H,8-9H2,1H3,(H,22,23)
103577-45-3Relevant articles and documents
Synthesis method of lansoprazole
-
Paragraph 0047-0075, (2021/04/28)
The invention discloses a synthesis method of lansoprazole, which comprises the following steps: condensing 2-mercaptobenzimidazole and 2-chloromethyl-3-methyl-4-(2, 2, 2-trifluoroethoxy) pyridine hydrochloride under alkaline conditions, oxidizing by a one-pot method to obtain a lansoprazole crude product, and finally refining to obtain the lansoprazole refined product. The method solves the problems that many three wastes are generated in lansoprazole production, a plurality of refining is needed, and drying deterioration is easily caused; the method is mild in reaction conditions, the total molar yield is 92% or above, the HPLC is 99.9% or above, and the method is suitable for industrial large-scale production.
Stable high-purity (R)-Lansoprazole, and preparation method thereof
-
Paragraph 0056-0058, (2019/09/14)
The invention provides (R)-Lansoprazole with a purity of 99.5% or higher. The preparation method comprises following steps: a (R)-Lansoprazole crude product is dissolved in a refined solvent system, dissolving and condensation are carried out, and then crystallization, filtering, and impurity removing are carried out to obtain refined (R)-Lansoprazole, wherein in the dissolving preparation process, an alkaline stabilizing agent 1 is added, and in the condensation process, an alkaline stabilizing agent 2 is added, so that the impurity I content of the obtained (R)-Lansoprazole refined product is lower than 0.1%, degradation impurity introduction is controlled preferably, in long term storage process, the obtained product is capable of satisfying medicine purity requirements, the controllability is high, and a quality control problem of (R)-Lansoprazole in industrialized production is solved.
Preparation method of dexlansoprazole
-
Paragraph 0054; 0055; 0056, (2018/08/04)
The invention relates to a preparation method of dexlansoprazole. The method includes: preparation of the formula (I) compound into dexlansoprazole by substitution in the presence of a trifluoroethanol metal salt. The method has a simple process, and can acquire high yield and high purity dexlansoprazole without column chromatography, and is very suitable for industrial mass production.