CN114209697A - Proton pump inhibitor, preparation method and application - Google Patents
Proton pump inhibitor, preparation method and application Download PDFInfo
- Publication number
- CN114209697A CN114209697A CN202111524047.4A CN202111524047A CN114209697A CN 114209697 A CN114209697 A CN 114209697A CN 202111524047 A CN202111524047 A CN 202111524047A CN 114209697 A CN114209697 A CN 114209697A
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- Prior art keywords
- proton pump
- omeprazole
- pump inhibitor
- reaction solution
- solution
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention belongs to the technical field of oral care, and discloses a proton pump inhibitor, a preparation method and application thereof. The traditional Chinese medicine is novel in use, small in side effect, quick in effect taking and good in curative effect. The proton pump inhibitor and the omeprazole provided by the invention have high curative effect, are convenient to take, can effectively treat the dental ulcer, have great clinical significance and have prominent economic and social benefits. The proton pump inhibitor provided by the invention has the advantages of simple preparation process, low cost, mild reaction conditions, high synthesis efficiency, high yield, no need of biological enzyme, high safety, and effective improvement of the purity of the obtained proton pump inhibitor by purifying the omeprazole solution. The invention obviously increases the convenience of production operation, reduces operation steps, production energy consumption and time cost, reduces production cost, improves production efficiency and has high production economy.
Description
Technical Field
The invention belongs to the technical field of oral care, and particularly relates to a proton pump inhibitor, a preparation method and application thereof.
Background
At present, oral ulcer, commonly known as "aphtha", is a common ulcerative injury disease occurring in oral mucosa, which is mostly seen in the inner side of lip, tongue abdomen, buccal mucosa, vestibular sulcus, soft palate and other parts, and the mucosa of these parts lacks of cutinization layer or has poor keratosis. Tongue ulcer refers to oral ulcer occurring on tongue and tongue abdomen. The pain is severe when the oral ulcer is attacked, the local burning pain is obvious, and serious patients can influence diet and speaking, thereby causing great inconvenience to daily life; can be used for treating halitosis, chronic pharyngitis, constipation, headache, dizziness, nausea, asthenia, dysphoria, fever, and lymphadenectasis.
Canker sores develop as a result of a combination of factors including topical trauma, stress, food, medication, malnutrition, altered hormone levels, and vitamin or trace element deficiencies. Systemic diseases, heredity, immunity and microorganisms may play an important role in the development and development of oral ulcers. Western medicine treatment generally adopts oral administration of vitamins, 0.25% of aureomycin is absorbed in the mouth, corticosteroid hormone ointment or powder is coated, and patients with severe pain can absorb 1% of novocaine in the mouth or be attached to ulcer parts by various medicine films. The silver nitrate can corrode the local ulcer and relieve symptoms and promote healing. However, western medicine treatment has large irritation to oral mucosa and is easy to generate drug resistance after long-term use. Therefore, the development of a new oral care product with the function of resisting the oral ulcer is of great significance.
Through the above analysis, the problems and defects of the prior art are as follows: the currently used medicines have poor effects or large side effects; meanwhile, the existing preparation method of the proton pump inhibitor has the disadvantages of complicated process, high cost, low yield and low product purity.
The significance of solving the problems and the defects is as follows: the invention is used for new application of old medicine, and has the advantages of small side effect, quick effect and good curative effect.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a proton pump inhibitor, a preparation method and application thereof.
The invention is realized in that the proton pump inhibitor is omeprazole.
Another object of the present invention is to provide a method for preparing a proton pump inhibitor using the proton pump inhibitor, wherein the method for preparing the proton pump inhibitor comprises the following steps:
step one, reacting 2-sulfenyl-5-methoxybenzimidazole with 2-chloromethyl-3, 5-dimethyl-4-methoxypyridine hydrochloride in sodium hydroxide solution to generate an ormela thioether intermediate;
dissolving the intermediate of the omeprazole thioether by using ethanol, and reacting the intermediate with a catalyst and cumene hydroperoxide to obtain an omeprazole reaction solution;
purifying the obtained omeprazole reaction solution; adding sodium carbonate into the purified omeprazole reaction solution, uniformly mixing, and adjusting the pH value by using an acetic acid aqueous solution;
adding omeprazole seed crystals into the adjusted solution, stirring uniformly, continuously dropwise adding an acetic acid aqueous solution to adjust the pH value, and standing for aging for a period of time;
step five, filtering and separating the product, and washing the separated product by using a methanol water solution; and simultaneously, drying the washed product in vacuum to obtain the proton pump inhibitor.
Further, the catalyst is a catalyst containing ammonium molybdate.
Further, the purification of the obtained omeprazole reaction solution comprises:
recrystallizing the omeprazole reaction solution by using a mixed solution of sodium hydroxide and methanol; and filtering the obtained omeprazole reaction solution after recrystallization by using an ultrafiltration membrane to obtain the purified omeprazole reaction solution.
Further, the concentration of the aqueous acetic acid solution was 25%.
Further, in step four, the adjusting the pH comprises: the pH was adjusted to 8.5.
Further, in the fourth step, the aging time is 1 h.
Another object of the present invention is to provide a use of the proton pump inhibitor for the preparation of a medicament for the treatment of oral ulcers.
Further, the pharmaceutical dosage form for treating oral ulcer comprises tablets, capsules, granules, pills, syrups, oral solutions, oral suspensions or oral emulsions.
Another object of the present invention is to provide a use of the proton pump inhibitor in an oral care product.
By combining all the technical schemes, the invention has the advantages and positive effects that: the proton pump inhibitor and the omeprazole provided by the invention have high curative effect, are convenient to take, can effectively treat the dental ulcer, have great clinical significance and have prominent economic and social benefits. The proton pump inhibitor provided by the invention has the advantages of simple preparation process, low cost, mild reaction conditions, high synthesis efficiency, high yield, no need of biological enzyme, high safety, and effective improvement of the purity of the obtained proton pump inhibitor by purifying the omeprazole solution. The invention obviously increases the convenience of production operation, reduces operation steps, production energy consumption and time cost, reduces production cost, improves production efficiency and has high production economy.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments of the present invention will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
Fig. 1 is a flow chart of a method for preparing a proton pump inhibitor according to an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Aiming at the problems in the prior art, the invention provides a proton pump inhibitor, a preparation method and application thereof, and the invention is described in detail with reference to the accompanying drawings.
The proton pump inhibitor provided by the embodiment of the invention is omeprazole. The omeprazole powder is directly applied to the ulcer surface of a patient by external application.
As shown in fig. 1, the preparation method of the proton pump inhibitor provided by the embodiment of the present invention includes the following steps:
s101, 2-thioyl-5-methoxybenzimidazole reacts with 2-chloromethyl-3, 5-dimethyl-4-methoxypyridine hydrochloride in sodium hydroxide solution to generate an omeprazole thioether intermediate;
s102, dissolving the intermediate of the omeprazole thioether by using ethanol, and reacting the intermediate with a catalyst containing ammonium molybdate and cumene hydroperoxide to obtain an omeprazole reaction solution;
s103, purifying the obtained omeprazole reaction solution; adding sodium carbonate into the purified omeprazole reaction solution, uniformly mixing, and adjusting the pH value by using an acetic acid aqueous solution;
s104, adding omeprazole seed crystals into the adjusted solution, stirring uniformly, continuously dropwise adding an acetic acid water solution to adjust the pH value to 8.5, and standing for aging for 1 h;
s105, filtering and separating the product, and washing the separated product by using a methanol water solution; and simultaneously, drying the washed product in vacuum to obtain the proton pump inhibitor.
The purification of the obtained omeprazole reaction solution provided by the embodiment of the invention comprises the following steps:
recrystallizing the omeprazole reaction solution by using a mixed solution of sodium hydroxide and methanol; and filtering the obtained omeprazole reaction solution after recrystallization by using an ultrafiltration membrane to obtain the purified omeprazole reaction solution.
The concentration of the acetic acid aqueous solution provided by the embodiment of the invention is 25%.
The technical solution of the present invention is further described below with reference to specific examples.
Case 1:
name: shux sex: the date of the female visit: 2020.10.27
Diameter of 10mm 8.5mm
Pain before administration: half hour after 9 minutes of administration: 6 minutes
Case 2:
name: and what xx sex: the date of the male's visit: 2020.10.29
Diameter 10mm
Pain before administration: half hour after 7 minutes of administration: 5 points of
Case 3:
name: luxx sex: the date of the female visit: 2020.11.2
Diameter 5mm
Pain before administration: half hour after 6 minutes of administration: 4 is divided into
Case 4:
name: gender of Zhang xx: the date of the female visit: 2020.11.5
6mm diameter
Pain before administration: half hour after 5 minutes of administration: 1 minute (1)
Case 5:
name: forest x sex: the date of the male's visit: 2020.11.7
4mm 4m in diameter
Pain before administration: half hour after 5 minutes of administration: 4 is divided into
Case 6:
name: sex to xx: the date of the female visit: 11.7
Diameter 7mm 3m
Pain before administration: half hour after 5 minutes of administration: 4 is divided into
Case 7:
name: zhao xx gender: the date of the female visit: 2020.11.24
Diameter 11mm 5.5mm
Pain before administration: half hour after 6 minutes of administration: 0 point (min)
Case 8:
name: sex danxx: the date of the female visit: 2020.11.25
Diameter 5mm
Pain before administration: 8 minutes of administration is half an hour: 5 points of
The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A proton pump inhibitor, wherein said proton pump inhibitor is omeprazole.
2. A process for preparing the proton pump inhibiting agent of claim 1, wherein the process comprises the steps of:
step one, reacting 2-sulfenyl-5-methoxybenzimidazole with 2-chloromethyl-3, 5-dimethyl-4-methoxypyridine hydrochloride in sodium hydroxide solution to generate an ormela thioether intermediate;
dissolving the intermediate of the omeprazole thioether by using ethanol, and reacting the intermediate with a catalyst and cumene hydroperoxide to obtain an omeprazole reaction solution;
purifying the obtained omeprazole reaction solution; adding sodium carbonate into the purified omeprazole reaction solution, uniformly mixing, and adjusting the pH value by using an acetic acid aqueous solution;
adding omeprazole seed crystals into the adjusted solution, stirring uniformly, continuously dropwise adding an acetic acid aqueous solution to adjust the pH value, and standing for aging for a period of time;
step five, filtering and separating the product, and washing the separated product by using a methanol water solution; and simultaneously, drying the washed product in vacuum to obtain the proton pump inhibitor.
3. The method of preparing a proton pump inhibiting agent as recited in claim 2, wherein the catalyst is an ammonium molybdate-containing catalyst.
4. The process for preparing a proton pump inhibitor as claimed in claim 2, wherein the purifying the reaction solution of omeprazole obtained comprises:
recrystallizing the omeprazole reaction solution by using a mixed solution of sodium hydroxide and methanol; and filtering the obtained omeprazole reaction solution after recrystallization by using an ultrafiltration membrane to obtain the purified omeprazole reaction solution.
5. The method of preparing the proton pump inhibiting agent of claim 2, wherein the aqueous acetic acid is 25% concentrated.
6. The process for preparing a proton pump inhibiting agent as claimed in claim 2, wherein in step four, the adjusting the pH comprises: the pH was adjusted to 8.5.
7. The process for preparing a proton pump inhibitor as claimed in claim 2, wherein in step four, the aging time is 1 hour.
8. Use of a proton pump inhibitor as defined in claim 1 in the manufacture of a medicament for the treatment of oral ulcers.
9. The use of the proton pump inhibitor according to claim 8 for the preparation of a medicament for the treatment of oral ulcers, wherein the dosage form of the medicament for the treatment of oral ulcers comprises tablets, capsules, granules, pills, syrups, oral solutions, oral suspensions or oral emulsions.
10. Use of the proton pump inhibitor of claim 1 in an oral care product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111524047.4A CN114209697A (en) | 2021-12-14 | 2021-12-14 | Proton pump inhibitor, preparation method and application |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111524047.4A CN114209697A (en) | 2021-12-14 | 2021-12-14 | Proton pump inhibitor, preparation method and application |
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| CN114209697A true CN114209697A (en) | 2022-03-22 |
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| CN202111524047.4A Pending CN114209697A (en) | 2021-12-14 | 2021-12-14 | Proton pump inhibitor, preparation method and application |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1322201A (en) * | 1998-08-11 | 2001-11-14 | 麦克公司 | Improved omeprazole process and compositions thereof |
| US20100113526A1 (en) * | 2007-02-21 | 2010-05-06 | Cipla Limited | Process for the Preparation of Esomeprazole Magnesium Dihydrate |
| CN104370884A (en) * | 2014-10-29 | 2015-02-25 | 北京华睿鼎信科技有限公司 | Preparation method of esomeprazole magnesium dihydrate |
| CN106083819A (en) * | 2016-06-08 | 2016-11-09 | 扬子江药业集团有限公司 | A kind of preparation method of omeprazole |
| CN108440502A (en) * | 2018-05-04 | 2018-08-24 | 南京海润医药有限公司 | A method of preparing the related substance of Omeprazole Sodium |
| CN110372667A (en) * | 2019-08-26 | 2019-10-25 | 浙江金华康恩贝生物制药有限公司 | A kind of Omeprazole synthesis technology |
| CN111494232A (en) * | 2020-04-23 | 2020-08-07 | 苏州聚分享电子商贸有限公司 | Medicinal toothpaste for resisting helicobacter pylori |
| CN112679475A (en) * | 2021-01-14 | 2021-04-20 | 四川新迪医药化工有限公司 | Omeprazole preparation method and omeprazole |
-
2021
- 2021-12-14 CN CN202111524047.4A patent/CN114209697A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1322201A (en) * | 1998-08-11 | 2001-11-14 | 麦克公司 | Improved omeprazole process and compositions thereof |
| US20100113526A1 (en) * | 2007-02-21 | 2010-05-06 | Cipla Limited | Process for the Preparation of Esomeprazole Magnesium Dihydrate |
| CN104370884A (en) * | 2014-10-29 | 2015-02-25 | 北京华睿鼎信科技有限公司 | Preparation method of esomeprazole magnesium dihydrate |
| CN106083819A (en) * | 2016-06-08 | 2016-11-09 | 扬子江药业集团有限公司 | A kind of preparation method of omeprazole |
| CN108440502A (en) * | 2018-05-04 | 2018-08-24 | 南京海润医药有限公司 | A method of preparing the related substance of Omeprazole Sodium |
| CN110372667A (en) * | 2019-08-26 | 2019-10-25 | 浙江金华康恩贝生物制药有限公司 | A kind of Omeprazole synthesis technology |
| CN111494232A (en) * | 2020-04-23 | 2020-08-07 | 苏州聚分享电子商贸有限公司 | Medicinal toothpaste for resisting helicobacter pylori |
| CN112679475A (en) * | 2021-01-14 | 2021-04-20 | 四川新迪医药化工有限公司 | Omeprazole preparation method and omeprazole |
Non-Patent Citations (2)
| Title |
|---|
| 闫铁: "奥美拉唑肠溶胶囊可以治口腔溃疡吗？", pages 6 - 10, Retrieved from the Internet <URL:http://ask.39.net/question/44100232.html> * |
| 饶国武, 胡惟孝, 杨忠愚: "奥美拉唑的合成进展", 合成化学, no. 04, pages 297 - 301 * |
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