CN104693029A - A preparing method of arginine aspirin sterile powder - Google Patents
A preparing method of arginine aspirin sterile powder Download PDFInfo
- Publication number
- CN104693029A CN104693029A CN201310655447.8A CN201310655447A CN104693029A CN 104693029 A CN104693029 A CN 104693029A CN 201310655447 A CN201310655447 A CN 201310655447A CN 104693029 A CN104693029 A CN 104693029A
- Authority
- CN
- China
- Prior art keywords
- arginine
- dehydrated alcohol
- aspirin
- press filtration
- crystal seed
- 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.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparing method of arginine aspirin sterile powder. The method includes following steps of: reacting absolute ethyl alcohol, aspirin, arginine and water, performing filter pressing, adding a crystal seed, adding absolute ethyl alcohol, cooling, washing and drying. The method is an improvement based on a scheme provided by the prior art, and is compact in crystallization temperature-maintaining time and total preparation time, thus further reducing production of free salicylic acid in a process.
Description
Technical field
The present invention relates to the preparation method of Aspirin-arginine, be specifically related to a kind of preparation method of Aspirin-arginine aseptic powder.
Background technology
Aspirin-arginine (Arginine Aspirin) is the double salt that L-arginine and acetylsalicylic acid are formed, and also claim Aspirin-arginin, its pharmacological action is identical with acetylsalicylic acid, for generating heat and the symptomatic treatment of light moderate pain.Because it is good water-soluble, can make injection, for intramuscular injection or quiet note, onset is relatively fast and strong.
Existing preparation method and shortcoming:
Aspirin-arginine normally reacts when 30-40 DEG C with the alcoholic solution of the arginic aqueous solution and acetylsalicylic acid, and add distilled water and solution is clarified, sterile filtration, the mode of then crystallization, filtration obtains.But this method amount of water is relatively high, possibility crystallize out hardly, so there is report to need to adopt freeze-drying.
Another kind method is as patent CN200910210671.X(CN101704766A) be that arginine is directly added in the alcoholic solution of acetylsalicylic acid, then add a small amount of water, stirring and dissolving, utilize the timing window being dissolved into precipitation to complete sterile filtration.But there are some problems in this method: 1. arginine powder thickness is uneven, containing particle more than 30-50%40 order, dissolution time is longer, arginine is occurred not dissolve completely and Aspirin-arginine has started the phenomenon separated out, the window phase filtered is short or do not have, and cannot complete Sterile Filtration.2. amount of water is slightly large, though the filter window phase is long, following processes cannot be separated out; Add water few, dissolve slow, then the filter window phase is short or do not have, and filters midway and already separates out Aspirin-arginine crystal, blocking filter.3., in the aseptic crystallization still of high-cleanness, high without dust, Aspirin-arginine almost can not be separated out in sporadic nucleation.
Common Aspirin-arginine preparation method adopts lyophilize as CN201110028957.3 (publication number is CN102146030A), pressed powder can be obtained, but compared with the method for crystallization in the solution, in its process, degraded product cannot be removed, free salicylic acid is higher, freeze-drying prods water content is general also comparatively large, and stability has problem.
Although the method for described patent is novel, in lab scale, easily obtain non-sterile product, still can not in large production, solve filter window phase problem and sporadic nucleation crystallization can not be realized, therefore cannot prepare sterile product.
Therefore, need a kind ofly avoid degrading and increase the method for the Aspirin-arginine of yield.
Summary of the invention
The object of the invention is on the basis of existing technology, control arginic granularity, dissolution time is shortened, dissolve clarification boundary obviously, the filter window phase is easy to grasp.
The preparation method of a kind of Aspirin-arginine aseptic powder provided by the invention, the method comprises the following steps: dehydrated alcohol, acetylsalicylic acid, arginine and water react, and press filtration, adds crystal seed, adds dehydrated alcohol, cooling, and washing is dry, to obtain final product.
Concrete, the method comprises the following steps:
1) dehydrated alcohol, acetylsalicylic acid, arginine and water are mixed, stirring and dissolving, control temperature 15-25 DEG C, until solution clarification, rapidly through 0.22 μm of filter press filtration, in pressure-filtering process, add crystal seed, adjustment filtrate temperature is to 25-35 DEG C, and press filtration terminates, and continues insulation crystallization 1-4 hour;
2) in the liquid after step 1) crystallization, add the dehydrated alcohol with liquid aliquot, be then cooled to about 5 DEG C with the speed of 10 DEG C/h, insulation 3-9 hour;
3) rejection filter, absolute ethanol washing 2 times, 35-40 DEG C of vacuum-drying 8-10 hour.
Preferably, the method comprises the following steps:
1) dehydrated alcohol, acetylsalicylic acid, arginine and water are mixed, stirring and dissolving, control temperature 18-20 DEG C, until solution clarification, rapidly through 0.22 μm of filter press filtration, start to add crystal seed between end in press filtration, add the 0.05-5% that crystal seed amount is Aspirin-arginine theoretical amount, adjustment filtrate temperature is to 28-30 DEG C, and press filtration terminates, and continues insulation crystallization 2-3 hour;
2) in the liquid after step 1) crystallization, add the dehydrated alcohol with liquid aliquot, be then cooled to about 5 DEG C with the speed of 10 DEG C/h, insulation 5-7 hour;
3) rejection filter, absolute ethanol washing 2 times, 35-40 DEG C of vacuum-drying 8-10 hour.
In aforesaid method:
The weight ratio of described acetylsalicylic acid, arginine, dehydrated alcohol and water is 1.03: 1: 5-20: 0.1-1, and weight ratio is preferably 1.03: 1: 5-10: 0.4-0.8;
Described arginic size range 60-120 order, best 80-100 order;
Step 1) adds opportunity of crystal seed and mode starts disposable between end adding in press filtration;
Step 1) adds the 0.9-5% that crystal seed amount is Aspirin-arginine theoretical amount;
In step 2) in the dehydrated alcohol added, improve ethanol content.
The preparation method of Aspirin-arginine provided by the invention has the following advantages:
1, method is resolved:
(1) in the present invention, arginine is ground into 80-100 order in advance, through 15-25 DEG C of dissolving, as long as namely 5-10 minute can dissolve clarification, by controlling arginic granularity, dissolution time is shortened, and dissolves clarification boundary obviously, and the filter window phase is easy to grasp.
(2) dissolve arginine speed in the present invention fast, thus lower temperature 15-25 DEG C can be adopted, so the filter window phase can reach 1-1.5 hour, be enough to Sterile Filtration; Because at a higher temperature as 30-40 DEG C, dissolve fast, separate out also fast, the filter window phase narrows on the contrary.
(3) the present invention adopts the method adding crystal seed, and achieving and separate out Aspirin-arginine crystal in the aseptic crystallization still of high-cleanness, high without dust, is the method that induced crystal is separated out rapidly.
(4) the present invention passes through the selection adding crystal seed opportunity and add-on, and achieve high yield crystallization, yield reaches more than 80%.
2, the object of the invention is the optimization on the scheme basis that provides in prior art, crystallization soaking time, overall preparation time is compact, produces free salicylic acid in further minimizing process.
Embodiment
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.
Embodiment 1: the preparation method of Aspirin-arginine aseptic powder
1) in 200 liters of dissolution kettle, add dehydrated alcohol 100kg, acetylsalicylic acid 10.3kg, arginine (granularity is 80 orders) 10kg and water 4kg, control temperature 18-20 DEG C, stirring and dissolving, solution clarification in about 10 minutes, then crystallization kettle is risen through 0.22 μm of filter press filtration to 300 rapidly, in pressure-filtering process, in crystallization kettle, add that crystal seed 20g(adds that crystal seed amount is Aspirin-arginine theoretical amount 0.99%), the temperature of adjustment crystallization kettle is to 28-30 DEG C, press filtration terminates, and continues insulation crystallization 2 hours;
2) in the liquid after step 1) crystallization, add dehydrated alcohol 100kg, be then cooled to about 5 DEG C with 10 DEG C/h, be incubated 6 hours;
3) rejection filter, absolute ethanol washing 2 times, the consumption of each dehydrated alcohol is 20kg/ time, 35-36 DEG C of vacuum-drying 10 hours.
Embodiment 2: the preparation method of Aspirin-arginine aseptic powder
1) in 200 liters of dissolution kettle, add dehydrated alcohol 80kg, acetylsalicylic acid 10.3kg, arginine (granularity is 100 orders) 10kg and water 6kg, control temperature 18-20 DEG C, stirring and dissolving, solution clarification in about 10 minutes, then crystallization kettle is risen through 0.22 μm of filter press filtration to 300 rapidly, in pressure-filtering process, in crystallization kettle, add that crystal seed 60g(adds that crystal seed amount is Aspirin-arginine theoretical amount 2.96%), the temperature of adjustment crystallization kettle is to 28-30 DEG C, press filtration terminates, and continues insulation crystallization 2 hours;
2) in the liquid after step 1) crystallization, add dehydrated alcohol 80kg, be then cooled to about 5 DEG C with 10 DEG C/h, be incubated 6 hours;
3) rejection filter, absolute ethanol washing 2 times, the consumption of dehydrated alcohol is 20kg/ time, 36-38 DEG C of vacuum-drying 8 hours.
Embodiment 3: the preparation method of Aspirin-arginine aseptic powder
1) in 200 liters of dissolution kettle, add dehydrated alcohol 50kg, acetylsalicylic acid 10.3kg, arginine (granularity is 120 orders) 10kg and water 8kg, control temperature 18-20 DEG C, stirring and dissolving, the clarification of about 10 minutes solution, rises crystallization kettle through 0.22 μm of filter press filtration to 300 rapidly, and in pressure-filtering process, in crystallization kettle, add that crystal seed 100g(adds that crystal seed amount is Aspirin-arginine theoretical amount 4.93%), adjustment crystallization kettle temperature is to 28-30 DEG C, press filtration terminates, and continues insulation crystallization 2 hours
2) in the liquid after step 1) crystallization, add dehydrated alcohol 50kg, be then cooled to about 5 DEG C with 10 DEG C/h, be incubated 6 hours;
3) rejection filter, absolute ethanol washing 2 times, the consumption of dehydrated alcohol is 20kg/ time, 38-40 DEG C of vacuum-drying 8 hours.
Comparative example 1:
With reference to CN200910210671.X(CN101704766A) embodiment 2, belong to the method that in this patent, free salicylic acid (0.25%) is minimum.
Comparative example 2:
With reference to the embodiment 3 of CN201110028957.3 (publication number is CN102146030A), belong to the method for free salicylic acid minimum (0.12%).
Experimental example 1: the comparison of yield and purity
To embodiment 1-3 and the yield of comparative example 1,2, the comparison of purity aspect, the detection method of its moderate purity is specially:
Purity adopts chemical analysis method, namely degradation production is detected---free salicylic acid: get this product 10mg, adding acetum (0.4 → 100) makes dissolving make 50ml, the dilute sulphuric acid iron ammonium solution adding brand-new immediately [gets hydrochloric acid (1mol/L) 1ml, add ferric ammonium sulfate indicating liquid 2ml, adding water to 100ml] 1ml shakes up, as colour developing in 30 seconds, [precision takes Whitfield's ointment 100mg with contrasting liquid, add a small amount of dissolve with ethanol, add acetum (0.4 → 100) and make into 1000ml, shake up, get 0.1ml(or 0.2ml, 0.3ml etc.), add acetum (0.4 → 100) to 50ml, add brand-new dilute sulphuric acid iron ammonia solution 1ml] compare, limit is 0.1%(or 0.2%, 0.3% etc.).
Yield, purity and aseptic detected result: in table 1
Table 1: the comparison of yield and purity
| Yield % | Purity % | |
| Embodiment 1 | 87.3 | <0.1 |
| Embodiment 2 | 86.5 | <0.1 |
| Embodiment 3 | 86.8 | <0.1 |
| Comparative example 1 | 77.0 | 0.25 |
| Comparative example 2 | 82.0 | 0.12 |
Table 1 result shows, and the yield of embodiment 1-3 is 86-88%, and purity is that <0.1%(is in degradation production free salicylic acid), be all better than the value of comparative example.
Result shows: the preparation method that this aspect provides obviously is better than prior art in yield and purity.
Although above with general explanation, embodiment and test, the present invention is described in detail, and on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Claims (8)
1. a preparation method for Aspirin-arginine aseptic powder, is characterized in that, the method comprises the following steps: dehydrated alcohol, acetylsalicylic acid, arginine and water react, and press filtration, adds crystal seed, adds dehydrated alcohol, cooling, and washing is dry, to obtain final product.
2. method according to claim 1, is characterized in that, the method comprises the following steps:
1) dehydrated alcohol, acetylsalicylic acid, arginine and water are mixed, stirring and dissolving, control temperature 15-25 DEG C, until solution clarification, rapidly through 0.22 μm of filter press filtration, in pressure-filtering process, add crystal seed, adjustment filtrate temperature is to 25-35 DEG C, and press filtration terminates, and continues insulation crystallization 1-4 hour;
2) in the liquid after step 1) crystallization, add the dehydrated alcohol with liquid aliquot, be then cooled to about 5 DEG C with the speed of 10 DEG C/h, insulation 3-9 hour;
3) rejection filter, absolute ethanol washing 2 times, 35-40 DEG C of vacuum-drying 8-10 hour.
3. method according to claim 1, is characterized in that, the method comprises the following steps:
1) dehydrated alcohol, acetylsalicylic acid, arginine and water are mixed, stirring and dissolving, control temperature 18-20 DEG C, until solution clarification, rapidly through 0.22 μm of filter press filtration, start to add crystal seed between end in press filtration, add the 0.05-5% that crystal seed amount is Aspirin-arginine theoretical amount, adjustment filtrate temperature is to 28-30 DEG C, and press filtration terminates, and continues insulation crystallization 2-3 hour;
2) in the liquid after step 1) crystallization, add the dehydrated alcohol with liquid aliquot, be then cooled to about 5 DEG C with the speed of 10 DEG C/h, insulation 3-9 hour;
3) rejection filter, absolute ethanol washing 2 times, 35-40 DEG C of vacuum-drying 8-10 hour.
4. the method according to any one of claim 1-3, is characterized in that, the weight ratio of described acetylsalicylic acid, arginine, dehydrated alcohol and water is 1.03: 1: 5-20: 0.1-1.
5. method according to claim 4, is characterized in that, the weight ratio of described acetylsalicylic acid, arginine, dehydrated alcohol and water is 1.03: 1: 5-10: 0.4-0.8.
6. the method according to any one of claim 1-3, is characterized in that, described arginic size range 60-120 order, best 80-100 order.
7. the method according to any one of claim 1-3, is characterized in that, step 1) adds opportunity of crystal seed and mode starts disposable between end adding in press filtration.
8. the method according to any one of claim 1-3, is characterized in that, step 1) adds the 0.9-5% that crystal seed amount is Aspirin-arginine theoretical amount.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310655447.8A CN104693029B (en) | 2013-12-05 | 2013-12-05 | A kind of preparation method of Aspirin-arginine aseptic powder |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310655447.8A CN104693029B (en) | 2013-12-05 | 2013-12-05 | A kind of preparation method of Aspirin-arginine aseptic powder |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104693029A true CN104693029A (en) | 2015-06-10 |
| CN104693029B CN104693029B (en) | 2016-06-08 |
Family
ID=53340628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310655447.8A Active CN104693029B (en) | 2013-12-05 | 2013-12-05 | A kind of preparation method of Aspirin-arginine aseptic powder |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104693029B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109559589A (en) * | 2019-01-24 | 2019-04-02 | 河南莱帕克物联装备技术股份有限公司 | A kind of modularization teaching of aspirin production line practices device |
| CN111202842A (en) * | 2020-02-10 | 2020-05-29 | 刘怡 | Pharmaceutical composition for treating hyaluronic acid vascular embolism |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101380329A (en) * | 2008-10-29 | 2009-03-11 | 海南本创医药科技有限公司 | Preparation method of arginine aspirin and powder and injection preparation thereof |
| CN101486644A (en) * | 2009-02-24 | 2009-07-22 | 合肥工业大学 | Preparation of arginine acetylsalicylate |
| CN101704766A (en) * | 2009-11-05 | 2010-05-12 | 蚌埠丰原涂山制药有限公司 | Preparation method of arginine aspirin and powder-injection of arginine aspirin |
| CN102146030A (en) * | 2011-01-26 | 2011-08-10 | 蚌埠丰原医药科技发展有限公司 | Method for preparing argine asprine |
-
2013
- 2013-12-05 CN CN201310655447.8A patent/CN104693029B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101380329A (en) * | 2008-10-29 | 2009-03-11 | 海南本创医药科技有限公司 | Preparation method of arginine aspirin and powder and injection preparation thereof |
| CN101486644A (en) * | 2009-02-24 | 2009-07-22 | 合肥工业大学 | Preparation of arginine acetylsalicylate |
| CN101704766A (en) * | 2009-11-05 | 2010-05-12 | 蚌埠丰原涂山制药有限公司 | Preparation method of arginine aspirin and powder-injection of arginine aspirin |
| CN102146030A (en) * | 2011-01-26 | 2011-08-10 | 蚌埠丰原医药科技发展有限公司 | Method for preparing argine asprine |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109559589A (en) * | 2019-01-24 | 2019-04-02 | 河南莱帕克物联装备技术股份有限公司 | A kind of modularization teaching of aspirin production line practices device |
| CN111202842A (en) * | 2020-02-10 | 2020-05-29 | 刘怡 | Pharmaceutical composition for treating hyaluronic acid vascular embolism |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104693029B (en) | 2016-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20130060049A1 (en) | Method for preparing (s)-4-hydroxy-2-oxo-1-pyrrolidine acetamide | |
| CN101704766B (en) | Preparation method of arginine aspirin and powder-injection of arginine aspirin | |
| CN101874016B (en) | Manufacturing method of 2-hydroxy-5-phenylalkylaminobenzoic acid derivatives and their salts | |
| CN104693029A (en) | A preparing method of arginine aspirin sterile powder | |
| US20120095260A1 (en) | Process for preparation of L-Arginine alpha-ketoglutarate 1:1 and 2:1 | |
| CN103304401A (en) | Preparation method of ibuprofen arginine salt with ultrahigh purity | |
| CN103381359B (en) | Preparation method for catalyst for N,N-dimethyl-caprylamide/decanamide | |
| CN104447758A (en) | Synthesis process of pyrazolo[3,4-d]pyrimidine compounds | |
| CN107445797A (en) | A kind of inexpensive low dangerous synthetic method of cyclopropyl-carbinol | |
| CN108892641B (en) | Preparation method of lappaconitine hydrobromide | |
| CN111285854B (en) | Preparation method of fludioxonil | |
| CN102731340A (en) | Preparation method of demethyl aureomycin hydrochloride | |
| CN100500645C (en) | Purification and production methods of 1-aminocyclopropanecarboxylic acid | |
| CN110003045B (en) | Preparation method of alizarin yellow R sodium salt | |
| CN112851554A (en) | Preparation method of guanidine nitrate | |
| CN103664758B (en) | The synthetic method of Mexidole | |
| CN110642723A (en) | Synthesis method of p-nitro-o-toluidine | |
| CN103242146A (en) | Preparation method of cis-3-hexenal | |
| CN102146030A (en) | Method for preparing argine asprine | |
| CN102911154A (en) | Preparation method of water-soluble bromocresol purple | |
| CN102925974A (en) | Preparation method for high length-diameter ratio lead orthophosphate crystal whisker | |
| CN107556212B (en) | Method for preparing 2-diazo-acetoacetic acid p-nitrobenzyl ester | |
| CN107382898A (en) | A kind of energetic material and its synthetic method based on ANPZ precursor structures containing energy | |
| CN112279787A (en) | Post-treatment method for obtaining high-purity 2-hydroxyethyl urea | |
| CN105218480B (en) | A kind of preparation method of 1- (N- alkyl phenothiazinyl) -1- methyl (H) -2- substitutions Schiff |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |