CN102503845A - Preparation method of DL-lysine aspirin salt and application thereof - Google Patents
Preparation method of DL-lysine aspirin salt and application thereof Download PDFInfo
- Publication number
- CN102503845A CN102503845A CN2011102964578A CN201110296457A CN102503845A CN 102503845 A CN102503845 A CN 102503845A CN 2011102964578 A CN2011102964578 A CN 2011102964578A CN 201110296457 A CN201110296457 A CN 201110296457A CN 102503845 A CN102503845 A CN 102503845A
- Authority
- CN
- China
- Prior art keywords
- preparation
- frosst
- aspisol
- salt
- methionin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Abstract
The invention discloses a preparation method of a DL-lysine aspirin salt and an application thereof. The preparation method comprises the following specific steps of: dissolving DL-lysine with water, keeping the final concentration of the DL-lysine at 30-35 percent by mass, and degerming to obtain a DL-lysine aqueous solution; dissolving aspirin with an organic solvent, keeping the final concentration of aspirin at 18-20 percent by mass, and degerming to obtain an aspirin organic solution; adding the DL-lysine aqueous solution into the aspirin organic solution, wherein the aspirin and the DL-lysine are mixed in the mass ratio of (1-1.2):1; fully reacting while stirring, and separating salts of DL-lysine and aspirin; and after separation is performed completely, separating to obtain salts of DL-lysine and aspirin, washing with an organic solvent, and drying to obtain the DL-lysine aspirin salt. The preparation method provided by the invention has low production cost and simple steps. A product obtained with the preparation method disclosed by the invention has the advantages of high yield, high quality, high stability and various indexes reaching the medicament standard of the Ministry of Health.
Description
Technical field
The present invention be more particularly directed to a kind of preparation method and application thereof of DL-Aspisol salt, belong to the field of chemical synthesis.
Background technology
DL-Aspisol salt is the ntipyretic analgesic medicine of domestic widespread use clinically at present, and its raw material and injection have been taken in two ones four of the health ministry drug standard.These article 1970 are by the exploitation listing of French Egic company; Formulation has injection and oral preparation, because it has advantages such as rapid-action, that Plasma Concentration is high, curative effect is obvious, after this other various countries manufacture experimently in succession and produce; But there is the problem of product stability difference in existing DL-Aspisol salt preparation method more; Be prone to decomposite Whitfield's ointment, cause the pungency of medicine and sensitization to increase, thereby the application of DL-Aspisol salt receive certain restriction; Big quantity research has also been carried out to its stability one after another in each pharmaceutical factory, has improved the Sanitation Ministry medicine standard each item index in succession.
At present, DL-Aspisol salt mainly contains following preparation method:
Pharmacy six Zhou Yumei of factory in Chongqing are dissolved in DL-Methionin and Frosst) respectively in an amount of ethanol, hybrid reaction two hours, filter obtain DL-Aspisol salt (Zhou Yumei, Liu Changhua and Wang Shenrong. the preparation of LAS [J]; Chinese Journal of Pharmaceuticals; 1988 02 phases).The inventor studies this method, though productive rate up to 88%, quality product does not conform to the symbol requirement, Frosst) and lysine content are all undesirable, the product Whitfield's ointment also exceeds standard greatly.
Pharmaceutical factory of Ting Bian medical college yellow row iron is dissolved in DL-Methionin and Frosst) respectively in suitable quantity of water and the ethanol; Lysine solution is slowly joined in the Frosst) ethanolic soln; After reacting completely; Add acetone, the crystallization of lowering the temperature simultaneously obtain DL-Aspisol salt (Huang Hangtie, Zhu Changlie and Jin Yingxie. the discussion of LAS ME [J]; Yanbian University's medical journal; 1986 04 phases).The inventor studies this method, and product stability is poor, and the shelf-time is short, and the technological process noxious solvent acetone that needs that much or many, and product has certain acetone residual, and environment is also caused certain pollution.
The patent No. is that national inventing patent that ZL92104036.9, name are called " method of manufacture of LAS " discloses and in 20～40 minutes, evenly joins lysine solution in the Frosst) alcoholic solution; Reaction solution is compared in 65: 35～71: 29 scope at pure water; And then add absolute ethyl alcohol reaction solution alcohol water ratio was increased to 72: 28～90: 10, make LAS through common process such as cooling, insulation, fractional crystallization, vacuum-dryings then.This patent is regulated the speed of response of LAS through the concentration of the pure water of control, but the inventor discovers the preparation poor repeatability to this method.
The national inventing patent application that number of patent application is 200910090263.5, name is called " preparation method of improved LAS " discloses a kind of preparation method of improved LAS; In the pure liquid of Frosst), adding mass percentage concentration under 15～25 ℃ is 25～30% lysine solution, makes Methionin quality and Frosst) mass ratio between 1: 1.3～1: 1.5, stirring and crystallizing 5～15 minutes; 3～4 times of amounts that are incorporated as the Frosst) quality are then separated out alcohol; Lower the temperature in 10 ℃, and stirred growing the grain 0.5～1.5 hour, cross and filter crystal; With an amount of absolute ethanol washing crystal, vacuum-drying obtains LAS.The inventor carries out repetition according to above-mentioned technology to this method, and quality product meets the Sanitation Ministry medicine standard each item index, but in production process, needs to add to separate out alcohol in a large number, and needs to reduce temperature of reaction system, complicated steps, and cost is higher.
Above method all need be used a large amount of alcohol when one-tenth salts out, cause the increase of production cost, and the extra reduction temperature that needs treats that the DL-Aspisol salts out complicated steps.
Summary of the invention
The shortcoming that primary and foremost purpose of the present invention is to overcome prior art provides a kind of preparation method of DL-Aspisol salt with not enough.
Another object of the present invention is to provide the preparing method's of described DL-Aspisol salt application.
The object of the invention is realized through following technical proposals: a kind of preparation method of DL-Aspisol salt comprises following steps:
(1) preparation of DL-lysine solution: with water dissolution DL-Methionin, the final concentration that makes DL-Methionin is that massfraction is 30～35%, and sterile filtration obtains the DL-lysine solution;
(2) preparation of Frosst) organic solution: use the organic solvent dissolution Frosst), the final concentration that makes Frosst) is a massfraction 18～20%, and sterile filtration obtains Frosst) organic solution;
(3) preparation of DL-Aspisol salt: in the Frosst) organic solution of step (2) preparation, add the DL-lysine solution that step (1) prepares, wherein Frosst) and DL-Methionin are pressed mass ratio 1～1.2: 1 proportioning; Stir down and fully reacted 2～4 hours, separate out DL-Methionin and Frosst) salify; After separating out fully, separate obtaining DL-Methionin and Frosst) salify, organic solvent washing, drying obtains DL-Aspisol salt;
Water described in the step (1) is preferably purified water; Described dissolved temperature is preferably room temperature;
The final concentration of the DL-Methionin described in the step (1) more preferably massfraction is 31.8～35%;
It is the membrane filtration of 0.22 μ m that the aperture is preferably used in sterile filtration described in the step (1);
Organic solvent described in the step (2) comprises absolute ethyl alcohol, anhydrous methanol and acetone; Described dissolved temperature is preferably room temperature;
The final concentration of the Frosst) described in the step (2) is massfraction 18.92～19.68% more preferably;
It is the membrane filtration of 0.22 μ m that the aperture is preferably used in sterile filtration described in the step (2);
Frosst) described in the step (3) and described DL-Methionin are more preferably pressed mass ratio 1～1.16: 1 proportioning;
Organic solvent described in the step (3) comprises absolute ethyl alcohol, anhydrous methanol and acetone;
Exsiccant mode described in the step (3) is preferably vacuum-drying;
Described vacuum drying condition optimization is 40～60 ℃ of dryings 4～8 hours;
The acid number of the DL-Aspisol salt described in the step (3) is below 6, and free salicylic acid is below 0.3%, and the DL-lysine content is a mass percent 43.9～45.7%, and aspirin content is a mass percent 54.1～56.3%;
The application of the preparation method of described DL-Aspisol salt in scale operation DL-Aspisol salt.
The present invention has following advantage and effect with respect to prior art:
(1) preparing method's production cost provided by the present invention is low, and step is simple: the technological process consumption of organic solvent seldom need not reduce temperature of reaction system, thereby greatly reduces production cost.
(2) the product yield high (more than 80%) that obtains through preparation method of the present invention; Quality is high, and (the product acid number is below 6; Free salicylic acid is below 0.3%, and the DL-lysine content is a mass percent 43.9～45.7%, and aspirin content is a mass percent 54.1～56.3%); Good stability; Frosst)=1: 1～1: 1.2), the control of moisture content in the reaction system each item index all reaches the Sanitation Ministry medicine standard, and (the Methionin:, make crux index free salicylic acid and acidity be higher than the Sanitation Ministry medicine standard far away of the feed ratio through changing material.
Description of drawings
Fig. 1 is a preparing method's of the present invention process flow sheet.
Embodiment
Below in conjunction with embodiment and accompanying drawing the present invention is described in further detail, but embodiment of the present invention is not limited thereto.
Embodiment 1
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 8.4kg and add retort; Add water 16.8kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 33.3%; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic DL-lysine solution;
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 9.6kg and add retort; Add the 40kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 19.35%wt; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1.14) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 3 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 40 ℃ of vacuum-dryings obtained DL-Aspisol salt 15.2kg, yield 84.4% in 4 hours.
Products obtained therefrom is through detecting (the pharmaceutical chemicals terrestrial reference rises 16 WS1-XG-015-2001Z of GB) Frosst) 55.2%wt, Methionin 44.7%wt, acid number: pH=5.6, free salicylic acid 0.2%.Quality product is higher than the Sanitation Ministry medicine standard far away.
Products obtained therefrom detects the back with packing, put in storage through the wrapping material that clean, sterilization is good.
Embodiment 2
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 8.4kg and add retort; Add water 15.6kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 35%; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic DL-lysine solution;
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 9.8kg and add retort; Add the 42kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 18.92%wt; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1.16) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 2 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 50 ℃ of vacuum-dryings obtained DL-Aspisol salt 15.5kg, yield 85.2% in 6 hours.
Products obtained therefrom is through detecting: Frosst) 55.4%wt, Methionin 44.2%wt, acid number: pH=5.8, free salicylic acid 0.2%.Quality product is higher than the Sanitation Ministry medicine standard far away.
Products obtained therefrom detects the back with packing, put in storage through the wrapping material that clean, sterilization is good.
Embodiment 3
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 9.8kg and add retort; Add water 21kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 31.8%; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic DL-lysine solution;
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 9.8kg and add retort; Add the 40kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 19.68%wt; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 60 ℃ of vacuum-dryings obtained DL-Aspisol salt 17.5kg, yield 89.3% in 5 hours.
Products obtained therefrom is through detecting: Frosst) 55.4%wt, Methionin 45.2%wt, acid number: pH=5.7, free salicylic acid 0.2%.Quality product is higher than the Sanitation Ministry medicine standard far away.
Products obtained therefrom detects the back with packing, put in storage through the wrapping material that clean, sterilization is good.
Embodiment 4
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 9.8kg and add retort; Add water 21kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 31.8%; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic DL-lysine solution;
(2) preparation of Frosst) methanol solution: take by weighing Frosst) 9.8kg and add retort; Add the 40kg anhydrous methanol then, stirring and dissolving, the final concentration of Frosst) is 19.68%wt; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic Frosst) methanol solution;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1) in the disposable Frosst) methanol solution that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, with a small amount of anhydrous methanol washing, 40 ℃ of vacuum-dryings obtained DL-Aspisol salt 16.5kg, yield 84.2% in 8 hours.
Products obtained therefrom is through detecting: Frosst) 54.8%wt, Methionin 44.9%wt, acid number: pH=5.7, free salicylic acid 0.2%.Quality product is higher than the Sanitation Ministry medicine standard far away.
Products obtained therefrom detects the back with packing, put in storage through the wrapping material that clean, sterilization is good.
Embodiment 5
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 8.5kg and add retort; Add water 16.8kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 33.6%; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic DL-lysine solution;
(2) preparation of Frosst) acetone soln: take by weighing Frosst) 9.5kg and add retort; Add 40kg acetone then, stirring and dissolving, the final concentration of Frosst) is 19.19%wt; Using the aperture is the membrane filtration of 0.22 μ m, obtains aseptic Frosst) acetone soln;
(3) preparation of DL-Aspisol salt: the DL-lysine solution of step (1) preparation is joined fast (DL-Methionin and Frosst) mass ratio are (1: 1.14) in the Frosst) acetone soln of step (2) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, with the small amount of acetone washing, 50 ℃ of vacuum-dryings obtained DL-Aspisol salt 14.7kg, yield 81.6% in 4 hours.
Products obtained therefrom is through detecting: Frosst) 55.4%wt, Methionin 45.2%wt, acid number: pH=5.5, free salicylic acid 0.2%.Quality product is higher than the Sanitation Ministry medicine standard far away.
Products obtained therefrom detects the back with packing, put in storage through the wrapping material that clean, sterilization is good.
The comparative example 1
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution:, obtain the DL-lysine solution with embodiment 3 steps (1);
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 9.5kg and add retort, add the 40kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 19.19%wt, sterile filtration obtains the Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 0.97) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 40 ℃ of vacuum-dryings obtained DL-Aspisol salt 16.2kg, yield 83.9% in 8 hours.
Products obtained therefrom is through detecting: Frosst) 53.5%wt, Methionin 45.6%wt, acid number: pH=6.5, free salicylic acid 0.3%.Excessive because of DL-Methionin in the reaction system, cause in the product aspirin content on the low side, in standard value 54.1～56.3%, quality product is not defective for content.
The comparative example 2
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 9.8kg and add retort, add water 22kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 30.8%, sterile filtration (0.22 μ m) obtains the DL-lysine solution;
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 12.45kg and add retort, add the 50kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 19.94%wt, sterile filtration obtains the Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1.27) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 60 ℃ of vacuum-dryings obtained DL-Aspisol salt 18.2kg, yield 81.8% in 6 hours.
Products obtained therefrom is through detecting: Frosst) 55.5%wt, Methionin 43.3%wt, acid number: pH=5.5, free salicylic acid 0.4%.Excessive because of Frosst) in the reaction system, the content that causes Frosst) is not in standard value 54.1～56.3%, and also not in standard value 43.9%-45.7%, quality product is defective for the DL-lysine content.
The comparative example 3
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 9.8kg and add retort, add water 25kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 28.16%, sterile filtration obtains the DL-lysine solution;
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 9.8kg and add retort, add the 40kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 19.68%wt, sterile filtration obtains the Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 50 ℃ of vacuum-dryings obtained DL-Aspisol salt 14.2kg, yield 72.45% in 7 hours.
Products obtained therefrom is through detecting: Frosst) 54.5%wt, Methionin 45.3%wt, acid number: pH=6.6, free salicylic acid 0.6%.Because of DL-lysine solution concentration is 28.16%, products obtained therefrom pH value exceeds standard, and quality product is defective, and the percentage composition of reaction system water is high, and product yield is lower.
The comparative example 4
Preparation DL-Aspisol salt, as shown in Figure 1.
(1) preparation of DL-lysine solution: take by weighing DL-Methionin 9.8kg and add retort, add water 17kg then, stirring and dissolving, the final concentration of DL-Methionin is that massfraction is 36.57%, sterile filtration obtains the DL-lysine solution;
(2) preparation of Frosst) ethanolic soln: take by weighing Frosst) 9.8kg and add retort, add the 40kg absolute ethyl alcohol then, stirring and dissolving, the final concentration of Frosst) is 19.68%wt, sterile filtration obtains the Frosst) ethanolic soln;
(3) preparation of DL-Aspisol salt: with (DL-Methionin and Frosst) mass ratio are (1: 1) in the disposable Frosst) ethanolic soln that joins step (2) preparation of the DL-lysine solution of step (1) preparation; Stirring reaction 4 hours is separated out DL-Methionin and Frosst) salify.Wait to separate out complete after-filtration separation and obtain DL-Methionin and Frosst) salify, use a small amount of absolute ethanol washing, 50 ℃ of vacuum-dryings obtained DL-Aspisol salt 17.2kg, yield 87.76% in 8 hours
Products obtained therefrom is through detecting: Frosst) 54.5%wt, Methionin 44.3%wt, acid number: pH=5.6, free salicylic acid 1.0%.Because of DL-lysine solution concentration is 36.57%, the products obtained therefrom free salicylic acid exceeds standard, and product is defective.
The foregoing description is a preferred implementation of the present invention; But embodiment of the present invention is not restricted to the described embodiments; Other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; All should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (10)
1. the preparation method of a DL-Aspisol salt is characterized in that comprising following steps:
(1) preparation of DL-lysine solution: with water dissolution DL-Methionin, the final concentration that makes DL-Methionin is that massfraction is 30～35%, and sterile filtration obtains the DL-lysine solution;
(2) preparation of Frosst) organic solution: use the organic solvent dissolution Frosst), the final concentration that makes Frosst) is a massfraction 18～20%, and sterile filtration obtains Frosst) organic solution;
(3) preparation of DL-Aspisol salt: in the Frosst) organic solution of step (2) preparation, add the DL-lysine solution that step (1) prepares, wherein Frosst) and DL-Methionin are pressed mass ratio 1～1.2: 1 proportioning; Stir down and fully reacted 2～4 hours, separate out DL-Methionin and Frosst) salify; After separating out fully, separate obtaining DL-Methionin and Frosst) salify, organic solvent washing, drying obtains DL-Aspisol salt.
2. the preparation method of DL-Aspisol salt according to claim 1 is characterized in that: the water described in the step (1) is purified water.
3. the preparation method of DL-Aspisol salt according to claim 1 is characterized in that: the sterile filtration described in step (1) and the step (2) is the membrane filtration of 0.22 μ m for using the aperture.
4. the preparation method of DL-Aspisol salt according to claim 1 is characterized in that: the organic solvent described in step (2) and (3) is one or both in alcohol or the ketone.
5. the preparation method of DL-Aspisol salt according to claim 4 is characterized in that: described alcohol is absolute ethyl alcohol or anhydrous methanol; Described ketone is acetone.
6. the preparation method of DL-Aspisol salt according to claim 1 is characterized in that: Frosst) described in the step (3) and described DL-Methionin are pressed mass ratio 1～1.16: 1 proportioning.
7. the preparation method of DL-Aspisol salt according to claim 1 is characterized in that: the exsiccant mode described in the step (3) is vacuum-drying.
8. the preparation method of DL-Aspisol salt according to claim 7 is characterized in that: described vacuum drying condition is 40～60 ℃ of dryings 4～8 hours.
9. the preparation method of DL-Aspisol salt according to claim 1; It is characterized in that: the acid number of the DL-Aspisol salt described in the step (3) is below 6; Free salicylic acid is below 0.3%; The DL-lysine content is a mass percent 43.9～45.7%, and aspirin content is a mass percent 54.1～56.3%.
10. the application of the preparation method of each described DL-Aspisol salt of claim 1～9 in scale operation DL-Aspisol salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102964578A CN102503845A (en) | 2011-09-28 | 2011-09-28 | Preparation method of DL-lysine aspirin salt and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102964578A CN102503845A (en) | 2011-09-28 | 2011-09-28 | Preparation method of DL-lysine aspirin salt and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102503845A true CN102503845A (en) | 2012-06-20 |
Family
ID=46215996
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102964578A Pending CN102503845A (en) | 2011-09-28 | 2011-09-28 | Preparation method of DL-lysine aspirin salt and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102503845A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20121144A1 (en) * | 2012-06-28 | 2013-12-29 | Dipharma Francis Srl | PROCEDURE FOR THE PREPARATION OF A SALT OF A NON STEROIDOUS ANTI-INFLAMMATORY MEDICINE |
| CN104744249A (en) * | 2013-12-31 | 2015-07-01 | 海口天行健药物研究有限公司 | Method for preparing stable salt of aspirin and alkaline amino acid |
| WO2015181304A1 (en) * | 2014-05-28 | 2015-12-03 | Unither Pharmaceuticals | Method for preparing a salt of acetylsalicylic acid and a basic amino acid |
| CN106674036A (en) * | 2016-12-22 | 2017-05-17 | 河南中医学院 | Method for synthesizing aspirin-dl-lysine through non-organic solvent method |
| CN110114333A (en) * | 2016-12-23 | 2019-08-09 | 文塔里昂有限责任公司 | The improvement of lysine acetylsalicylate salt glycine particle synthesizes |
| CN110511156A (en) * | 2019-08-28 | 2019-11-29 | 广州普星药业有限公司 | A kind of preparation method of di-lysine-aspirin |
| CN112500306A (en) * | 2020-12-11 | 2021-03-16 | 佛山普正医药科技有限公司 | Synthesis method of aspirin-lysine |
| CN114478287A (en) * | 2021-12-31 | 2022-05-13 | 蚌埠丰原医药科技发展有限公司 | Aspirin-lysine crystal form, preparation method and application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1078888A (en) * | 1992-05-22 | 1993-12-01 | 蚌埠市医药研究所实验药厂 | The manufacture method of aspisol |
| CN1468209A (en) * | 2000-07-18 | 2004-01-14 | Stable salts of o-acetylsalicyclic with basic amino acids | |
| CN101248036A (en) * | 2005-06-02 | 2008-08-20 | 拜耳医药保健股份公司 | Stabile active ingredient complex of salts of the o-acetylsalicylic acid with basic amino acids and glycine |
| CN101633624A (en) * | 2009-08-04 | 2010-01-27 | 蚌埠丰原医药科技发展有限公司 | Preparation method of improved di-lysine-aspirin |
-
2011
- 2011-09-28 CN CN2011102964578A patent/CN102503845A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1078888A (en) * | 1992-05-22 | 1993-12-01 | 蚌埠市医药研究所实验药厂 | The manufacture method of aspisol |
| CN1468209A (en) * | 2000-07-18 | 2004-01-14 | Stable salts of o-acetylsalicyclic with basic amino acids | |
| CN101248036A (en) * | 2005-06-02 | 2008-08-20 | 拜耳医药保健股份公司 | Stabile active ingredient complex of salts of the o-acetylsalicylic acid with basic amino acids and glycine |
| CN101633624A (en) * | 2009-08-04 | 2010-01-27 | 蚌埠丰原医药科技发展有限公司 | Preparation method of improved di-lysine-aspirin |
Non-Patent Citations (2)
| Title |
|---|
| 周玉梅等: "赖氨匹林的制备", 《医药工业》 * |
| 黄行铁: "赖氨匹林制造工艺的探讨", 《延边医学院学报》 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20121144A1 (en) * | 2012-06-28 | 2013-12-29 | Dipharma Francis Srl | PROCEDURE FOR THE PREPARATION OF A SALT OF A NON STEROIDOUS ANTI-INFLAMMATORY MEDICINE |
| CN104744249A (en) * | 2013-12-31 | 2015-07-01 | 海口天行健药物研究有限公司 | Method for preparing stable salt of aspirin and alkaline amino acid |
| WO2015181304A1 (en) * | 2014-05-28 | 2015-12-03 | Unither Pharmaceuticals | Method for preparing a salt of acetylsalicylic acid and a basic amino acid |
| FR3021654A1 (en) * | 2014-05-28 | 2015-12-04 | Unither Pharmaceuticals | PROCESS FOR THE PREPARATION OF AN ACETYLSALICYLIC ACID SALT AND A BASIC AMINO ACID |
| US9745246B2 (en) | 2014-05-28 | 2017-08-29 | Unither Pharmaceuticals | Method for preparing a salt of acetylsalicylic acid and a basic amino acid |
| CN106674036A (en) * | 2016-12-22 | 2017-05-17 | 河南中医学院 | Method for synthesizing aspirin-dl-lysine through non-organic solvent method |
| CN106674036B (en) * | 2016-12-22 | 2018-08-14 | 河南中医学院 | The method that non-organic solvent method synthesizes di-lysine-aspirin |
| CN110114333A (en) * | 2016-12-23 | 2019-08-09 | 文塔里昂有限责任公司 | The improvement of lysine acetylsalicylate salt glycine particle synthesizes |
| CN110511156A (en) * | 2019-08-28 | 2019-11-29 | 广州普星药业有限公司 | A kind of preparation method of di-lysine-aspirin |
| CN110511156B (en) * | 2019-08-28 | 2023-04-07 | 广州普星药业有限公司 | Preparation method of aspirin-lysine |
| CN112500306A (en) * | 2020-12-11 | 2021-03-16 | 佛山普正医药科技有限公司 | Synthesis method of aspirin-lysine |
| CN114478287A (en) * | 2021-12-31 | 2022-05-13 | 蚌埠丰原医药科技发展有限公司 | Aspirin-lysine crystal form, preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102503845A (en) | Preparation method of DL-lysine aspirin salt and application thereof | |
| CN104072549B (en) | The production technique of Gastrodine | |
| CN102659818A (en) | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound | |
| CN102924483A (en) | Ceftazidime crystal compound, preparation method of compound and pharmaceutical composition of compound in sterile mixed powder form | |
| CN102079737B (en) | Method for preparing apigenin | |
| CN102286041A (en) | Method for purifying stevioside by recrystallization | |
| CN102351795A (en) | Edaravone compound with stable crystal form | |
| CN103896930B (en) | The preparation method of canagliflozin semihydrate medicinal crystal-form | |
| CN102731523B (en) | Preparation method of beta-artemether | |
| CN102101661B (en) | Method for preparing high-purity monopotassium phosphate crude medicine | |
| CN102391128B (en) | Production method of antibiotic pharmaceutical intermediate mono-p-nitro benzyl malonate | |
| CN103739638A (en) | Method for purifying tea saponin through microbial fermentation | |
| CN104557576A (en) | Method for preparing high-purity pregabalin | |
| CN101781264B (en) | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole | |
| CN101863818B (en) | Method for preparing DL-proline | |
| CN109096129A (en) | A kind of preparation method of L-carnitine-L-tartrate | |
| CN107879979A (en) | A kind of preparation method of Dexmedetomidine | |
| CN102351775B (en) | Preparation method of levo-5-hydroxytryptophan | |
| CN105461718A (en) | 5-Bromo-7-azaindole synthesis process | |
| CN105566296A (en) | Method for preparing dabigatran amidated impurities | |
| CN102603596B (en) | Preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide | |
| CN102206185B (en) | Process for refining bendazac lysine and analogs thereof | |
| CN101817796A (en) | Method for preparing cefotiam side chain | |
| CN105693793A (en) | Ribavirin compound and drug composition of ribavirin compound | |
| CN105418507A (en) | Preparation method for 1-(3-methyl-1-phenyl-1H-pyrazole-5-yl)piperazine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120620 |