CN103044333A - Preparation method of high-purity sodium ozagrel - Google Patents
Preparation method of high-purity sodium ozagrel Download PDFInfo
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- CN103044333A CN103044333A CN2013100102617A CN201310010261A CN103044333A CN 103044333 A CN103044333 A CN 103044333A CN 2013100102617 A CN2013100102617 A CN 2013100102617A CN 201310010261 A CN201310010261 A CN 201310010261A CN 103044333 A CN103044333 A CN 103044333A
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Abstract
The invention relates to a preparation method of high-purity sodium ozagrel, which comprises the following steps: dissolving ozagrel in a sodium hydroxide solution, filtering, concentrating, and carrying out vacuum filtration to obtain the high-purity sodium ozagrel. The method is simple to operate, and has the advantages of low cost and simple equipment requirements; and the produced sodium ozagrel has the advantages of high concentration and favorable clarity.
Description
Technical field
The present invention relates to medical technical field, particularly relate to a kind of preparation method of high purity Sodium Ozagrel.
Background technology
Sodium Ozagrel is a kind of dyskinesia that acute thrombotic cerebral infarction and cerebral infarction are followed for the treatment of, and is a kind of injectable drug, so require higher to its clarity.
Prepare in the world at present high purity Sodium Ozagrel method shortcoming is all arranged, be to mention in the patent of 200810132212.X the Sodium Ozagrel crude product is dissolved in 70～99.9% ethanol 75-85 degree centigrade the time such as the patent No., the applicant finds that in practice this method is unfeasible, because Sodium Ozagrel is almost insoluble in ethanol.The patent No. is to mention in 200910229627.3 the patent in the water dispersion of Sodium Ozagrel dripping NaOH solution, but still can not solve the clarity problem through repeatedly putting into practice, because the PH of Sodium Ozagrel is in acceptability limit, there is the part ozagrel not generate Sodium Ozagrel, so clarity does not reach requirement.How to prepare clarity preferably the high density Sodium Ozagrel be the problem of now needs solution.
Summary of the invention
Purpose of the present invention is exactly the preparation method that a kind of high purity Sodium Ozagrel is provided for the defective of above-mentioned existence.Use sodium hydroxide solution dissolving ozagrel, again through filtration, concentrated, suction filtration obtains the high purity Sodium Ozagrel.Simple to operate, with low cost, device requirement is simple, and the ozagrel na concn of production is high, and clarity is good.
Preparation method's technical scheme of a kind of high purity Sodium Ozagrel of the present invention is, uses sodium hydroxide solution dissolving ozagrel, again through filtration, concentrated, suction filtration obtains the high purity Sodium Ozagrel.
Method of the present invention may further comprise the steps:
(1) ozagrel is added in the sodium hydroxide solution stirring and dissolving clarification.
(2) the lysate thick activated carbon carbon-coating filtration treatment of 20mm～30mm;
(3) filtrate is in 60 ℃～80 ℃ concentrating under reduced pressure, when having a large amount of crystal to occur, stops to concentrate;
(4) enriched material suction filtration, the solid that obtains use the alcohol bubble to wash twice, and suction filtration goes out solid again.
(5) solid that obtains can obtain the high density Sodium Ozagrel in 50 ℃～60 ℃ decompression dryings 6～8 hours.
Sodium hydroxide solution is 10%～20% sodium hydroxide solution in the step (1).
The mass ratio of ozagrel and sodium hydroxide solution is 1:4～1:6 in the step (1).
Alcohol in the step (4) is methyl alcohol or ethanol.
Beneficial effect of the present invention is: a kind of high purity Sodium Ozagrel of the present invention, use sodium hydroxide solution dissolving ozagrel, again through filtration, concentrated, suction filtration obtains the high purity Sodium Ozagrel.The advantages such as the inventive method has simple to operate, and is with low cost, and device requirement is simple.The ozagrel na concn of producing is high, and clarity is good, and Sodium Ozagrel purity reaches more than 99.9%, and clarity is far smaller than 0.5.Sodium Ozagrel of the present invention, chemistry is by name; Trans-3-4-(1H-imidazolyl-1-methyl) cinnamylic acid sodium; Molecular formula is; C13H11N2O2Na; Chemical structure is:
Description of drawings
Figure 1 shows that the high performance liquid phase collection of illustrative plates of the product that the present invention obtains.
Embodiment:
In order to understand better the present invention, the below describes technical scheme of the present invention in detail with specific examples, but the present invention is not limited thereto.
The preparation method of a kind of high purity Sodium Ozagrel of the present invention is;
(1) 100 gram ozagrels is added in the sodium hydroxide solution of 500ml10% the stirring and dissolving clarification.
(2) the lysate thick egression A activated carbon carbon-coating filtration treatment of 20mm;
(3) filtrate is in 65 ℃ of concentrating under reduced pressure, when having a large amount of crystal to occur, stops to concentrate;
(4) enriched material suction filtration, the solid that obtains use the methyl alcohol bubble to wash twice, and suction filtration goes out solid again.
(5) solid that obtains obtains meeting Sodium Ozagrel 37 grams of JP16 standard in 50 ℃ of decompression dryings 6 hours.Sodium Ozagrel purity reaches more than 99.9%, and clarity is far smaller than 0.5.
Embodiment 2
The preparation method of a kind of high purity Sodium Ozagrel of the present invention is;
(1) 150 gram ozagrels is added in 15% the sodium hydroxide solution of 700ml the stirring and dissolving clarification.
(2) the lysate thick egression A activated carbon carbon-coating filtration treatment of 20mm;
(3) filtrate is in 70 ℃ of concentrating under reduced pressure, when having a large amount of crystal to occur, stops to concentrate;
(4) enriched material suction filtration, the solid that obtains use the ethanol bubble to wash twice, and suction filtration goes out solid again.
(5) solid that obtains obtains meeting Sodium Ozagrel 57 grams of JP16 standard in 60 ℃ of decompression dryings 8 hours.Sodium Ozagrel purity reaches more than 99.9%, and clarity is far smaller than 0.5.
Embodiment 3
The preparation method of a kind of high purity Sodium Ozagrel of the present invention is;
(1) 200 gram ozagrels is added in 20% the sodium hydroxide solution of 500ml the stirring and dissolving clarification.
(2) the lysate thick egression Z activated carbon carbon-coating filtration treatment of 20mm;
(3) filtrate is in 80 ℃ of concentrating under reduced pressure, when having a large amount of crystal to occur, stops to concentrate;
(4) enriched material suction filtration, the solid that obtains use the ethanol bubble to wash twice, and suction filtration goes out solid again.
(5) solid that obtains obtains meeting Sodium Ozagrel 78 grams of JP16 standard in 55 ℃ of decompression dryings 8 hours.Sodium Ozagrel purity reaches more than 99.9%, and clarity is far smaller than 0.5.
Claims (5)
1. the preparation method of a high purity Sodium Ozagrel is characterized in that, uses sodium hydroxide solution dissolving ozagrel, again through filtration, concentrated, suction filtration obtains the high purity Sodium Ozagrel.
2. the preparation method of a kind of high purity Sodium Ozagrel according to claim 1 is characterized in that, may further comprise the steps:
(1) ozagrel is added in the sodium hydroxide solution stirring and dissolving clarification;
(2) the lysate thick activated carbon carbon-coating filtration treatment of 20mm～30mm;
(3) filtrate is in 60 ℃～80 ℃ concentrating under reduced pressure, when having a large amount of crystal to occur, stops to concentrate;
(4) enriched material suction filtration, the solid that obtains use the alcohol bubble to wash twice, and suction filtration goes out solid again;
(5) solid that obtains can obtain the high density Sodium Ozagrel in 50 ℃～60 ℃ decompression dryings 6～8 hours.
3. the preparation method of a kind of high purity Sodium Ozagrel according to claim 2 is characterized in that, sodium hydroxide solution is 10%～20% sodium hydroxide solution in the step (1).
4. the preparation method of a kind of high purity Sodium Ozagrel according to claim 2 is characterized in that, the mass ratio of ozagrel and sodium hydroxide solution is 1:4～1:6 in the step (1).
5. the preparation method of a kind of high purity Sodium Ozagrel according to claim 2 is characterized in that, the alcohol in the step (4) is methyl alcohol or ethanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2013100102617A CN103044333A (en) | 2013-01-11 | 2013-01-11 | Preparation method of high-purity sodium ozagrel |
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| CN2013100102617A CN103044333A (en) | 2013-01-11 | 2013-01-11 | Preparation method of high-purity sodium ozagrel |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232395A (en) * | 2013-05-03 | 2013-08-07 | 四川省惠达药业有限公司 | Sodium ozagrel compound, preparation method and drug composition thereof |
| CN105481772A (en) * | 2016-02-03 | 2016-04-13 | 郭琨 | Ozagrel sodium crystal type compound |
| CN113956203A (en) * | 2021-11-25 | 2022-01-21 | 天津太平洋化学制药有限公司 | Novel crystal form compound of ozagrel sodium, preparation method and application thereof |
Citations (7)
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| US4469865A (en) * | 1981-09-28 | 1984-09-04 | Kissei Pharmaceutical Co., Ltd. | 1,3-Disubstituted imidazoles |
| JPH11269151A (en) * | 1998-02-16 | 1999-10-05 | Eerejieeru Spa | Preparation of 3-(4(1-h-imidazol-1-yl-methyl)phenyl)-2-propenoic acid and its salt |
| US20060122181A1 (en) * | 2003-04-09 | 2006-06-08 | Japan Tobacco Inc. | Heteroaromatic pentacyclic compound and medicinal use thereof |
| CN101659640A (en) * | 2009-02-24 | 2010-03-03 | 徐华 | Ozagrel tromethamine, compound, preparation method and application thereof |
| CN101704786A (en) * | 2009-10-28 | 2010-05-12 | 陶灵刚 | High-purity ozagrel compound |
| CN102276532A (en) * | 2011-08-26 | 2011-12-14 | 贺金凤 | Stable ozagrel sodium compound and medicinal composition thereof |
| CN102633723A (en) * | 2012-03-29 | 2012-08-15 | 西藏易明西雅生物医药科技有限公司 | Preparation method of ozagrel |
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2013
- 2013-01-11 CN CN2013100102617A patent/CN103044333A/en active Pending
Patent Citations (7)
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| US4469865A (en) * | 1981-09-28 | 1984-09-04 | Kissei Pharmaceutical Co., Ltd. | 1,3-Disubstituted imidazoles |
| JPH11269151A (en) * | 1998-02-16 | 1999-10-05 | Eerejieeru Spa | Preparation of 3-(4(1-h-imidazol-1-yl-methyl)phenyl)-2-propenoic acid and its salt |
| US20060122181A1 (en) * | 2003-04-09 | 2006-06-08 | Japan Tobacco Inc. | Heteroaromatic pentacyclic compound and medicinal use thereof |
| CN101659640A (en) * | 2009-02-24 | 2010-03-03 | 徐华 | Ozagrel tromethamine, compound, preparation method and application thereof |
| CN101704786A (en) * | 2009-10-28 | 2010-05-12 | 陶灵刚 | High-purity ozagrel compound |
| CN102276532A (en) * | 2011-08-26 | 2011-12-14 | 贺金凤 | Stable ozagrel sodium compound and medicinal composition thereof |
| CN102633723A (en) * | 2012-03-29 | 2012-08-15 | 西藏易明西雅生物医药科技有限公司 | Preparation method of ozagrel |
Non-Patent Citations (7)
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| CHUN GUO, 等: "An Improved and Convenient Procedure for the Synthesis of Ozagrel", 《CHINESE CHEMICAL LETTERS》 * |
| KINJI IIZUKA,等: "Highly Selective Inhibitors of Thromboxane Synthetase. 1. Imidazole Derivatives", 《J. MED. CHEM.》 * |
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| 王道林，等: "奥扎格雷钠的合成", 《中国医药工业杂志》 * |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232395A (en) * | 2013-05-03 | 2013-08-07 | 四川省惠达药业有限公司 | Sodium ozagrel compound, preparation method and drug composition thereof |
| CN105481772A (en) * | 2016-02-03 | 2016-04-13 | 郭琨 | Ozagrel sodium crystal type compound |
| CN105481772B (en) * | 2016-02-03 | 2016-08-31 | 郭琨 | A kind of sodium ozagrel crystal-form compound |
| CN113956203A (en) * | 2021-11-25 | 2022-01-21 | 天津太平洋化学制药有限公司 | Novel crystal form compound of ozagrel sodium, preparation method and application thereof |
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Application publication date: 20130417 |